78th MEETING OF

DRUGS TECHNICAL
ADVISORY BOARD (DTAB)
TO BE HELD ON
12th FEBRUARY 2018
AT 11.30 A.M.
IN NIRMAN BHAWAN,
NEW DELHI
 AGENDA INDEX
S. No. AGENDA ITEMS PAGE NO.

1. Action taken report for 77th DTAB meeting held on 16.06.2017 4

Consideration of the proposal for examination of cases of banning of 344

FDCS + 05 FDCS by DTAB/ Sub-Committee and send report to the
2. Central Government as directed by the Hon’ble Supreme Court of India 6
within six months from the date on which this judgment is received by the
DTAB
Consideration of the proposal for amendment of rule 96 under Drugs
3. & Cosmetics rules, 1945 for disclosure of prices at first point of 10
sale/price to trade (PTT)/ Ex-factory price or import price

Consideration of the proposal for notifying (I) Kamarajar port ltd.,

4. Chennai, Tamilnadu and (II) Mundra Port, Kutch, Gujarat; for import 11
/export of drugs/pharmaceuticals

Consideration of the proposal for exemption under para 15 of

DMR(OA), 1954 to communicate "fever" for creating public
5. awareness on management of fever associated with common self- 12
limiting conditions such as fever associated with common cold and
flu, dengue, chikungunya, fever associated with vaccination etc.
Consideration of the proposal regarding inclusion of separate form
6. for issuing test reports to other than manufacturers like the 13
procurement agencies and others
Consideration of the proposal to include Ultrasound equipments and
7. similar imaging equipments under the purview of Section 3 (b) (iv) of 14
the Drugs and Cosmetics Act, 1940 as Medical Devices
Consideration of the proposal to amend Drugs & Cosmetics Rules to
have Single Licensing Authority instead of multiple licensing
8. authorities having experience in manufacture or testing of drugs or 15
enforcement of provisions of the act for a minimum period of 10
years
Reconstitution of sub-committee of Drugs Technical Advisory Board
9. 16
on Homeopathy
Consideration of the proposal to clarify whether the Centchroman
(30mg) tablets to be exempted from the provisions of chapter IV of
10. 17
the D& C act and Rules under schedule K or to sell the remaining
strengths under schedule H of D& C rules
Consideration of the proposal for denotification of GSR 743(E) dated
10.08.1989 issued under section 26A for prohibition of all fixed dose
11. 18
combination injectable preparations containing synthetic Oestrogen
and progesterone
Consideration of the proposal to explore the feasibility of providing a
12. 20
separate shelf/rack for generic medicines in pharmacy

Page 2 of 33
S. No. AGENDA ITEMS PAGE NO.
Consideration of the proposal for amendment of Rule 127(2) of the
Drugs And Cosmetics Rules, 1945, so as to remove the ambiguity
13. 21
and scope of different interpretations in case of use of colours in
empty gelatine capsules (hard and soft)
Consideration of the proposal to amend Schedule D of the Drugs
and Cosmetics Rules, 1945 to provide exemption for
14. 23
radiopharmaceuticals from the provisions of the Chapter III of the
Drugs and Cosmetics Act, 1940
Consideration of the proposal for review of prophylactic doses
15. mentioned under Schedule ‘V’ of Drugs And Cosmetics Rules,1945 24
vis a vis the doses prescribed under FSS Act
Consideration of the proposal for amendment of Para 10.9 of
Schedule ‘M’ of Drugs and Cosmetics Rules, 1945 for waiver of
16. 25
requirement for vaccines manufactured using less than 60%
residual shelf-life period in the country
Consideration of the proposal to amend the Medical Devices Rules,
17. 2017- issue general clarification for smooth and uniform 27
implementation
18. Additional agenda (if any) with the approval of the Chair 33
19. Annexure- 1 to 6 34

Page 3 of 33
 AGENDA NO.1

ACTION TAKEN REPORTFOR 77thDTAB MEETING HELD ON 16.06.2017

AG.
AGENDA ISSUES ACTION TAKEN
NO.
Action taken report for 76th DTAB meeting
1. Approved
held on 31.01.2017
Consideration of the proposal to amend
Draft notification published vide G.S.R.
form 12-B of the Drugs And Cosmetics
No.1367 (E) dated 03.11.2017 and under
Rules for permit to import of small
2. finalization.
quantities of drugs for personal use for
longer periods instead of six months in
case of chronic diseases
Consideration of the proposal to amend Draft notification published vide G.S.R.
schedule H to include certain steroid No.1357 (E) dated 01.11.2017 and under
3. preparations which are misused mainly as finalization.
topical steroids leading to extensive tinea
infections
Consideration of the proposal to label iron The proposal is agreeable in principle and
tablets and polio drops distributed to the may be kept voluntary for multilingual
children under government programmes labelling where ever practical. Committee
with name and expiry date in Hindi also further opined that the proposal needs to be
4. considered in broader prospective for making
provision under the Drugs and Cosmetics
Rules, 1945 requiring the manufacturers of
drugs to provide Patient Information with the
drugs.

Consideration of the proposal to make a

provision under the Drugs And Cosmetics
Draft notification is under consideration by
Rules, 1945 for permission to sell /
Ministry.
5. distribute remaining quantities of unused
clinical trial batch of a biological drug
within its shelf life, if results of clinical trial
have been found satisfactory
Consideration of the proposal to exempt Draft notification published vide GSR
under Schedule-K for manufacturing of No.1368 (E) dated 03.11.2017.
6.
Oxygen 93%

Consideration of the proposal for

inclusion of “Stem Cells and Cell Based Draft notification is under consideration by
7. Products” under the definition of new Ministry.
drugs and its regulation under the Drugs
And Cosmetics Rules, 1945
8. Consideration of report of sub-committee The DTAB noted the report of the sub-

Page 4 of 33
AG.
AGENDA ISSUES ACTION TAKEN
NO.
of DTAB in respect of the directions of the committee and recommended that it should
Hon’ble high court of judicature of Patna be presented to the Director General of
for analyzing the components of Health Services for further consideration.
ingredients and their effect on human
body if consumed as food in respect of
the Neutraceutical products under
consideration in the Case of CWJC of
2425 of 2006
Consideration of the proposal for making
The DTAB recommended that details
the engagement of pharmacist having
giving full background objective of the
9. relevant qualification mandatory for blood
agenda should be placed before the Board
banks/blood storage centers
for consideration.

Consideration of proposal to amend

Drugs And Cosmetics Rules, 1945,
pertaining Part XB– Requirements for
The DTAB agreed with the proposal and
the collection, storage , processing and
required that the Chairman may further
distribution of whole human blood ,
10. discuss the issue with some experts in this
human blood components by blood banks
field for further consideration of notification
& Part XII B- Requirements for the
of draft rules.
functioning and operation of a blood bank
and/or for preparation of blood
components
Consideration of proposal to amend
Drugs And Cosmetics Rules, 1945
incorporating a provision for DTAB opined that the proposal does not
11.
Pharmacovigilance fee to be levied on the come under their purview.
marketing permission holder of new drugs
as well as other drugs
Consideration of the proposal to prohibit The matter has been placed before
antibody detection Rapid Diagnostic Directorate of National Vector Borne Disease
S-1 Tests for routine diagnosis of MALARIA to Control Programme (NVBDCP) for their
manufacture/ import and sale of in Indian expert comments.
market
Amendment in notification of BA/BE Draft notification is under consideration by
S-2 requirement from for “Oral Dosage Form” Ministry.
to “Oral Solid Dosage Form”
Measures for uniform
implementation of provisions of Drugs &
S-3 Agreed
Cosmetics Act And Rules throughout the
country

Page 5 of 33
 AGENDA NO. 2

CONSIDERATION OF THE PROPOSAL FOR EXAMINATION OF CASES OF

BANNING OF 344 FDCS + 05 FDCS BY DTAB/ SUB-COMMITTEE AND SEND
REPORT TO THE CENTRAL GOVERNMENT AS DIRECTED BY THE HON’BLE
SUPREME COURT OF INDIA WITHIN SIX MONTHS FROM THE DATE ON
WHICH THIS JUDGMENT IS RECEIVED BY THE DTAB

The Department Related Parliamentary Standing Committee (PSC) on Health

and Family Welfare had, in its 59th Report, observed that some State Licensing
Authorities had issued manufacturing licences for a very large number of FDCs
without prior clearance from CDSCO and this had resulted in the availability of many
FDCs in the market which have not been tested for efficacy and safety. The
Committee had also noted that this could put patients at risk.

The Parliamentary Standing Committee had also expressed the view that
those unauthorized FDCs that pose risk to patients and communities, such as a
combination of two antibacterials, need to be withdrawn immediately due to the
danger of developing resistance that would affect the entire population. DCG (I) had
requested all State/UT Drug Controllers to ask the concerned manufacturers in their
States to prove the safety and efficacy of such FDCs as had been licensed by SLAs
prior to 01.10.2012 without obtaining the approval of DCG (I) within a period of 18
months, failing which, such FDCs would be considered for being prohibited for
manufacture and marketing in the country.

In reply, CDSCO received approximately 6320 applications from

manufacturers for proving the safety and efficacy of these FDCs. On scrutiny, it was
observed that many FDCs are being manufactured by a number of applicants. With
the approval of the Ministry, CDSCO constituted 10 Expert Committees on
03.02.2014 for examining the safety and efficacy of these FDCs. These Committees
could, however, examine only about 295 applications. Subsequent to that the Central
Government appointed another Expert Committee to examine the matter. The
Committee was also assisted by eminent experts in different therapeutic areas from
premier Medical Institutions and hospitals.

The Expert Committee, after detailed examination and deliberations

recommended that some of these FDCs lacked therapeutic justification; were found
to be pharmacokinetically or pharmacodynamically incompatible; had abuse

Page 6 of 33
potential; or could lead to antibiotic resistance in the population. The Expert
Committee carried out a comprehensive review of the FDCs keeping in view the
contemporary scientific knowledge and expertise. On the basis of the
recommendations of the Expert Committee, the Government examined the matter
further and requested the Committee to provide specific reasons in respect of each
FDC that was found to be irrational. The Committee, accordingly reviewed the matter
further and finalized its recommendations. After careful consideration of the matter,
the Government issued show cause notices to all the manufacturers whose products
were found to be irrational and who had submitted their applications to the Central
Drugs Standard Control Organization. At the request of the manufacturers, additional
time of three months was given to them to respond to the show cause notices.
Thereafter, due consideration of the report and replies, the Government vide Gazette
Notifications S.O. Nos. 705(E) to 1048(E) dated 10.03.2016 prohibited the
manufacture for sale, sale and distribution for human use of 344 FDCs with
immediate effect in public interest as use of such FDCs was likely to involve risk to
human beings whereas safer alternatives to these drugs were available. The FDCs
that have been held irrational had been licensed by the State Licensing Authorities
without approval of the DCG(I). However, in case of a few of these FDCs, approval
had also been given by the DCGI.

Further, in pursuance of the action taken note on the 59th PSC report, based
on the examination by the Subject Expert Committee constituted by the Central
Government, the Government vide Gazette Notifications S.O. Nos.1851(E) to
1855(E) dated 08.06.2017 prohibited the manufacture for sale, sale and distribution
for human use of 5 FDCs with immediate effect in public interest

The Hon’ble Supreme Court of India in its Judgement dated 15.12.2017

pertaining to the issue of FDCs has directed DTAB and/or a Sub-Committee formed
by DTAB for the purpose, to have a relook into these cases.

The DTAB/ Sub-committee shall examine/deliberate these cases on the

parameters as laid down by Hon’ble Supreme Court of India in its Judgement as
follows:

“On the facts of these cases, a suggested course of action was stated by
learned counsel appearing on behalf of the petitioners/appellants. This course

Page 7 of 33
is that instead of now remitting the matter back to the Delhi High Court for an
adjudication on the other points raised in the writ petitions, the case of 344
FDCs that have been banned, plus another 5 FDCs that have been
banned, which comes to 349 FDCs, (barring 15 FDCs that are pre 1988
and 17 FDCs which have DCG(I) approval) pursuant to the Kokate
Committee report, by notifications of the Central Government under
Section 26A of the Drugs Act, should be sent to the DTAB, constituted
under Section 5 of the Drugs Act, so that it can examine each of these
cases and ultimately send a report to the Central Government.

In order that an analysis be made in greater depth, we, therefore, feel that
these cases should go to the DTAB and/or a Sub-Committee formed by the
DTAB for the purpose of having a relook into these cases. It is important,
however, that the DTAB/Sub-Committee appointed for this purpose will
not only hear the petitioners/ appellants before us, but that they also hear
submissions from the All India Drugs Action Network. The DTAB/Sub-
Committee set up for this purpose will deliberate on the parameters set
out in Section 26A of the Drugs Act, as follows:

First and foremost in each case, the DTAB/Sub-Committee appointed by it

must satisfy itself that the use of the Fixed Dose Combinations (FDC) in
question is likely to involve any one of the aforesaid three things:

(a) that they are likely to involve any risk to human beings or animals; or

(b) that the said FDCs do not have the therapeutic value claimed or purported
to be claimed for them; or

(c) that such FDCs contain ingredients and in such quantity for which there is
no therapeutic justification.

The DTAB/Sub-Committee must also apply its mind as to whether it is then

necessary or expedient, in the larger public interest, to regulate, restrict or
prohibit the manufacture, sale or distribution of such FDCs. In short, the
DTAB/Sub-Committee must clearly indicate in its report:

(1) as to why, according to it, any one of the three factors indicated above is
attracted;

Page 8 of 33
 (2) post such satisfaction, that in the larger public interest, it is necessary or
expedient to (i) regulate, (ii) restrict, or (iii) prohibit the manufacture, sale or
distribution of such FDCs.

The DTAB/Sub-Committee must also indicate in its report as to why, in case it

prohibits a particular FDC, restriction or regulation is not sufficient to control the
manufacture and use of the FDC. We request the DTAB/Sub-Committee to be
set up for this purpose to afford the necessary hearing to all concerned, and
thereafter submit a consolidated report, insofar as these FDCs are concerned,
to the Central Government within a period of six months from the date on
which this judgment is received by the DTAB.”

The list of 344 FDCs + 05 FDCs i.e. 349 FDCs is annexed as ANNEXURE-1.
The copy of Judgment of Hon’ble Supreme Court of India dated 15.12.2017 is
enclosed as ANNEXURE-2.

As per the order of Hon’ble Supreme Court of India dated 15.12.2017, DTAB
may examine the matter and devise the mechanism/method of communication to the
Appellants/Petitioners along with schedule for undertaking such exercise including
hearing from the Appellants and All India Drug Action Network (AIDAN), so that it
could be completed in 06 months time.

Page 9 of 33
 AGENDA NO. 3

CONSIDERATION OF THE PROPOSAL FOR AMENDMENT OF RULE 96 UNDER

DRUGS & COSMETICS RULES, 1945 FOR DISCLOSURE OF PRICES AT FIRST
POINT OF SALE/PRICE TO TRADE (PTT)/ EX-FACTORY PRICE OR IMPORT
PRICE
A proposal is received from Ministry to amend Rule 96 of Drugs and
Cosmetics Rules, 1945 to make it mandatory for the manufacturers/ importers to
disclose the first point sale price/ Price to Trade (PTT)/ ex-factory price or import
price of drugs on the label of packing.

A copy of the draft amendment on the said subject prepared and shown to
DGHS for his in-principle approval as the Chairman of DTAB before the draft
notification is published in the official gazette for inviting comments of
public/stakeholders. Copy of draft notification to amend rule 96 of Drugs &
Cosmetics Rules, 1945 is placed as ANNEXURE-3.

DTAB may kindly deliberate and give their views/comments/suggestions on

proposed amendment.

Page 10 of 33
 AGENDA NO. 4

CONSIDERATION OF THE PROPOSAL FOR NOTIFYING (I) KAMARAJAR PORT

LTD., CHENNAI, TAMILNADU AND (II) MUNDRA PORT, KUTCH, GUJARAT;
FOR IMPORT /EXPORT OF DRUGS/PHARMACEUTICALS

I) Several proposals were received for notifying Kamarajar Port Ltd.

(formerly known as Ennore Port Ltd.) for import /export of
drugs/pharmaceuticals as it is presently having five nos. of Terminals on
Operation, out of which, two are captive users, two are BOT’s and one
own Car Import/Export Terminals. The port is equipped to handle export
and import of Drugs and Cosmetics. The port is also provided with facilities
for handling of refrigerated containers with continuous power supply
through 150 refers plug points till the goods are cleared from the port. The
container terminal was operational with effect from June, 2017. Further,
this port was declared as Customs area under section 8(b) of the Customs
Act, 1962 for the purpose of loading/unloading of import and export cargo
or any class of such goods by customs, Chennai vide public notice No.
11/2001 dated 31.01.2001.
II) Mundra Port is located in the Gulf of Kutch region and has carved niche for
itself amongst shipping lines and trade by providing world class
infrastructure. The port has handled more than 100 MMT (2.73 Million
TEUs containers) of cargo in 2015-16 & 85 MMT (3 Million TEUs
container) of cargo in 2016-17(up to January-17). Mundra Port given
significant revenue earned by Customs on cargo handled, Mundra Port is
an important set-up for the department Rs. 6232.77 Crores (2015-16) and
Rs. 6683.06 Crores ( up to January 16-17) respectively.

Accordingly, it was recommended that Kamarajar Port Ltd. and Mundra Port
Ltd. may be permitted for import/ export of Drugs, Pharmaceuticals and Cosmetics
and may also be notified under rule 43A.

Therefore, DTAB may consider and give its suggestions in the matter.

Page 11 of 33
 AGENDA NO. 5

CONSIDERATION OF THE PROPOSAL FOR EXEMPTION UNDER PARA 15 OF

DMR(OA), 1954 TO COMMUNICATE "FEVER" FOR CREATING PUBLIC
AWARENESS ON MANAGEMENT OF FEVER ASSOCIATED WITH COMMON
SELF-LIMITING CONDITIONS SUCH AS FEVER ASSOCIATED WITH COMMON
COLD AND FLU, DENGUE, CHIKUNGUNYA, FEVER ASSOCIATED WITH
VACCINATION ETC.

Representations received regarding the exemption of advertisement under

Para 15 of Drugs and Magic Remedies (Objectionable Advertisements) Act, 1954, to
communicate “Fever” for creating awareness on management of Fever associated
with common Cold and Flu, Dengue, Chikungunya, Fever associated with
Vaccination etc. and role of Paracetamol in initial self-management of such
conditions.

It is stated that “Paracetamol” is already exempted under Schedule K of Drugs

& Cosmetics Rules, 1945, at Serial No. 13 vide GSR 1060 (E) dated 05.09.1986, as
household remedy from the provisions of Chapter IV of the Drugs & Cosmetics Act,
1940 and Rules thereunder which require them to be covered with a sale license
subject to certain conditions.

Representations received emphasized that the exemption of advertising will

enable the deployment of education programs designed to provide consumers with
information to foster an understanding of about “Fever”. Several references are
communicated regarding the exemptions under Para 15 of DMR (OA), 1954,
including the publication from the Ministry of Health and Family Welfare.

As it is a policy matter which is dealt by the Ministry accordingly the DTAB

may deliberate the issue regarding exemptions under Para 15 of DMR (OA), 1945.

Page 12 of 33
 AGENDA NO. 6

CONSIDERATION OF THE PROPOSAL REGARDING INCLUSION OF

SEPARATE FORM FOR ISSUING TEST REPORTS TO OTHER THAN
MANUFACTURERS LIKE THE PROCUREMENT AGENCIES AND OTHERS

Providing a separate Form on lines of Form 39 of Drugs & Cosmetics, Rules,

1945 for other than manufacturers like procurement agencies and other institutions
for carrying out tests on drugs, cosmetics and raw materials was deliberated in 51 st
DCC meeting held on 09.06.2017. This was also agreed in 77th DTAB meeting held
on 16.06.2017 as one of the points of Additional Agenda.

At present there is no provision in Drugs & Cosmetics Rules, 1945, for issue
of test reports for other than manufacturers like procurement agencies and others
except Form 39, which is meant for institutions carrying out tests on drugs,
cosmetics and raw materials used in their manufacture on behalf of licencees for
manufacture for sale or drugs or cosmetics.

As per Part XV (A), Rule 150E of D& C Rules, Form 39 is issued only to the
licenced manufacturers. Accordingly, a draft rule is prepared and enclosed as
ANNEXURE- 4.

DTAB may review the proposal for the suitable amendment in the D & C
Rules

Page 13 of 33
 AGENDA No. 7

CONSIDERATION OF THE PROPOSAL TO INCLUDE ULTRASOUND

EQUIPMENTS AND SIMILAR IMAGING EQUIPMENTS UNDER THE PURVIEW
OF SECTION 3 (b) (iv) OF THE DRUGS AND COSMETICS ACT, 1940 AS
MEDICAL DEVICES

The Central Supervisory Board (CSB), constituted under the Pre-conception

and Pre-natal Diagnostics Techniques Act (PC & PNDT Act), 1994 in its 22 nd
meeting held on 13th October, 2014 under the Chairmanship of Hon’ble HFM
recommended to include Ultrasound machines and its accessories under Section 3
of the Drugs and Cosmetic Act, 1940.

DTAB in its 70th meeting held on 18.08.2015, deliberated the agenda for
inclusion of Ultrasound equipments under the purview of Section 3 (b) (iv) of Drugs
And Cosmetics Act, 1940, so that Ultrasound equipments and similar imaging
equipments could be regulated for their manufacture and import after introducing the
Drugs and Cosmetics (Amendment Bill 2015) in the Parliament for comprehensive
provision for regulating medical devices in general.

Recently, Medical Device Rules, 2017 have been notified vide GSR 78(E)
dated 31.01.2017, coming into force with effect from 1st day of January, 2018 for the
regulation of medical devices. Therefore, proposal to include Ultrasound equipments
and similar imaging equipments under the purview of Section 3 (b) (iv) of the Drugs
and Cosmetics Act, 1940 as Medical Devices is submitted for consideration of DTAB
in the light of Pre-conception and Pre-natal Diagnostics Techniques Act (PC & PNDT
Act), 1994.

DTAB may kindly deliberate the issue and give its recommendation on the
matter.

Page 14 of 33
 AGENDA NO. 8

CONSIDERATION OF THE PROPOSAL TO AMEND DRUGS & COSMETICS

RULES TO HAVE SINGLE LICENSING AUTHORITY INSTEAD OF MULTIPLE
LICENSING AUTHORITIES HAVING EXPERIENCE IN MANUFACTURE OR
TESTING OF DRUGS OR ENFORCEMENT OF PROVISIONS OF THE ACT FOR A
MINIMUM PERIOD OF 10 YEARS

DCC in its 51st meeting held on 09.06.2017 deliberated and taken a

consensus opinion that minimum experience required for Licensing Authority related
to manufacturing and sale of drugs should be raised to minimum of 10 years
regulatory experience instead of existing 5 years experience to be a Licensing
Authority.

Further this matter was placed before DTAB in its 77 th meeting held on
16.06.2017 and agreed by the members.

DTAB may deliberate and give its suggestions in the matter for necessary
amendments in the rules.

Page 15 of 33
 AGENDA NO. 9

RECONSTITUTION OF SUB-COMMITTEE OF DRUGS TECHNICAL ADVISORY

BOARD ON HOMEOPATHY

Ministry of AYUSH vide its F. No. K-11022/01/2014 HPC) dated 27.07.2017

informed to re-constitute the sub-committee of DTAB on Homeopathy.

The sub-committee of Drug Technical Advisory Board on Homeopathy was

constituted on 18.08.2015 and under terms of reference it was mentioned that the
tenure of the sub-committee shall be of two years. The term of the sub- committee
therefore expired on 17.08.2017.

In view of the above, DTAB may consider for reconstitution of the sub-
committee or for extension of the tenure of the existing sub-committee.

Page 16 of 33
 AGENDA NO. 10

CONSIDERATION OF THE PROPOSAL TO CLARIFY WHETHER THE

CENTCHROMAN (30MG) TABLETS TO BE EXEMPTED FROM THE
PROVISIONS OF CHAPTER IV OF THE D& C ACT AND RULES UNDER
SCHEDULE K OR TO SELL THE REMAINING STRENGTHS UNDER
SCHEDULE H OF D& C RULES

Ormeloxifene (also known as Centchroman) is one of the selective estrogen

receptor modulators, or SERMs, a class of medication which acts on the estrogen
receptor. It is best known as a non-hormonal, non-steroidal oral contraceptive which
is taken once per week. In India, Centchroman tablets 30mg and 60mg have been
available since the early 1990s, and it is currently manufactured and marketed by the
following manufacturers:

S. NO MANUFACTURER STRENGTH BRAND NAME INDICATION

30 mg Saheli / Novex oral contraception
1. Hindustan Latex Ltd.,
Trivandrum
60 mg Novex –DS Dysfunctional uterine bleeding
2.

Torrent 30 mg Centron oral contraception

3.
Pharmaceuticals Ltd,
Ahmedabad 60 mg Sevista Dysfunctional uterine bleeding
4.

Centchroman Tablet 30 mg was incorporated in Schedule K of the Drugs &

Cosmetics Act, 1940 and Rules, 1945 vide G.S.R 730(E) dated 10 th Dec, 1991, to
provide exemption of requirements for sale licence.

However, Centchroman was incorporated in Schedule H of Drugs and

Cosmetics Act, 1940 and Rules, 1945 vide G.S.R 160(E) dated 16 th Mar, 2006,
indicating that all formulations of Centchroman is required to be sold by retail on the
prescription of the Registered Medical Practitioner only.

Now, representation has been received from a manufacturer regarding

clarification whether the manufacturers can continue to sell this product as OTC
following Schedule K norms or to sell the product by retail on the prescription of the
Registered Medical Practitioner only as per Schedule H.

In view of the above, in order to allow marketing of Centchroman tablets 30

mg as OTC with exemption of sale licence under Schedule K, the Schedule H in
respect of Centchroman may need to be amended suitably.

DTAB may deliberate the issue and give recommendations.

Page 17 of 33
 AGENDA NO. 11

CONSIDERATION OF THE PROPOSAL FOR DENOTIFICATION OF G.S.R 743(E)

DATED 10.08.1989 ISSUED UNDER SECTION 26A FOR PROHIBITION OF ALL
FIXED DOSE COMBINATION INJECTABLE PREPARATIONS CONTAINING
SYNTHETIC OESTROGEN AND PROGESTERONE

Earlier all Fixed Dose Combination injectable preparations containing

synthetic Oestrogen and Progesterone were prohibited for manufacture for sale, sale
and distribution in the country vide GSR No. 743(E) dated 10.08.1989. A
representation has been received from one of the manufacturers for revocation of
the above notification for FDC of Medroxyprogesterone Acetate + Estradiol
Cypionate (cyclofem) injection from list of banned drugs.
The same was deliberated earlier by NDAC (Reproductive and Urology) on
17.09.2013 and the committee recommended that all FDC injectable preparations
containing synthetic Oestrogen and Progesterone were prohibited in the country,
most probably due to report of misuse of such preparations for pregnancy detection.
At present, chances of such misuse are insignificant as at present many pregnancy
detection kits which are very sensitive and various means for satisfactory
contraception are available. A copy of recommendations of the NDAC (Reproductive
and Urology) meeting held on 17.09.2013 is enclosed at ANNEXURE - 5.
ICMR has also conducted the clinical trial with the Cyclofem in 1275 subjects
who were followed up for 10934 women- months of use. The clinical data has been
found satisfactory. Available data shows that FDC injectable preparations containing
synthetic Oestrogen and Progesterone are not associated with change in Bone
Mineral Density. Therefore the committee recommended considering revocation of
banning of the FDC injectable preparations containing synthetic Oestrogen and
Progesterone by appropriate authority. The committee recommended the grant of
permission of clinical trial of Cyclofem and Norethisterone Enanthate (NET-EN)
subject to the following conditions:

1. The study should be titled as extended phase III clinical trial.

2. The study should be conducted at multispecialty hospitals having
emergency facilities and institutional ethics committee registered with
CDSCO.
3. Details of such sites along with undertaking by the investigators as per
appendix VII of Schedule Y should be submitted.

Page 18 of 33
 4. Informed consent document as per appendix V of schedule Y should be
submitted.
5. Undertaking as per Rule 122DAB for compensation and providing medical
management as per the Rule in case of injury/death in clinical trial.
6. Denotification of the banning of Cyclofem i.e. Fixed Dose Combination
injectable preparations containing synthetic Oestrogen and Progesterone
7. The recommendation may be placed before DTAB for further
consideration. (Dr. Sunita Mittal and Dr. Lakbir Dhaliwal did not take part in
decision making process due to conflict of interest).

This proposal was earlier deliberated in 65th DTAB held on 25.11.2013 and
DTAB recommended that An Expert Committee consisting of at least three
Gynecologists, three endocrinologists, Dr. Anoop Mishra and Dr. Y. K. Gupta, HOD,
Department of Pharmacology, AIIMS, New Delhi under the Chairmanship of DGHS
may be constituted to examine the essentiality of the clinical trial as well as the
requirement, if any, of the amendment of entry number 27 in respect of the FDC of
injectable preparations containing synthetic oestrogen and progesterone, in the
context of present day knowledge. However, no further proceeding took place in the
matter. A copy of minutes of 65th DTAB is enclosed as ANNEXURE- 6.

In view of above, the DTAB may kindly give their recommendations in respect
of denotification of G.S.R 743(E) dated 10.08.1989 issued under Section 26A for
prohibition of all FDC injectable preparations containing synthetic Oestrogen and
Progesterone.

Page 19 of 33
 AGENDA NO. 12

CONSIDERATION OF THE PROPOSAL TO EXPLORE THE FEASIBILITY OF

PROVIDING A SEPARATE SHELF/RACK FOR GENERIC MEDICINES IN
PHARMACY

Issue of exploring to keep a separate shelf / rack of generic medicines in

every pharmacy so as to promote the availability of “Generic Medicines” was
deliberated in 52nd DCC held on 18-09-2017 and agreed to the proposal.
Similar provisions are also exists under Rule 65, clause (12) for Schedule X
drugs and clause (20) for veterinary medicines. Accordingly, a provision under Rule
65 may need to be incorporated in Rule 65 as clause (22) in D & C Rules. A draft
prepared in this respect is given below:

In the Drugs and Cosmetics Rules, 1945, in Rule 65, after clause (21), the
following clause shall be inserted namely-
“(22) The licensee shall maintain a separate rack / shelf reserved solely
for the storage of “Generic Medicines” in a part of the premises
separated from other medicines.”.

In view of above, the DTAB may kindly deliberate and give their
recommendations to keep a separate shelf / rack of generic medicines in every
pharmacy so as to promote the availability of “Generic Medicines” in Rule 65 of
Drugs and Cosmetics Act, 1940 and Rules, 1945 made thereunder.

Page 20 of 33
 AGENDA NO. 13

CONSIDERATION OF THE PROPOSAL FOR AMENDMENT OF RULE 127(2) OF

THE DRUGS AND COSMETICS RULES, 1945, SO AS TO REMOVE THE
AMBIGUITY AND SCOPE OF DIFFERENT INTERPRETATIONS IN CASE OF USE
OF COLOURS IN EMPTY GELATINE CAPSULES (HARD AND SOFT)

Representations have been received from various State Drugs Controllers

that the Government Analysts of various States declaring the samples as of
Standard Quality with a note that it does not meet the requirement of labelling (as
name of approved colour used in the empty capsule shell is not mentioned on the
label), thus contravening the provision of rule 127(2) of Drugs & Cosmetics Rules,
1945.
Drugs & Cosmetics Rules, 1945, rule 127(2) specifies that

“The label on the container of a drug containing a permitted colour shall

indicate the common name of the colour.”

However, at the same time it is also true that there is more number of repeated
manufacturers who are also not mentioning the name of the colours used in the
empty capsule shell and as a practice writing the common statement on the label as
“approved colours used in capsule shell”.

It was felt that, whether the Government Analyst(s) is/are empowered to put
such a note that sample does not meet the requirement of labelling (“as name of
approved colour used in the empty capsule shell is not mentioned on the label”
instead a statement of “approved colours used in capsule shell”.) though the sample
is of standard quality for the reasons “the sample conforms to declared formula on
the basis of tests done” if so, whether it attract the administrative action or legal
action. This matter was referred to a sub-committee and following recommendations
were suggested:
1. Rule 127(2) provides that the labelling on the container of the drug
containing permitted colours shall indicate common name of the colour.
2. Empty Gelatine Capsules were included as drug in the definition of Drugs
in 1982.
3. Thereafter the issue of declaring colour on the label of the empty gelatine
capsule was discussed in DCC meeting held at New Delhi on 22 nd

Page 21 of 33
 September, 1983. In the said meeting it was decided that “ In the
manufacture of gelatine capsule colours permitted for manufacture of drug
should be used and label need not indicate the name of colour added as
more than one colour are quite often used.”
4. Monograph of gelatine capsules shell is included in IP Monograph 2014,
Page 1848 and 1849. In the labelling of monograph it is provided that the
labels state that only permitted colours, if any has to be declared.
5. In labelling requirements under Food Safety and Standards Act, 2006 it is
necessary to declare that permitted colour used. It is not necessary to
declare name and specific colour.
6. It is noted that Rule 127 was inserted under S.O. 289 dtd.20/12/1972
(w.e.f. 03/02/1973). Rule 96 was substituted by GSR 19 dtd.15/12/1977
(w.e.f. 07/01/1978). However, Rule 96 does not contain provision for
declaring colours.
7. In view of the decision taken by the DCC and having regard to the fact that
empty gelatine capsules or soft gelatine capsules are not active ingredient,
but are used as vehicle for providing active ingredient (Drugs) to the
patient and labelling directions under the monograph, it is felt that insisting
declaration of colour used in capsule shell will be considered as not
consistent with spirit of law.

DTAB may please consider the proposal and give its recommendations.

Page 22 of 33
 AGENDA NO. 14

CONSIDERATION OF THE PROPOSAL TO AMEND SCHEDULE D OF THE

DRUGS AND COSMETICS RULES, 1945 TO PROVIDE EXEMPTION FOR
RADIOPHARMACEUTICALS FROM THE PROVISIONS OF THE CHAPTER III OF
THE DRUGS AND COSMETICS ACT, 1940

DTAB in its 76th meeting held on 31st January 2017, deliberated the issue
regarding providing exemption for import of radiopharmaceuticals under Schedule D
of Drugs and Cosmetics Rules, 1945 and referred to Atomic Energy Regulatory
Board (AERB), Mumbai for their opinion for having holistic approach in the matter.
In response to this the AERB suggested that the decision regarding
exemption for import of radiopharmaceuticals as drug under the Drugs and
Cosmetics Act and the Rules promulgated thereunder rests with CDSCO. However,
they assured for continued coordination and support in having holistic approach in
the matter.
Under the Drugs and Cosmetics Rules, 1945, exemption has been provided
at Serial No 20, under Schedule K from the provisions of the Chapter IV of the Act
and the rules made there under. As such radiopharmaceuticals are not subjected to
regulatory controls in respect of their manufacture and sale. It is however observed
that no such exemption is provided for the radiopharmaceuticals imported into the
country.
In view of this it is proposed to provide exemption under Schedule D from the
provisions of Chapter III for radiopharmaceutical products imported into the country.

Class of drug Extent and conditions of exemption

“10. Radiopharmaceuticals All provisions of chapter III of the Act and Rules
made there under”

DTAB may please consider the proposal and give its recommendations.

Page 23 of 33
 AGENDA NO. 15

CONSIDERATION OF THE PROPOSAL FOR REVIEW OF PROPHYLACTIC

DOSES MENTIONED UNDER SCHEDULE ‘V’OF DRUGS AND COSMETICS
RULES VIS A VIS THE DOSES PRESCRIBED UNDER FSS ACT

A proposal has been received from FSSAI proposing that Drugs and
Cosmetics rules may be amended to delete the preparations containing the
prophylactic doses under Schedule ‘V’ considering the provisions of doses under
Section 22 of FSS Act especially products formulated in Tablets, Capsules, Liquids,
etc. meant for oral administration.
As per Section 22 of FSS Act, 2006 it is evident that the products in drug type
matrix (i.e. Tablets, capsules, etc.) covered under FSS Act which is containing
vitamins below RDA also falls under prophylactic and some of the therapeutic doses
prescribed in schedule V of the Drugs and Cosmetics Rules.
Secondly, FSSAI has also proposed for amending the Schedule K (10) for
revising the scope of substances which are used both as articles of food as well as
drugs so that same are exempted from the provisions of Chapter IV of D&C Act and
Rules made there under.
Accordingly, DCC in its 52nd DCC meeting held on 18.09.2017 deliberated the
proposal and recommended that a provision may be incorporated in Drugs and
Cosmetics Rules, 1945 especially in Sch ‘V’ and Sch ‘K’ to exclude multivitamin
preparations containing vitamins in a strength which is lower than Recommended
Daily Allowance (RDA) for Indians as recommended by ICMR and FSSAI, from the
provisions of Drugs and Cosmetics Rules, 1945.

DTAB may discuss the issue and give further recommendations so that
necessary amendment may be made under schedule ‘V’ as well as under schedule
K (10) respectively considering the provisions under FSS Act.

Page 24 of 33
 AGENDA NO.16

CONSIDERATION OF THE PROPOSAL FOR AMENDMENT OF PARA 10.9 OF

SCHEDULE ‘M’ OF DRUGS AND COSMETICS RULES, 1945 FOR WAIVER OF
REQUIREMENT FOR VACCINES MANUFACTURED USING LESS THAN 60%
RESIDUAL SHELF-LIFE PERIOD IN THE COUNTRY

Representation has been received from Shantha Biotechnics Pvt. Ltd.

Hyderabad for waiver of Para 10.9 of Schedule M in case of manufacturing of
vaccines using import of bulk concentrated vaccine components whose residual
shelf life is less than 60% when they used in the formulation which is contravening
the existing provision in Para 10.9 of Schedule M.

The firm has submitted that for import and use of Inactivated Poliomyelitis
Vaccine (IPV) bulk (concentrated trivalent) batches with less than 60% residual shelf
life period for formulation and filling of Inactivated Poliomyelitis Vaccine IP, Trivalent
stating that as recommended by Annexure 3 of WHO TRS 962 Guidelines on
stability evaluation of Vaccines, (Para 5.3) the stability of the characteristics of a final
product should be guaranteed during the whole shelf-life, irrespective of the age of
the intermediates at the time they are used in the production process.

The firm was earlier issued NOC from DCGI Office for the import and use of
Inactivated Poliomyelitis Vaccine bulk (concentrated trivalent) (IPV) batches with less
than 60% residual shelf-life period for formulation and filling of Inactivated
Poliomyelitis Vaccine IP, Trivalent with a condition to comply the provision as laid
down in Para 10.9 of PART 1 of Good Manufacturing Practices for Premises and
Materials of Schedule M of Drugs and Cosmetics Rules 1945. Accordingly, the firm
had imported IPV bulk batches with less than 60% residual shelf life under Form-11
from M/s Sanofi Pastuer, France and manufactured 6 batches of Inactivated
Poliomyelitis Vaccine IP, Trivalent using residual shelf-life period of 6.3%, 20.5%,
21.6%, 6.3%, 20.5% and 21.6% respectively.

The firm has reported that these Inactivated Poliomyelitis Vaccine batches
were found to be stable up to 24 months shelf life period when stored at 2 to 8ºC, 6
months at 25±2ºC and 7 days at 37±2ºC. The firm has also stated that drug product
batches manufactured with less residual shelf life bulks are stable up to the shelf-life

Page 25 of 33
period i.e. 36 months and submitted the stability data up to 24 months when stored
at 2 to 8ºC against the claimed shelf life.

In view of above, DTAB may deliberate as whether such type of vaccine bulks
with less than 60% residual shelf life, imported may be permitted to be used for
manufacturing/formulation of vaccines (product licences) with the expiry of 2 years
keeping the view of above stated rule position and suggest any suitable amendment
required exclusively for vaccines.

Page 26 of 33
 AGENDA NO.17

CONSIDERATION OF THE PROPOSAL TO AMEND THE MEDICAL DEVICES

RULES, 2017- ISSUE GENERAL CLARIFICATION FOR SMOOTH AND UNIFORM
IMPLEMENTATION

The Ministry of Health & Family Welfare, Government of India has notified the
Medical Devices Rules 2017 vide G.S.R. 78(E) dated 31.01.2017 under the
provisions of the Drugs and Cosmetics Act, 1940.

Said rules are effective from 01.01.2018 to regulate the Clinical Investigation,
Manufacture, Import, Sale and Distribution of the medical devices in the country.

Further, representation received from the Industry/ Stakeholders/ Associations

regarding the consideration of the proposal to amend in the Medical Device Rules,
2017.

Accordingly, following agendas are placed below for the consideration of DTAB:

1) CONSIDERATION OF THE PROPOSAL TO DEFINE PATHWAY RELATED TO

DISPOSAL OF APPLICATIONS RELATED TO CLAA RECEIVED AFTER 31ST
DECEMBER 2017

Medical Devices Rules 2017 have been implemented from 1st January 2018.
Further, this Directorate has received applications for Additional products
endorsement, Grant of manufacturing licence in form 28 and renewal applications
in Hard copy after 31st December 2017. (List attached for the reference)

It is pertinent to mention that some applications of endorsement has

forwarded by various State Licensing Authorities before 31.12.2017 but received
by this office after 31.12.2017.

It is proposed to define pathway related to disposal of applications related to

CLAA received after 31st December 2017.

In this regard, it is proposed that if application is done& joint inspection is

carried out and recommended by State Licensing Authority with effective date
earlier to 31.12.2017, it may be considered for signing by DCG (I ) effective from
that date (undertaking clause).

In case of renewal of manufacturing licenses, if firm has applied with fees it

used to be considered as deemed renewed till orders are passed as per earlier
rule of 75 and 77 of Drugs & Cosmetics Rules, 1945. If no orders are passed, such
license shall be considered valid till 31.07.2018 in the light of rule 97 of MDR-2017
& clarification in this regard may be issued to bring clarity & uniformity of
implementation.

DTAB may deliberate & give its recommendation

Page 27 of 33
2) CONSIDERATION OF THE PROPOSAL RELATED TO ENDORSEMENT OF
ADDITIONAL PRODUCTS IN OLD REGISTRATION CERTIFICATE/ IMPORT
LICENSE/ MANUFACTURING LICENCE

As per the Rule 97, the manufacturing licenses as well as import licenses
which have validity post January 2018 will remain valid till their expiry. However,
there is not adequate provision in the Rules for endorsements of additional
products in these licenses. This is an operational bottleneck for the manufacturers
and importers.

Stakeholders have requested to make provisions in the old SUGAM for

endorsement of additional product at discounted fees as compared to the fees in
New MDR as they will be getting a limited validity. Alternately, if discounted fee is
not a viable option for the CDSCO. Further, Industry suggested for a provision to
apply for endorsement under the new Rules, on the new portal, with approvals
having perpetual validity as per Medical Device Rules 2017.Plant Master File
documentation and applicable fee should not be required in this scenario as the
site is already registered in India.

It is stated that validity of manufacturing license (as per Rule 29) and import
license (as per rule 37) remain valid in perpetuity, subject to payment of licence
retention fee. Further, in this regard, it is informed that firm can get endorsement in
old Registration Certificate/ Import License/ Manufacturing licence; however there
is no provision for discounted fee. Further, it is proposed that firm may apply for
addition of products in existing Registration Certificate/ Import License/
Manufacturing licence provided that documents and fees will be submitted as per
Medical Device Rules, 2017.

DTAB may deliberate & give its recommendation.

3) CONSIDERATION OF THE PROPOSAL TO AMEND ENVIRONMENTAL

REQUIREMENTS IN RESPECT OF MANUFACTURING FACILITY AS
SPECIFIED IN THE FIFTH SCHEDULE OF MEDICAL DEVICES RULES, 2017

It has been pointed out and informed by stakeholders that the Fifth Schedule
[for rule 20 (3), 20(5), 20(8), 22 (j)] (Quality Management System for Medical
Devices and in vitro diagnostic medical devices), Annexure A – Environmental
Requirement for medical devices and in-vitro diagnostic medical devices, has
prescriptive requirements of manufacturing environmental conditions, which is not
in harmony with International (IMDRF) regulations.

This Directorate has received suggestions from Industry/ Stakeholders. They

have stated that this is leading to a situation that all indigenous manufacturers
need to make alterations to the manufacturing facilities which are not in line with
global manufacturing conditions. The manufacturing conditions have been

Page 28 of 33
prescribed based on the extrapolation of drug manufacturing condition which is not
suitable for medical devices.

Hence, the environmental conditions in Fifth Schedule of the Medical Device

Rules should be removed from the Fifth Schedule or should be redrafted as
guidance rather than as statutory requirements.

Further, Surgical Dressings Manufacturers Association has also made

representation regarding the amendment for environmental requirements in
respect of manufacturing facility for surgical dressings as specified in the
Annexure- A of the Fifth Schedule of Medical Devices Rules, 2017.

In their representation, they have stated that, presently the manufacturers of

surgical dressings complying the requirement as specified in “Schedule M” of
Drugs & Cosmetics, Act, 1940 and Rules 1945 by arranging neat, clean & dust
and free environment for the manufacturing of surgical dressings.

The “Schedule M” does not prescribe the specific environmental requirement

for the manufacturing of Surgical Dressings. However, in the Medical Devices
Rules, 2017, fifth Schedule specified the specific environmental requirement for
the type of operation as per ISO Class as under:

Name of the device Type of operation ISO Class(At rest)

Surgical Dressings Weaving 9
Assembly and Gauzing 9
Final primary packing 9

In this regard, the association members have raised concerns for their inability
to maintain environmental requirement to have an ISO Class 9 room for weaving,
assembly and gauzing and final primary packing as they are small and tiny
manufacturers.

Further, the representatives of the associations were called for personal

hearing by CDSCO in order to have detailed deliberation in the matter where the
stakeholders requested to put these conditions in abeyance.

Accordingly, following changes are proposed to be made in Annexure A of the

fifth Schedule of MDR, 2017 regarding the environmental requirement of
manufacturing of surgical dressings:

a) Annexure A of the fifth schedule of said rules shall be deleted and treated as
guidance document.
In this document
I. Instead of surgical dressing, sterile surgical dressing to be substituted.
II. Weaving and Assembly and Gauzing to be replaced by final primary
packing for sterile surgical dressings.
III. Similarly, for condoms neat & clean environment free from dust etc. shall
be replaced instead of 5 µ filter.

Page 29 of 33
 DTAB may deliberate & give its recommendation.

4) CONSIDERATION OF THE PROPOSAL TO DEFINE PATHWAY TO SUBMIT

ABRIDGED APPLICATIONS (WITH TRUNCATED DOCUMENTATION) FOR
SUBSEQUENT IMPORT LICENSE APPLICATIONS

Industry/ stakeholders requested for a defined pathway to submit abridged

applications (with truncated documentation) for subsequent import license
applications for the site and products already approved under MD-15.

In this regard, it is proposed that abridges pathway may be accepted provided

that an undertaking from the manufacturer should be submitted stating that No
change have been made in the document submitted earlier while registering with
earlier agent.

DTAB may deliberate & give its recommendation.

5) CONSIDERATION OF THE PROPOSAL FOR THE DIGITAL SIGNATURE,

WHEREVER APPEARING IN THE RULES, MAY BE MADE OPTIONAL

In the Medical Devices Rules, 2017 submission of some applications required

Digital signature. Further, in case of technical error, it is proposed to use routine
signature for the submission of application form.

It is requested by stakeholders that Digital Signature, wherever appearing in

the rules, may be made optional by amending the rules.

DTAB may deliberate & give its recommendation.

6) CONSIDERATION OF THE PROPOSAL TO ADD PROVISIONS IN RESPECT

OF THE WAIVER OF CLINICAL PERFORMANCE EVALUATION FOR IVDs, IN-
LINE WITH WAIVER GIVEN FOR MEDICAL DEVICE UNDER RULE 63 OF
MEDICAL DEVICES RULES, 2017

Rules 63 of the Medical Device Rules (Chapter VIII) – Import or Manufacture

Medical Device Which Does Not Have Predicate Device - regarding Permission to
import or manufacture medical device which does not have its predicate device.

There are provisions that clinical investigation be waived off if the device has
2 years of marketing experience in UK, USA, Australia, Canada or Japan.
However, a corresponding provision is missing for Rule 64 – Permission to import
or manufacture new in-vitro diagnostic medical device.

In view of the above, it is proposed to add identical provisions in rule 64 for

IVD devices.

DTAB may deliberate & give its recommendation.

Page 30 of 33
7) CONSIDERATION OF THE PROPOSAL FOR THE SUBMISSION OF
APPLICATIONS OF MEDICAL DEVICES AND IVDS THROUGH OFFLINE
MODE

All applications for obtaining licenses will be made through online portal of the
Central Government. New Medical Device portal is functional for uploading the
applications for Import License, Registration and Manufacturing License etc.

It is proposed that, in case of failure of online portal for submission of

applications for import and manufacture, there should be a provision to accept &
process application in offline mode under MDR 2017 in order to dispose of the
applications.

8) CONSIDERATION OF THE PROPOSAL TO INCREASE THE TIMELINE OF

SUSAR REPORTING IN MDR,2017

As per the said rules, Serious Unexpected Serious Adverse

Reaction (SUSAR) need to be reported within 15 days of occurrence where as
SUSAR will be confirmed only after detailed investigation of the incident. This will
not be completed within 15 days. Industry/ Stakeholder suggested that the timeline
of SUSAR reporting need to be at-least 45 days of occurrence.

Further, it is proposed to increase the timeline of SUSAR reporting.

9) CONSIDERATION OF THE PROPOSAL TO INCREASE THE TIMELINE OF ANY

REGULATORY ACTION TAKEN ACROSS THE WORLD

As per the said rules, any regulatory action taken across the world need to be
reported within 15 days of such action and the industry feel that it is too short a
time frame for the member companies to comply with the requirement. Industry/
Stakeholder suggested that the timeline may be raised to 45 days from 15 days.

Further, it is proposed to increase the timeline for the same.

10) CONSIDERATION OF THE PROPOSAL TO INCLUDE MEDICAL DEVICE

EXPERT IN DTAB

Industry/ stakeholders requested for the seat for Medical device sector/
industry in Drug Technology Advisory Board (DTAB). It is proposed to include
medical device expert whenever medical device related proposals are being
discussed.

Page 31 of 33
11) IMPORT LICENSE REQUIREMENTS SHOULD NOT BE MANDATORY FOR
COMPONENTS THAT ARE IMPORTED FOR FURTHER PROCESSING BY
MEDICAL DEVICE /PHARMACEUTICAL MANUFACTURERS WITH VALID
MANUFACTURING LICENSE

Industry/ stakeholders requested that Import license requirements should not

be mandatory for Components i.e. manufacturing that are imported for further
processing by medical device/pharmaceutical manufacturers with valid
manufacturing license. One time NOC to be issued for such components on
submission of valid manufacturing license to the CDSCO. If any license is issued
previously for import of components for further processing of Medical devices then
it should be treated only as a trading license.

DTAB may deliberate & give its recommendation for issue of clarification.

12) WHEN MEDICAL DEVICES WHICH ALREADY EXIST IN THE INDIAN MARKET
FOR USE ARE BROUGHT IN FUTURE UNDER REGULATION, THEN SUCH
DEVICES SHALL NOT BE A NEW MEDICAL DEVICES.

It is requested by stakeholders to clarify as per the present rules, the definition

of Investigational medical devices and Predicate devices amounts to those devices
which are not approved by CDSCO. However, there are many devices in the
country which are not regulated and when they are brought under regulation will
fall under the ambit of investigational medical device as well as that we will not be
leverage it as predicate device. This anomaly need to be addressed such that
when new devices are brought under regulation, manufacturers should not be
asked to take the path of investigational medical device.

DTAB may deliberate & give its recommendation for amendment of rule.

13) CONSIDERATION OF THE PROPOSAL FOR NOTIFICATION OF ORGAN

PRESERVATIVE SOLUTION AS MEDICAL DEVICE UNDER SECTION 3(b) (iv)
OF THE DRUGS AND COSMETICS ACT, 1940

Organ preservative solution are intended to be used for flushing and cold
storage of organs like heart, lungs, kidney, liver and pancreas at the time of
removal from donor in preparation for storage, transportation and eventual
transplantation in to the recipient. The solution consists of Glutathione, Mannitol,
Lactobionic acid, glutamic acid, sodium Hydroxide, Calcium Chloride 2H 2O,
Potassium Chloride, Magnesium Chloride, Histidine, Water for Injection etc. in
order to achieve a specific osmolarity required for organ preservation.

This office has received various applications on the regulatory status of Organ
Preservative solution. This office has given clarifications to the applicant that the
same is not notified under Section 3 (b) (iv) of Drugs and cosmetic Act 1940 and
therefore not regulated as Medical Devices. The clarification issued is annexed for
reference. However, the same is regulated as Drugs and permission for same has

Page 32 of 33
given by Import Division. It may however be stated that, the Organ Preservative
Solutions are regulated as medical Devices in many countries.

It is therefore proposed, that the Organ Preservative Solution may be notified

under Section 3 (b) (iv) of Drugs and Cosmetic Act 1940 so that the same may be
brought under the regulation.

In view of the above, the DTAB may kindly consider the said proposals and
recommended for amendment in the Medical Devices Rules, 2017 and inclusion of
Nebulizer, Glucometer and Organ preservative solution under Section 3 (b) (iv) of
Drugs and Cosmetics Act 1940.

AGENDA NO.18

Additional agenda (if any) with the approval of the Chair.

Page 33 of 33
 Annexure -1

Annexure-I

List of 344 FDCs + 05 FDCs already prohibited for manufacutre and sale through gazette notifications under Section 26A of Drugs & Cosmetics Act 1940 by the Ministry
of Health and Family Welfare for further deliberation by DTAB/Sub-committee as per the Judgement given by Hon'ble Supreme Court of India on 15.12.2017

S. No. Name of Drug Recommendation under Second Assessment by the Kokate Committee (Dated 16.04.2015) Prohibition
Notification No.
1 Aceclofenac + Paracetamol a, S.O. 705 (E)
+ Rabeprazole 1.There is pharmacokinetics incompatibility among the three drugs, as the dosing intervals are BD for
aceclofenac, OD for rabeprazole and TDS/QID for paracetamol.
2.The FDC is not approved anywhere in the world
3.The literature regarding safety and efficacy of this combination is not available in Pubmed & Google scholar

2 Nimesulide + Diclofenac a, S.O. 706 (E)

1. Nimesulide in combination has potential of misuse and have documanted safety concern.
2. No additional advantage but hepatotoxic potential of nimesulide and adverse effects add up.
3.Pharmacodynamically irrationale FDC as both have same mechanism of action (both drugs acting on the same
enzyme). Thus, combining two NSAIDs does not and cannot improve the efficacy of treatment. It only adds to
the cost of therapy and more importantly, to the adverse effects

Chandler S. Gautam, Lekha Saha. Fixed dose drug combinations (FDCs): rational or irrational: a view point Br
J Clin Pharmacol / 65:5 / 795–796.
Kasarla Raju, A. Elumalai2, Eddla Srid. IRRATIONAL DRUG COMBINATIONS. Vol 3|Issue 2| 2013 | 52-56.

3 Nimesulide + Cetirizine a, S.O. 707 (E)

+Caffeine 1. Nimesulide in combination has potential of misuse in indications for allergic conditions.
2. Nimesulide has documanted safety concern.

4 Nimesulide +Tizanidine a, S.O. 708 (E)

1. Nimesulide in combination form has potential of misuse.
2. The FDC is pharmacokinetically incompatible as both have different dosing schedule.
3. Safety concern with Nimesulide
5 Paracetamol + cetrizine + a, S.O. 709 (E)
caffeine 1. Pharmacokinetic incompatibility, as dosing interval for paracetamol is TDS/QID and for cetrizine it is OD/BD.
2. No trial could be found in PUBMED and google scholar.
3. An important safety debate concerning multi- ingredient, multi-symptom relief products for common cold and
flu is that they commonly contain paracetamol (acetaminophen) and that users who may not be aware of this may
accidentally overdose when they take the multi- ingredient product with other medicines also containing
paracetamol.

Eccles, R., Fietze, I. and Rose, U.-B. (2014) Rationale for Treatment of Common Cold and Flu with Multi-
Ingredient Combination Products for Multi-Symptom Relief in Adults. Open Journal of Respiratory Diseases, 4,
73-82.

6 Diclofenac + Tramadol + a, S.O. 710 (E)

Chlorzoxazone 1. Tramadol is an opoid analgesic with abuse liability.
2. The combination will lead to additive sedation.

http://reference.medscape.com/drug-interactionchecker.

7 Dicyclomine +Paracetamol a, S.O. 711 (E)

+Domperidone 1.Pharmacodynamic irrelevant as each ingredient has different therapeutic use and FDC will lead to misuse and
toxicity.
2. Combining can result in dangerous elevation of the body temperature.

Chandler S. Gautam, Lekha Saha. Fixed dose drug combinations (FDCs): rational or irrational: a view point Br
J Clin Pharmacol / 65:5 / 795–796
Eccles, R., Fietze, I. and Rose, U.-B. (2014) Rationale for Treatment of Common Cold and Flu with Multi-
Ingredient Combination Products for Multi-Symptom Relief in Adults. Open Journal of Respiratory Diseases, 4,
73-82.

8 Nimesulide +Paracetamol a, S.O. 712 (E)

dispesible tablets 1. Nimesulide in combination as a dispersible dosage form has potential of misuse in children. There are safety
concerns with nimesuilide FDC with paracetamol.
2. Dose of paracetamol 500mg not approved in FDC with NSAIDs

Chandler S. Gautam, Lekha Saha. Fixed dose drug combinations (FDCs): rational or irrational: a view point Br
J Clin Pharmacol / 65:5 / 795–796
9 Paracetamol + a, S.O. 713 (E)
Phenylephrine + Caffeine Pharmacodynamically irrelevant -
misuse and overuse of one of the ingredient of FDC in case it is not indicated.

Eccles, R., Fietze, I. and Rose, U.-B. (2014) Rationale for Treatment of Common Cold and Flu with Multi-
Ingredient Combination Products for Multi-Symptom Relief in Adults. Open Journal of Respiratory Diseases, 4,
73-82.

10 Diclofenac +Tramadol a, S.O. 714 (E)

+Paracetamol 1.Tramadol is itself a potent opoid analgesic. FDC is not rational as addition of Paracetamol and Diclofenac will
not provide any additional benefit.

11 Diclofenac + paracetamol + a, S.O. 715 (E)

chlorzoxazone + famotidine 1. Pharmacodynamic irrelevant as each ingredient has different dosing shedule/dosing requirement.
2. FDC will lead to misuse and toxicity.
12 Naproxen+Paracetamol This FDC was discussed by previous Committee on 04.06.14- S.O. 716 (E)
There is no scientific justification, the only published literature of this combination has used Paracetamol 4g/day
which is much higher than the proposed dose in the FDC. Hence, the committee did not recommend.
13 Nimesulide + a, S.O. 717 (E)
serratiopeptidase 1. Safety concern with nimesulide
2.No evidence to support that Serratiopeptidase offer any particular advantage over Nimesulide.
3. On the other hand, the patient is exposed to greater risk of gastrointestinal (GI) irritation and serious bleeding
from unsuspected peptic ulceration.

Chandler S. Gautam, Lekha Saha. Fixed dose drug combinations (FDCs): rational or irrational: a view point Br
J Clin Pharmacol / 65:5 / 795–796.

14 Paracetamol +Diclofenac a, S.O. 718 (E)

+Famotidine 1.Pharmacodynamic irrelevant as each ingredient has different therapeutic use and FDC will lead to misuse.
2. Paracetamol dose is high
3. Both diclofenac and paracetamol hepatotoxic
4. An important safety debate concerning multi- ingredient, multi-symptom relief products for common cold and
flu is that they commonly contain paracetamol (acetaminophen) and that users who may not be aware of this may
accidentally overdose when they take the multi- ingredient product with other medicines also containing
paracetamol.

Eccles, R., Fietze, I. and Rose, U.-B. (2014) Rationale for Treatment of Common Cold and Flu with Multi-
Ingredient Combination Products for Multi-Symptom Relief in Adults. Open Journal of Respiratory Diseases, 4,
73-82.
15 Nimesulide + Pitofenone + a, S.O. 719 (E)
Fenpiverinium + benzyl 1.There are no evidences on safety and efficacy of the FDC.
alcohol 2. Safety concern with nimesulide
16 Omeprazole + Paracetamol a, S.O. 720 (E)
+ Diclofenac 1.Pharmacodynamic irrelevant as each ingredient has different therapeutic use and FDC will lead to misuse.
2. Paracetamol dose is high
3. Both diclofenac and paracetamol hepatotoxic
4. An important safety debate concerning multi- ingredient, multi-symptom relief products for common cold and
flu is that they commonly contain paracetamol (acetaminophen) and that users who may not be aware of this may
accidentally overdose when they take the multi- ingredient product with other medicines also containing
paracetamol.

Eccles, R., Fietze, I. and Rose, U.-B. (2014) Rationale for Treatment of Common Cold and Flu with Multi-
Ingredient Combination Products for Multi-Symptom Relief in Adults. Open Journal of Respiratory Diseases, 4,
73-82.

17 Nimesulide + Paracetamol a, S.O. 721 (E)

injection 1.There are safety concerns with nimesuilide
2. Both ingredients are hepatotoxic

18 Tamsulosin + diclofenac a, S.O. 722 (E)

Pharmacodynamically irrelevant - misuse and overuse of one of the ingredient of FDC in case it is not indicated.

19 Paracetamol a, S.O. 723 (E)

+Phenylephirine 1 Dosing schedule is incompatible.
+Chlorpheniramine 2. Ingredients will aggravate the adverse effects of sedation and drowsiness and also will interefere with the
+Dextromethorphan reflexes.
+Caffeine 3.Centrally acting anti-tussive not to be combined with anti-histaminic drug.

20 Diclofenac +Zinc Carnosine a, S.O. 724 (E)

Pharmacodynamically irrelevant - misuse and overuse of one of the ingredient of FDC in case it is not indicated.
21 Diclofenac + paracetamol+ a, S.O. 725 (E)
chlorpheniramine maleate + 1.Pharmacodynamic irrelevant - each ingredient has different therapeutic use and FDC will lead to misuse and
magnesium trisillicate toxicity (hepato and renal).

Eccles, R., Fietze, I. and Rose, U.-B. (2014) Rationale for Treatment of Common Cold and Flu with Multi-
Ingredient Combination Products for Multi-Symptom Relief in Adults. Open Journal of Respiratory Diseases, 4,
73-82.

22 Paracetamol + a, S.O. 726 (E)

pseudoephdrine + cetrizine 1. Pharmacokinetic incompatibility, as dosing interval for paracetamol is TDS/QID and for cetrizine it is OD/BD.
2. No trial could be found in PUBMED and google scholar.
3. An important safety debate concerning multi- ingredient, multi-symptom relief products for common cold and
flu is that they commonly contain paracetamol (acetaminophen) and that users who may not be aware of this may
accidentally overdose when they take the multi- ingredient product with other medicines also containing
paracetamol.

Eccles, R., Fietze, I. and Rose, U.-B. (2014) Rationale for Treatment of Common Cold and Flu with Multi-
Ingredient Combination Products for Multi-Symptom Relief in Adults. Open Journal of Respiratory Diseases, 4,
73-82.

23 Phenylbutazone+Sodium a, S.O. 727 (E)

Salicylate 1.Safety not established and FDC has high risk of toxicity
2. There is no synergism when two drugs acting on the same enzyme are combined. Thus combining two
NSAIDs does not and cannot improve the efficacy of treatment. It only adds to the cost of therapy and more
importantly, to the adverse effects
3. Already prohibited in the country for use in human.

Chandler S. Gautam, Lekha Saha. Fixed dose drug combinations (FDCs): rational or irrational: a view point Br
J Clin Pharmacol / 65:5 / 795–796.

24 Lornoxicam+Paracetamol+T This FDC was discussed by previous Committee on 04.06.14- S.O. 728 (E)
rypsin There is no scientific evidence as well as justification for use of this combination. Hence the committee did not
recommend.
25 Paracetamol +Mefenamic This FDC was discussed by previous Committee on 04.06.14- S.O. 729 (E)
Acid +Ranitidine There is no scientific evidence as well as justification for use of this combination. Hence the committee did not
+Dicyclomine recommend.
26 Nimesulide + Dicyclomine a, S.O. 730 (E)
1.Pharmacodynamic irrelevant as each ingredient has different therapeutic use and FDC will lead to misuse and
toxicity.
2. Combining can result in elevation of the body temperature.

Chandler S. Gautam, Lekha Saha. Fixed dose drug combinations (FDCs): rational or irrational: a view point Br
J Clin Pharmacol / 65:5 / 795–796
Eccles, R., Fietze, I. and Rose, U.-B. (2014) Rationale for Treatment of Common Cold and Flu with Multi-
Ingredient Combination Products for Multi-Symptom Relief in Adults. Open Journal of Respiratory Diseases, 4,
73-82.

27 Heparin +Diclofenac a, S.O. 731 (E)

Pharmacodynamically irrelevant-
Topical use of heparin is irrelevant.

28 Glucosamine +Methyl a, S.O. 732 (E)

Sulfonyl Methane+Vitamin 1. Pharmacodynamic irrelevant as each ingredient has different therapeutic use.
D3 + Manganese + Boron+ 2. therapeutic efficacy of FDC not established and will lead to misuse.
Copper +Zinc
29 Paracetamol +Tapentadol This FDC was discussed by previous Committee on 04.06.14- S.O. 733 (E)
The firm did not turn up for the presentation. The committee noted that the proposal had already been discussed
in NDAC on 17.03.2012 and the committee agreed with the recommendations of the NDAC. Hence the
committee did not recommend.
30 Tranexamic Acid + a, S.O. 734 (E)
Proanthocyanidin Safety and efficacy of Proanthocyanidin in FDC is not established
31 Benzoxonium a, S.O. 735 (E)
Chloride+Lidocaine Pharmacodynamic irrelevant - each ingredient has different therapeutic use and FDC will lead to misuse.
32 Lornoxicam +Paracetamol This FDC was discussed by previous Committee on 04.06.14- S.O. 736 (E)
+Tramadol There is no scientific evidence as well as justification for use of this combination. Hence the committee did not
recommend.
33 Lornoxicam +Paracetamol This FDC was discussed by previous Committee on 04.06.14- S.O. 737 (E)
+Serratiopeptidase There is no scientific evidence as well as justification for use of this combination. Hence the committee did not
recommend.
34 Diclofenac +Paracetamol a, S.O. 738 (E)
+Magnesium trisilicate 1.Pharmacodynamic irrelevant - each ingredient has different therapeutic use and FDC will lead to misuse and
toxicity (hepato and renal).

Eccles, R., Fietze, I. and Rose, U.-B. (2014) Rationale for Treatment of Common Cold and Flu with Multi-
Ingredient Combination Products for Multi-Symptom Relief in Adults. Open Journal of Respiratory Diseases, 4,
73-82.

35 Paracetamol +Domperidone a, S.O. 739 (E)

+Caffeine 1.Pharmacodynamic irrelevant as each ingredient has different therapeutic use and FDC will lead to misuse and
toxicity.

Chandler S. Gautam, Lekha Saha. Fixed dose drug combinations (FDCs): rational or irrational: a view point Br
J Clin Pharmacol / 65:5 / 795–796
Eccles, R., Fietze, I. and Rose, U.-B. (2014) Rationale for Treatment of Common Cold and Flu with Multi-
Ingredient Combination Products for Multi-Symptom Relief in Adults. Open Journal of Respiratory Diseases, 4,
73-82.

36 Ammonium Chloride a, S.O. 740 (E)

+Sodium Citrate 1.Potential of misuse in peadiatric population.
+Chlorpheniramine Maleate 2.Pharmaceutical incompatibility and also the dose of each ingredient is subtherapeutic.
+Menthol
37 Paracetamol a, S.O. 741 (E)
+Prochlorperazine Maleate 1. Pharmacodynamically irrelevant and subtherapeutic dose of Paracetamol.
2. Both ingredients have different indications.

38 Combikit of 3 tablets of a, S.O. 742 (E)

Serratiopeptidase (enteric 1.It will lead to antibiotic resistance.
coated 20000 units) + 2. Documented efficacy of Serratiopeptidase not available.
Diclofenac Potassium & 2 3. May lead to misuse
tablets of Doxycycline 4. Do not offer any particular advantage over the individual drugs. On the other hand, the patient is exposed to
greater risk of gastrointestinal (GI) irritation and serious bleeding from unsuspected peptic ulceration.

Chandler S. Gautam, Lekha Saha. Fixed dose drug combinations (FDCs): rational or irrational: a view point Br
J Clin Pharmacol / 65:5 / 795–796
39 Nimesulide +Paracetamol a, S.O. 743 (E)
suspension 1.Potential misuse in paediatric population
2.Hepatotoxicity
40 Aceclofenac +Paracetamol a, S.O. 744 (E)
+Famotidine 1. Pharmacodynamic irrelevant as each ingredient has different dosing shedule/dosing requirement.
2. FDC will lead to misuse and toxicity.
41 Aceclofenac + Zinc a, S.O. 745 (E)
Carnosine There is no therapeutic benefit of adding zinc carnosine in FDC.

42 Paracetamol + disodium a, S.O. 746 (E)

Hydrogen Citrate + Pharmacodynamically irrelevant
Caffeine 1. Each ingredient has different therapeutic indication.
2. As Urine alkalizer, patients will be unnecessarily exposed to paracetamol and caffeine.

43 Paracetamol + DL a, S.O. 747 (E)

Methionine 1.Pharmacodynamically irrelevant - misuse and overuse of one of the ingredients of FDC in case it is not
indicated.
2.There is no recent peer reviewed scientific data regarding efficacy of Methionine in preventing paracetamol
toxicity in FDC (07.01.2016).

44 Disodium Hydrogen citrate a, S.O. 748 (E)

+Paracetamol 1.Pharmacodynamically irrelevant combination-each ingredient has different therapeutic indication.
2.As Urine alkalizer, patients will be unnecessarily exposed to paracetamol.
45 Paracetamol + Caffeine + a, S.O. 749 (E)
Codeine Phosphate Pharmacodynamically irrelevant.
1.Close Monitoring is required as codeine increases and caffeine decreases sedation.
2.Effect of interaction is not clear, Potential for drug-drug interaction.
3. An important safety debate concerning multi- ingredient, multi-symptom relief products for common cold and
flu is that they commonly contain paracetamol (acetaminophen) and that users who may not be aware of this may
accidentally overdose when they take the multi- ingredient product with other medicines also containing
paracetamol.

http://reference.medscape.com/drug-interactionchecker.
Eccles, R., Fietze, I. and Rose, U.-B. (2014) Rationale for Treatment of Common Cold and Flu with Multi-
Ingredient Combination Products for Multi-Symptom Relief in Adults. Open Journal of Respiratory Diseases, 4,
73-82.

46 Aceclofenac (SR) + a, S.O. 750 (E)

Paracetamol 1.Pharmocokinetic incompatibility-dosing shedule of aceclofenac (SR) and paracetamol are of different duration

47 Diclofenac + Paracetamol a, S.O. 751 (E)

injection 1.Hypersensitivity reaction with lignocaine.
2.Paracetamol dose is subtherapeutic which may increase adverse effects (07.01.2016).

48 Azithromycin+Cefixime Already discussed by previous Committee on 11.06.2014 as under- S.O. 752 (E)
This FDC is not a standard antibiotic combination. This is not the first line combination to be used in any clinical
condition and there is no published scientific data in combining this two drugs. Also in the NDAC meeting held
on 23.08.2013, it was observed that misuse potential of this FDC is very high. Although the FDC may be useful
for certain population of patients of multi-drug resistant typhoid fever or moderate to severe lower respiratory
tract infections, the misuse potential is very high which will cause antimicrobial drug resistance. The firms did
not produce any data on pharmacokinetic and pharmacodynamic interaction as well as safety & efficacy of the
FDC. This FDC is also not approved anywhere in the world. Hence it is not recommended for approval.
49 Amoxicillin +Dicloxacillin
Already discussed by previous Committee on 06.03.2014 as under- S.O. 753 (E)
The committee reviewed following FDC
(i) Amoxicillin 250mg + Dicloxacillin 250mg
(ii)Amoxicillin 125mg + Dicloxacillin 125mg
(iii)Amoxicillin 500mg + Dicloxacillin 500mg
It was noted that Amoxicillin 250mg + Dicloxacillin 250mg was approved by CDSCO in 2006 and the FDC at
(ii) and (iii) are nowbeingrequested by the company. Committee opined that :
(a) Since, 2006 the scenario of antimicrobial resistance pattern has changed significantly, majority of isolates of
Staph. aureus have become resistance to the amoxicillin &cloxacillin including dicloxacillin
(b) Better efficacious antibiotic andare now available and used for staph. aureus infections.
In light of these, the rationality of combination in current scenario is questionable. It is also noted that this
combination is not available anywhere in the world as per information provided by the firm and also the fact that
there is only one study presently by the firm showing better efficacy was published in journal “Pharmazie” Sept.
40(9), 650-1, 1984. However after 30 years, this has lost its relevance in today’s scenario of drug resistance.
Committee therefore doesn’t recommended the new strengths of the FDC and also recommended that the
superiority of such FDC over the individual drug andneed to be proven in current scenario. Accordingly,
50 Amoxicillin 250 Protocol should beby
Already discussed submitted
previouswithin 3 months
Committee and data shall
on 06.03.2014 be generated within next one and half year. Non-
as under- S.O. 754 (E)
mg+Potassium Clavulanate Regarding Amoxycillin 250 mg + clauvulanic Acid 62.5 mg per 5 ml, committee opined that the proposed
Diluted 62.5 mg strength is not recommendable as too many strength will lead to confusion in prescribing for the physician.
Hence the committee did not recommend for the proposed strength
51 Azithromycin + a, S.O. 755 (E)
Levofloxacin 1.Pharmacodynamically irrelevant FDC.
2. Increase risk of emergence of drug resistance due to misuse of FDC .

52 Cefixime +Linezolid a, S.O. 756 (E)

1.Use of antibiotic FDCs can rapidly give rise to resistant strains of organisms, which is a matter of serious
concern to the health care situation in our resource poor country.
2.Lenizolid is a life saving drug to be used for MRSA infection and inappropriate use of lenizolid can lead to
drug resistance.

53 Amoxicillin +Cefixime Already discussed by previous Committee on 06.03.2014 as under- S.O. 757 (E)
+Potassium Clavulanic Acid Committee noted that Cefixime requires 12 hourly dosing. Whereas, Amoxicillin dosing schedule is 6-8 hrs.
When these two drugs are given in combination, it will have a pharmacokinetic mismatch. As claimed by the
firm the dosing of FDC is 12 hourly, which will lead to under dosing of Amoxicillin and may increase possibility
of drug resistance. Further the FDC is not approved anywhere in the world. The committee did not recommend
for the manufacturing and marketing of the FDC
54 Ofloxacin +Nitazoxanide a, S.O. 758 (E)
1. Both ingredients of the FDC have different therapeutic indcations
2.Inappropriate use of nitrazoxanide will lead to emergence of antibiotic resistance against quinalones.
3. Safety concerns in paediatric patients.
55 Cefpodoxime Proxetil Already discussed by previous Committee on 11.06.2014 as under- S.O. 759 (E)
+Levofloxacin Infectious Disease Society of America (IDSA)/ American Thoracic Society (ATS) recommends the combination
of B-lactam + Macrolide for the treatment of community acquired pneumonia and cefpodoxime has been
mentioned as one of the B-lactams. However, the dosage of Azithromycin is 500 mg on day one followed by 250
mg once daily for 4 days while cefpodoxime has to be given 200 mg twice daily for 7 days. Therefore, there is a
mismatch in the dosage schedule of Cefpodoxime + Azithromycin. Although concomitant therapy of two drugs
may be required in some patients of CAP however there is no dose compatibility. It was observed that misuse
potential of this FDC is very high which will cause antimicrobial drug resistance. Hence, the FDC for CAP is not
recommended for approval.

In gonorrhea, the recommended dose is either azithromycin 1g as single dose or cefpodoxime 400 mg single
dose. Therefore the proposed FDC is not recommended for approval.

56 Combikit of Azithromycin a, S.O. 760 (E)

dihydrate, secnidazole and 1. Pharmacodynamically irrelevant due to different therapeutic indications of ingredients. FDC may Increase risk
fluconazole of emergence of drug resistance.
2. Patient may require only one ingredient
3. Azithromycin and fluconazole both increase QTc interval, Potential cardiac toxicity.
http://reference.medscape.com/drug-interactionchecker.

4.The Committee reexamined the combikit of this formulation and it was opined that all the three drugs are not
used for same duration in treatment of PID, Vaginal infection.The use of azithromycin is not as per the CDC
guidelines (07.01.2016).

57 Levofloxacin +Ornidazole a, S.O. 761 (E)

+Alpha Tocopherol Acetate 1. Patient may need only one ingredient and the use of FDC may lead to misuse.
2. Increased risk of emergence of drug resistance due to misuse of FDC .

58 Nimorazole+Ofloxacin a, S.O. 762 (E)

1. Patient may need only one ingredient and the use of FDC may lead to misuse.
2. Increased risk of emergence of drug resistance due to misuse of FDC .

59 Azithromycin + ofloxacin a, S.O. 763 (E)

1.Pharmacodynamically irrelevant FDC.
2. Increased risk of emergence of drug resistance due to misuse of FDC .
60 amoxycillin + tinidazole Already discussed by previous Committee on 06.03.2014 as under- S.O. 764 (E)
The committee noted that the pharmacokinetics of Amoxicillin require dosing frequency 6-8 hourly. In
contradiction Tinidazole dosing is twice a day. Further the proposed indications are not as per the clinical
indication of these two individual drugs such as Amoebiasis. Tinidazole is good enough for the treatment of
amoebiasis and Amoxicillin does not have any role and therefore the FDC does not have any rationale. Even for
H. pylori infection the proposed FDC is not rationale. The proposed FDC is also not approved anywhere in the
world. Hence the committee didn’t recommend the FDC for manufacturing and marketing.
61 Doxycycline a, S.O. 765 (E)
+Serratiopeptidase Pharmacodynamically irrelevant-
1. Increased risk of emergence of drug resistance.
2. Patient may need only one ingredient and use of FDC may lead to misuse.

62 Cefixime +levofloxacin a, S.O. 766 (E)

1.Pharmacodynamically irrelevant FDC.
2. Increased risk of emergence of drug resistance due to misuse of FDC .

63 Ofloxacin +Metronidazole a, S.O. 767 (E)

+Zinc Acetate 1. Both ingredients of the FDC have different therapeutic indcations
2.Inappropriate use of metronidazole will lead to emergence of antibiotic resistance against quinalones.
3. Safety concerns in paediatric patients.

64 Diphenoxylate +Atropine a, S.O. 768 (E)

+Furazolidone Pharmacodynamically irrelevant-
1. Patient may need only one ingredient which may lead to misuse and adverse effect.
2. Use of two antispasmodic can develop more risk of adverse effect.
3. Use of antibacterial in FDC is irrelevant.

65 Combikit of Fluconazole a, S.O. 769 (E)

Tablet, Azithromycin Tablet Pharmacodynamically irrelevant-
and Ornidazole Tablets 1.Each ingredients of FDC has different therapeutic indication and is at variance from the concept and purpose of
FDC.
2. Combining antibiotic , antifungal, in the present FDC is liable to be misuse and emergence of resistance and
adverse effects.
3. NO study is found supporting the combined use of an antibacterial with an antifungal ingredient.
66 Ciprofloxacin Already discussed by previous Committee on 11.06.2014 as under- S.O. 770 (E)
+Phenazopyridine Ciprofloxacin is an antibiotic and phenazopyridine is urinary analgesic for symptomatic relief. Normally
ciprofloxacin is used for 5 to 7 days but phenazopyridine is not recommended for more than 2 days due to its
serious side effects. Hence, this combination is not rational and the committee did not recommend for approval.
67 Amoxycillin +Dicloxacillin Already discussed by previous Committee on 06.03.2014 as under- S.O. 771 (E)
+Serratiopeptidase Committee opined that combination of serratiopeptidase with antibiotics has no rationale. Hence Committee
didn’t recommend for manufacturing and marketing of the proposed FDC (REJECTED)
68 Azithromycin Already discussed by previous Committee on 11.06.2014 as under- S.O. 772 (E)
+Cefpodoxime Infectious Disease Society of America (IDSA)/ American Thoracic Society (ATS) recommends the combination
of B-lactam + Macrolide for the treatment of community acquired pneumonia and cefpodoxime has been
mentioned as one of the B-lactams. However, the dosage of Azithromycin is 500 mg on day one followed by 250
mg once daily for 4 days while cefpodoxime has to be given 200 mg twice daily for 7 days. Therefore, there is a
mismatch in the dosage schedule of Cefpodoxime + Azithromycin. Although concomitant therapy of two drugs
may be required in some patients of CAP however there is no dose compatibility. It was observed that misuse
potential of this FDC is very high which will cause antimicrobial drug resistance. Hence, the FDC for CAP is not
recommended for approval.

In gonorrhea, the recommended dose is either azithromycin 1g as single dose or cefpodoxime 400 mg single
dose. Therefore the proposed FDC is not recommended for approval.

69 Lignocaine+Clotrimazole+O a, S.O. 773 (E)

floxacin+Beclomethasone Pharmacodynamically irrelevant-
1.Each ingredients of FDC has different therapeutic indication and is at variance from the concept and purpose of
FDC.
2. Combining antibiotic , antifungal, steroid in the present FDC is liable to be misuse and emergence of
resistance and adverse effects.
3.Use of steroid in case of fungal infection might actually worsen the treatment as it encourages fungal growth.
NO study is found supporting the combined use of an antibacterial with an antifungal ingredient.
4.Lignocaine use in discharging ear is not required (07.01.2016).
70 Cafuroxime + Linezolid a, S.O. 774 (E)
1.Use of antibiotic FDCs can rapidly give rise to resistant strains of organisms, which is a matter of serious
concern to the health care situation in our resource poor country.
2.Lenizolid is a life saving drug to be used for MRSA infection and inappropriate use of lenizolid can lead to
drug resistance.

71 Ofloxacin +Ornidazole a, S.O. 775 (E)

+Zinc bisglycinate 1. Both ingredients of the FDC have different therapeutic indcations
2.Inappropriate use of ornidazole will lead to emergence of antibiotic resistance against quinalones.
3. Safety concerns in paediatric patients.
72 Metronidazole +Norfloxacin a, S.O. 776 (E)
1.FDCs of quinolones and nitroimidazoles (e.g. norfloxacin + metronidazole, ciprofloxacin + tinidazole,
ofloxacin + ornidazole) have not been recommended in children.
2.This FDC can rapidly give rise to resistant strains of organisms, which is a matter of serious concern to the
health care situation in our resource poor country.

Kasarla Raju1, A. Elumalai2, Eddla Srid. IRRATIONAL DRUG COMBINATIONS. Vol 3|Issue 2| 2013 | 52-56

73 Amoxicillin+Bromhexine a, S.O. 777 (E)

Pharmacodynamically irrelevant-
1. Combining amoxycillin (antibiotic) with other ingredient which has different indication is irrational and will
lead to emergence of resistance.
2. There is no justification in combining mucolytic ingredient with antibacterial, as thick secretions in respiratory
tract are always not due to respiratory infections. Also the antibacterial therapy always does not require an
associated dose of mucolytic ingredient.

Kasarla Raju, A. Elumalai, Eddla Srid. IRRATIONAL DRUG COMBINATIONS. Vol 3|Issue 2| 2013 | 52-56.

74 Ciprofloxacin +Fluticasone a, S.O. 778 (E)

+Clotrimazole +Neomycin Pharmacodynamically irrelevant-
1.Each ingredients of FDC has different therapeutic indication and is at variance from the concept and purpose of
FDC.
2. Combining two antibiotics , antifungal, steroid in the present FDC is liable to be misused and emergence of
resistance and adverse effects.
3.NO study is found supporting the combined use of ingredients in this FDC.
75 Metronidazole a, S.O. 779 (E)
+Tetracycline Pharmacodynamically irrelevant-
May lead to misuse and antibiotic resistance
76 Cephalexin + Neomycin a, S.O. 780 (E)
+Prednisolone Pharmacodynamically irrelevant-
1.May lead to misuse and neomycin is a potent nephrotoxic. It is no longer indicated by parentral route.
77 Azithromycin + Ambroxol a, S.O. 781 (E)
Pharmacodynamically irrelevant-
1. Combining Azithromycin (antibiotic) with other ingredient which has different indication is irrational and will
lead to emergence of resistance.
2. There is no justification in combining mucolytic ingredient with antibacterial, as thick secretions in respiratory
tract are always not due to respiratory infections. Also the antibacterial therapy always does not require an
associated dose of mucolytic ingredient.

Kasarla Raju, A. Elumalai, Eddla Srid. IRRATIONAL DRUG COMBINATIONS. Vol 3|Issue 2| 2013 | 52-56.

78 cilnidipine + metroprolol a, S.O. 782 (E)

succinate + metroprolol Pharmacodynamically irrelevant,there is no scientific justification for two derivatives of metoprolol.
tartrate Same compound in differerent salt form don’t make any pharmacodynamic (Synergistic/additive) hence dose of
metoprolol selected in the combination is questionable
79 L-Arginine +Sildenafil a, S.O. 783 (E)
Pharmacodynamically irrelevant as there is lack of synergism or additive effect and also the dose selection is
questionable
80 atorvastatin + vitamin D3 + a, S.O. 784 (E)
folic acid + vitamin B12 + Pharmacodynamically irrelevant-
pyridoxine 1.Atovastatin has definite indication and combining it with vitamins has no additional benefit.
2. Misuse of FDC as vitamin supplement will cause serious adverse effects of atorvastatin.

81 Metformin+Atorvastatin This FDC was discussed earlier by previous Committee on 27.08.14 as under- S.O. 785 (E)
The committee opined that there is no advantage of proposed fixed dose combination of atorvastatin and
metformin.
The dose of atorvastatin depends on the clinical condition and risk factors and accordingly, the dose may range
from 10 mg to 80 mg. So the FDC will not be useful in titration of doses. Hence the committee did not
recommended the proposed strength.

82 Clindamycin+Telmisartan a, S.O. 786 (E)

Pharmacodynamically irrelevant-
1. Use of antibiotic with angiotensin receptor blocker is not rational
83 Olmesartan+Hydrochlorothi a, S.O. 787 (E)
azide +Chlorthalidone 1. Both diuretics present in the FDC have same mechanism of action.
2. Dose trituration will be difficult in FDC.
3. Chlorthalidone will increase the level or effect of hydrochlorothiazide by acidic (anionic) drug competition for
renal tubular clearance.
84 L-5-Methylterahydrofolate a, S.O. 788 (E)
calcium + Escitalopram Pharmacodynamically irrelevant-
1. No supporting published literature available on the combination.
2. Both ingredients have different indications.

85 pholcodine +Promethazine a, S.O. 789 (E)

1 Dosing schedule is incompatible.
2. Ingredients will aggravate the adverse effects of sedation and drowsiness and also will interefere with the
reflexes.
3.Centrally acting anti-tussive not to be combined with anti-histaminic drug.

86 Paracetamol +Promethazine a, S.O. 790 (E)

1. Pharmacodynamically irrelevant.
2. Both ingredients have different indications.

87 Betahistine +Ginkgo Biloba a, S.O. 791 (E)

Extract+Vinpocetine+Pirace Pharmacodynamic irrelevant - each ingredient has different therapeutic use and FDC will lead to misuse.
tam
88 Cetirizine Dihydrochloride a, S.O. 792 (E)
+Diethyl Carbamazine 1. Patient may need only one ingredient and use of FDC may lead to misuse.
89 Doxylamine +Pyridoxine a, S.O. 793 (E)
+Mefenamic Pharmacodynamically irrelevant-
Acid+Paracetamol 1. No published literature supporting the FDC.
2. Users who may not be aware of this mefanamic acid content and may accidentally overdose when they take the
multi- ingredient product with other medicines also containing paracetamol.
3. If misused for morning sickness, it is teratogenic.

Eccles, R., Fietze, I. and Rose, U.-B. (2014) Rationale for Treatment of Common Cold and Flu with Multi-
Ingredient Combination Products for Multi-Symptom Relief in Adults. Open Journal of Respiratory Diseases, 4,
73-82.

90 Drotaverine + Clidinium This FDC was earlier discussed by previous Committee on 05.09.2014 as under- S.O. 794 (E)
+ Chlordiazepoxide There is no scientific evidence as well as justification for use of this combination. Hence the committee did not
recommend.
91 Imipramine + Diazepam a, S.O. 795 (E)
Pharmacodynamically irrelevant-
1. Diazepam and imipramine both increase sedation.
2. Potential for interaction.

http://reference.medscape.com/drug-interactionchecker.
92 Flupentixol +Escitalopram a, S.O. 796 (E)
Pharmacodynamically irrelevant-
1. No supporting published literature for this FDC.
2. The combination will aggravate the adverse effects.
93 Paracetamol + a, S.O. 797 (E)
Prochloperazine 1. Pharmacodynamically irrelevant.
2. Both ingredients have different indications.

94 Gabapentin +Mecobalamin a, S.O. 798 (E)

+Pyridoxine +Thiamine Pharmacodynamically irrelevant-
gabapentin decreases levels of cyanocobalamin by inhibition of GI absorption.

http://reference.medscape.com/drug-interactionchecker.
95 Imipramine a, S.O. 799 (E)
+Chlordiazepoxide Pharmacodynamically irrelevant-
+Trifluoperazine
+Trihexyphenidyl 1.Trifluoperazine and imipramine both increase QTc interval.
2. High likelihood serious or life-threatening interaction.
3.Trihexyphenidyl and imipramine both decrease cholinergic effects/transmission.
4.chlordiazepoxide and trifluoperazine both increase sedation.
5.Trihexyphenidyl decreases levels of trifluoperazine by pharmacodynamic antagonism.

http://reference.medscape.com/drug-interactionchecker.

96 Chlorpromazine a, Pharmacodynamically irrelevant- S.O. 800 (E)

+Trihexyphenidyl 1.In current scenerio chlorpromazine is not a drug of choice for the treatment of depression.
2. dose adjustment of Trihexyphenidyl to counteract the adverse effect of chlorpromazine is not possible in FDC
formulation
3.There is a risk of potential abuse
97 Ursodeoxycholic Acid + a, S.O. 801 (E)
Silymarine Pharmacodynamically irrelevant-
1. UDCA is used for PBC and silymarin is a hepatoprotective.
2. Silymarin does not provide any benefit to patients with Primary Biliary Cirrhosis.

`. Metformin This FDC was discussed earlier by previous Committee on 27.08.14 as under- S.O. 802 (E)
1000/1000/500/500mg The usual dose of pioglitazone is 15 mg. Firm(s) presented two studies one Indian study of pioglitazone 7.5 mg
+Pioglitazone with other Oral hypoglycemic drugs and Japanese study of comparison of 7.5 mg of pioglitazone with15 mg of
7.5/7.5/7.5/7.5mg + pioglitazone. The scientific evidence from both the studies is not enough to justify 7.5 mg dose of pioglitazone in
Glimepiride 1/2/1/2mg FDC. Committee also opined that there is no sufficient pharmacokinetic and pharmacodynamic data. Further the
committee also noted that the proposed FDC in proposed strengths has already been deliberated by NDAC on
22.08.2012 and NDAC did not recommend the FDC. This committee also endorsed the comments of the NDAC
and did not recommend. Moreover the firm(s) also did not present any additional data to counter the comments
of NDAC made on 22.08.2012.
However, the proposal for Pioglitazone HCl 15mg +Metformin HCl 500mg(SR) +Glimepiride 1mg/2mg Tablets
is already approved by DCG(I) on 16.08.2005 and hence this strength was not deliberated.

99 Gliclazide 80 mg + a, S.O. 803 (E)

metformin 325 mg Sub-therapeutic dose of metformin.

100 Voglibose+ Metformin + a, S.O. 804 (E)

Chromium Picolinate Pharmacodynamically irrelevant-
1.No published literature supporting the superior efficacy of combination of these drugs.
2. Therapeutic use of chromium is doubtfull.
101 Pioglitazone a, S.O. 805 (E)
7.5/7.5mg+Metformin 1. Subtherapeutic dose of Pioglitazone.
500/1000mg 2. Safety issue with Pioglitazone especially as FDC.
102 Glimepiride a, S.O. 806 (E)
1mg/2mg/3mg+Pioglitazone 1. There is no published literature supporting this FDC.
15mg/15mg/15mg+Metform 2. The Pioglitazone has safety concerns.
in
1000mg/1000mg/1000mg
103 glimepiride 1mg/2mg+ a, S.O. 807 (E)
pioglitazone 15mg/15mg + 1. There is no published literature supporting this FDC.
metformin 850mg/850mg 2. The Pioglitazone has safety concerns.
104 Metformin This FDC was discussed earlier by previous Committee on 27.08.14 as under- S.O. 808 (E)
850mg+Pioglitazone 7.5 The usual dose of pioglitazone is 15 mg. Firm(s) presented two studies one Indian study of pioglitazone 7.5 mg
mg+Glimepiride 2mg with other Oral hypoglycemic drugs and Japanese study of comparison of 7.5 mg of pioglitazone with15 mg of
pioglitazone. The scientific evidence from both the studies is not enough to justify 7.5 mg dose of pioglitazone in
FDC. Committee also opined that there is no sufficient pharmacokinetic and pharmacodynamic data. Further the
committee also noted that the proposed FDC in proposed strengths has already been deliberated by NDAC on
22.08.2012 and NDAC did not recommend the FDC. This committee also endorsed the comments of the NDAC
and did not recommend. Moreover the firm(s) also did not present any additional data to counter the comments
of NDAC made on 22.08.2012.
However, the proposal for Pioglitazone HCl 15mg +Metformin HCl 500mg(SR) +Glimepiride 1mg/2mg Tablets
is already approved by DCG(I) on 16.08.2005 and hence this strength was not deliberated.

105 Metformin This FDC was discussed earlier by previous Committee on 27.08.14 as under- S.O. 809 (E)
850mg+Pioglitazone 7.5 The usual dose of pioglitazone is 15 mg. Firm(s) presented two studies one Indian study of pioglitazone 7.5 mg
mg+Glimepiride 1mg with other Oral hypoglycemic drugs and Japanese study of comparison of 7.5 mg of pioglitazone with15 mg of
pioglitazone. The scientific evidence from both the studies is not enough to justify 7.5 mg dose of pioglitazone in
FDC. Committee also opined that there is no sufficient pharmacokinetic and pharmacodynamic data. Further the
committee also noted that the proposed FDC in proposed strengths has already been deliberated by NDAC on
22.08.2012 and NDAC did not recommend the FDC. This committee also endorsed the comments of the NDAC
and did not recommend. Moreover the firm(s) also did not present any additional data to counter the comments
of NDAC made on 22.08.2012.
However, the proposal for Pioglitazone HCl 15mg +Metformin HCl 500mg(SR) +Glimepiride 1mg/2mg Tablets
is already approved by DCG(I) on 16.08.2005 and hence this strength was not deliberated.

106 Metformin a, S.O. 810 (E)

500mg/500mg+Gliclazide Pharmacodynamically irrelevant-
SR 1. Subtherapeutic dose of Pioglitazone.
30mg/60mg+Pioglitazone 2. Pioglitazone has safety concerns.
7.5mg/7.5mg
107 Voglibose+Pioglitazone+Mea, S.O. 811 (E)
tformin Pharmacodynamically irrelevant-
1. Subtherapeutic dose of pioglitazone.
2. Safety concerns of pioglitazone.
3. No published literature supporting this FDC.
108 Metformin +bromocriptine a, S.O. 812 (E)
Pharmacodynamically irrelevant-
1. No published literature supporting the use of combination.
2. Both ingredients have different indication.
109 Metformin +Glimepiride a, S.O. 813 (E)
+Methylcobalamin Pharmacodynamically irrelevant-
1. No published literature supporting the superior efficacy of combination of three drugs.
2. Use of methylcobalamine as prophylaxis in FDC is not documented.
110 Pioglitazone 30 a, S.O. 814 (E)
mg+Metformin 500mg Safety issue with Pioglitazone especially as FDC.
111 Glimepiride +Pioglitazone a, S.O. 815 (E)
+Metformin 1. There is no published literature supporting this FDC.
2. The Pioglitazone has safety concerns.
112 Glipizide 2.5mg+Metformin This FDC was discussed earlier by previous Committee on 27.08.14 as under- S.O. 816 (E)
400mg The firm could not present any scientific data with respect to the proposed strength of FDC. The committee
opined that the proposed strength is not going to add any benefit to the patient over the already approved
strengths of the FDC. Hence the committee did not recommend.
113 Pioglitazone a, S.O. 817 (E)
15mg+Metformin 850 mg Safety issue with Pioglitazone especially as FDC.
114 Metformin ER+Gliclazide This FDC was discussed earlier by previous Committee on 27.08.14 as under- S.O. 818 (E)
MR+Voglibose The firm could not present any scientific data with respect to this FDC. The dosing of voglibose is incompatible
with the dosing schedule of metformin ER and gliclazide SR. Hence the committee did not recommend.

115 Chromium a, S.O. 819 (E)

Polynicotinate+Metformin Pharmacodynamically irrelevant-
Hydrochloride 1.No published literature supporting the superior efficacy of combination of these drugs.
2.There is a controversy regarding the use of chromium.
116 Metformin Hydrochlopride a, S.O. 820 (E)
+Gliclazide +Piogllitazone Pharmacodynamically irrelevant-
+Chromium Polynicotinate 1. There is no published literature supporting this FDC.
2. The Pioglitazone has safety concerns.
3. It is at variance from the concept and purpose of FDC.
117 Metformin +Gliclazide a, S.O. 821 (E)
+Chromium Polynicotinate Pharmacodynamically irrelevant-
1. No published literature is available supporting the superior efficacy of combination of three drugs
2. there is a controversy regarding the use of chromium.

118 Glibenclamide + Metformin a, S.O. 822 (E)

(SR)+ Pioglitazone 1. There is no published literature supporting this FDC.
2. The Pioglitazone has safety concerns.
119 Metformin (sustainded a, S.O. 823 (E)
release) Pharmacodynamically irrelevant-
500mg+Pioglitazone 15 1. There is no published literature supporting this FDC.
mg+Glimepride 3mg 2. The Pioglitazone has safety concerns.
3. It is at variance from the concept and purpose of FDC.
120 Metformin (SR) a, S.O. 824 (E)
500mg+Pioglitazone 5mg Pharmacodynamically irrelevant-
1. Subtherapeutic dose of Pioglitazone.
2. Pioglitazone has safety concerns.
121 Chloramphenicol a, S.O. 825 (E)
+Beclomethasone Pharmacodynamically irrelevant-
+Clomitrimazole 1.Each ingredients of FDC has different therapeutic indication and is at variance from the concept and purpose of
+Lignocaine FDC.
2. Combining antibiotic , antifungal, steroid in the present FDC is liable to be misuse and emergence of
resistance and adverse effects.
3.Use of steroid in case of fungal infection might actually worsen the treatment as it encourages fungal growth.
NO study is found supporting the combined use of an antibacterial with an antifungal ingredient.
4.Lignocaine use in discharging ear is not required (07.01.2016).
122 Clotrimazole + Ofloxaxin + a, S.O. 826 (E)
Lignocaine + glycerine and Pharmacodynamically irrelevant-
propylene glycol 1.Each ingredients of FDC has different therapeutic indication and is at variance from the concept and purpose of
FDC.
2. Combining antibiotic , antifungal,in the present FDC is liable to be misuse and emergence of resistance and
adverse effects.
3.NO study is found supporting the combined use of an antibacterial with an antifungal ingredient.
4.Lignocaine use in discharging ear is not required (07.01.2016).
123 Chloramphennicol+Lignocai a, S.O. 827 (E)
n+Betamethasone+Clotrima Pharmacodynamically irrelevant-
zole+Ofloxacin+Antipyrine 1.Each ingredients of FDC has different therapeutic indication and is at variance from the concept and purpose of
FDC.
2. Combining antibiotic , antifungal, steroid in the present FDC is liable to be misuse and emergence of
resistance and adverse effects.
3.Use of steroid in case of fungal infection might actually worsen the treatment as it encourages fungal growth.
NO study is found supporting the combined use of an antibacterial with an antifungal ingredient.
4.Lignocaine use in discharging ear is not required (07.01.2016).
124 Ofloxacin +Clotrimazole a, S.O. 828 (E)
+Betamethasone Pharmacodynamically irrelevant-
+Lignocaine 1.Each ingredients of FDC has different therapeutic indication and is at variance from the concept and purpose of
FDC.
2. Combining antibiotic , antifungal, steroid in the present FDC is liable to be misuse and emergence of
resistance and adverse effects.
3.Use of steroid in case of fungal infection might actually worsen the treatment as it encourages fungal growth.
NO study is found supporting the combined use of an antibacterial with an antifungal ingredient.
4.Lignocaine use in discharging ear is not required (07.01.2016).
125 Gentamicin Sulphate a, S.O. 829 (E)
+Clotrimazole Pharmacodynamically irrelevant-
+Betamethasone 1.Each ingredients of FDC has different therapeutic indication and is at variance from the concept and purpose of
+Lignocaine FDC.
2. Combining antibiotic , antifungal, steroid in the present FDC is liable to be misuse and emergence of
resistance and adverse effects.
3.Use of steroid in case of fungal infection might actually worsen the treatment as it encourages fungal growth.
NO study is found supporting the combined use of an antibacterial with an antifungal ingredient.
4.Lignocaine use in discharging ear is not required (07.01.2016).
126 Clotrimazole a, S.O. 830 (E)
+Beclomethasone Pharmacodynamically irrelevant-
+Ofloxacin +Lignocaine 1.Each ingredients of FDC has different therapeutic indication and is at variance from the concept and purpose of
FDC.
2. Combining antibiotic , antifungal, steroid in the present FDC is liable to be misuse and emergence of
resistance and adverse effects.
3.Use of steroid in case of fungal infection might actually worsen the treatment as it encourages fungal growth.
NO study is found supporting the combined use of an antibacterial with an antifungal ingredient.
4.Lignocaine use in discharging ear is not required (07.01.2016).
127 Becloemthasone a, S.O. 831 (E)
+Clotrimazole+Chloramphe Pharmacodynamically irrelevant-
nicol+Gentamycin 1.Each ingredients of FDC has different therapeutic indication and is at variance from the concept and purpose of
+Lignocaine Ear drops FDC.
2. Combining antibiotic , antifungal, steroid in the present FDC is liable to be misuse and emergence of
resistance and adverse effects.
3.Use of steroid in case of fungal infection might actually worsen the treatment as it encourages fungal growth.
NO study is found supporting the combined use of an antibacterial with an antifungal ingredient.
4.Lignocaine use in discharging ear is not required (07.01.2016).
128 Flunarizine + a, S.O. 832 (E)
Paracetamole+ Pharmacodynamically irrelevant-
Domperidone 1. Indication for each drug is different.
2. There is no common condition in which all three drugs are useful.
3. In case of migraine, flunarizine is used for prophylaxis, whereas paracetamol and domperidone are used for
acute attack treatment.
129 Rabeprazole +Zinc a, S.O. 833 (E)
carnosine Pharmacodynamically irrelevant-
1.No published literature supporting the FDC.
2.Potential for adverse effects.
130 magaldrate + famotidine + a, S.O. 834 (E)
simethicone Pharmacodynamically irrelevant-
1. Subtherapeutic dose of Famotidine.
2. No evidence of efficacy exists supporting the use of triple drug combination.
131 cyproheptadine + thiamine a, S.O. 835 (E)
1. Pharmacodynamically irrelevant.
2..No publish literature is available to support the FDC.

132 Magaldrate +Ranitidine a, S.O. 836 (E)

+Pancreatin +Domperidone Pharmacodynamically irrelevant-
1. There is no use of combining an antiemetic ingredient (domperidone) with drugs for peptic ulcer as vomiting
may not always be associated with it.
2. Pharmacokinetic incompatibility.
133 Ranitidine +Magaldrate a, S.O. 837 (E)
+simethicone Pharmacodynamically irrelevant-
No published literature supporting the FDC.
134 magaldrate + papain+ fungul a, S.O. 838 (E)
diastase + simethicone Pharmacodynamically irrelevant-
1. Papain and fungal diastase are digestive enzymes. Simethicone an anti foaming ingredient is used to reduce
bloating sensation due to excessive gas production.
2. No published literature supporting the mechanism of action or efficacy for the combination is available.
3.Use of Magaldrate is not justified (08.01.2016).
135 Rabeprazole + zinc + a, S.O. 839 (E)
domperidone Pharmacodynamically irrelevant-
1.No published literature supporting the FDC.
2.Potential for adverse effects.
136 Famotidine + oxytacaine + a, S.O. 840 (E)
Magaldrate Pharmacodynamically irrelevant-
No published literature supporting the FDC.
137 Ranitidine+Domperidone+S a, S.O. 841 (E)
emithicone Pharmacodynamically irrelevant-
No published literature supporting the FDC.
138 Alginic Acid+Sodium This FDC was earlier discussed by previous Committee on 05.09.2014 as under- S.O. 842 (E)
Bicarbonate+Dried The committee opined that internationally there is no authentic reference for inclusion of sodium bicarbonate in a
Aluminium combined antacid formulation. Sodium bicarbonate is a systemic alkalinizer and not a locally acting antacid.
Hydroxide+Magnesium There is risk of systemic adverse effects on chronic use of such products. Hence the committee did not
Hydroxide recommend such FDC.
139 Clidinium +Paracetamol a, S.O. 843 (E)
+Dicyclomine +Activated Pharmacodynamic irrelevant-
Dimethicone 1.Each ingredients have different therapeutic use and FDC will lead to misuse.
2.Pain of petic ulcer is not due to spasm and hence there is no rationale for combining with dicyclomine
140 Furazolidone a, S.O. 844 (E)
+Metronidazole Pharmacodynamically irrelevant-
+Loperamide 1.antimotility drug will cause toxic megacolon in infective diarrhoea.
2. Loperamide is contra-indicated in infective diarrhea and in patients with bacterial enterocolitis caused by
invasive organisms including Salmonella, Shigella, and Campylobacter as it reduces the clearance of pathogens.
Hence there is no rationale for combining with antibiotic in an FDC.
3. In bacterial diarrhoea only anti-bacterial drug is effective and antiamoebic drug is useless. Similarly, in
intestinal amoebiasis only antiamoebic drug is effective while antibacterial drug is useless.
4.Amoebiasis and bacterial diarrhoea rarely coexist.
5. Only one drug of the combination would be effective and the other one would be useless.
141 Rabeprazole +Diclofenac a, S.O. 845 (E)
+Paracetamol 1.Pharmacokinetic/Pharmacodynamic incompatibility.
2.Subtherapeutic dose of rabeprazole.
3.No published literature support combination of rabeprazole with diclofenac and paracetamol.

142 Ranitidine +Magaldrate a, S.O. 846 (E)

Pharmacodynamically irrelevant-
No published literature supporting the FDC.
143 Norfloxacin+ Metronidazole a, S.O. 847 (E)
+ zinc Acetate 1.FDCs of quinolones and nitroimidazoles (e.g. norfloxacin + metronidazole, ciprofloxacin + tinidazole,
ofloxacin + ornidazole) have not been recommended in children.
2.This FDC can rapidly give rise to resistant strains of organisms, which is a matter of serious concern to the
health care situation in our resource poor country.

Kasarla Raju, A. Elumalai, Eddla Srid. IRRATIONAL DRUG COMBINATIONS. 2013;3(2):52-56.

144 Zinc Carnosine+Oxetacaine a, S.O. 848 (E)

Pharmacodynamically irrelevant-
1. No published literature supporting this FDC.
145 Oxetacaine +Magaldrate a, S.O. 849 (E)
+Famotidine Pharmacodynamically irrelevant-
No published literature supporting the FDC.
146 Pantoprazole (as Enteric a, S.O. 850 (E)
Coated Tablet)+Zinc Pharmacodynamically irrelevant-
Carnosine (as Film Coated No published literature supporting the FDC.
Tablets)
147 Zinc a, S.O. 851 (E)
Carnosine+MagnesiumHydr Pharmacodynamically irrelevant-
oxide +Dried Aluminium 1. No published literature supporting this FDC.
Hydroxide +Simethicone
148 Zinc Carnosine+Sucralfate a, S.O. 852 (E)
Pharmacodynamically irrelevant-
1. No published literature supporting this FDC.
149 Mebeverine Hydrochloride a, S.O. 853 (E)
& Inner HPMC capsule Pharmacodynamically irrelevant-
(Streptococcus Faecalis 1. No published literature supporting the use of combination.
+Clostridium butyricum 2. Mebeverine is used for relieving spasm in treatment of irritable bowel syndrome (IBS) and the associated
+Bacillus abdominal cramping.
mesentricus+Lactic Acid 3. Therapeutic indication of Mebeverine and Probiotic are different.
Bacillus)
150 Clindamycin +Clotrimazole This FDC was discussed by previous Committee on 22.08.2014 as under- S.O. 854 (E)
+Lactic Acid Bacillus Committee opined that the FDC is not rational. As firm did not present any evidence with regards to its
superiority and further drug resistant lactic acid bacillus spores in this combination may spread community drug
resistance. Hence, the committee did not recommend.
151 Sildenafil +Estradiol a, S.O. 855 (E)
Valerate Pharmacodynamically irrelevant-
1. Both ingredients have different indications.
2. No clinical studies are found supporting this combination.
152 Clomifene Citrate a, S.O. 856 (E)
+Ubidecarenone +Zinc 1.No published literature supporting this combination of a ovulation inducing ingredient( clomiphene) with
+Folic Acid multivitamins and antioxidants.
+Methylcobalamin 2.Clomifene is used for only five days . Others drugs like folic acid ,Lycopene etc.need to be used for at least two
+Pyridoxine +Lycopene month prior to clomifene therapy (07.01.2016)
+Selenium+Levocarnitine
Tartrate+L-Arginine
153 Thyroxine + Pyridoxine + a, S.O. 857 (E)
Folic Acid No clinical studies found supporting the use of this combination
154 Gentamycin+Dexamethason a, S.O. 858 (E)
e+Chloramphenicol+Tobra Pharmacodynamically irrelevant-
mycin+Ofloxacin 1.Each ingredients of FDC has different therapeutic indication and is at variance from the concept and purpose of
FDC.
2. Combining antibiotic , antifungal, steroid in the present FDC is liable to be misuse and emergence of
resistance and adverse effects.
3.Use of steroid in case of fungal infection might actually worsen the treatment as it encourages fungal growth.
NO study is found supporting the combined use of an antibacterial with an antifungal ingredient.
155 Dextromethorphan + a, S.O. 859 (E)
Levocetirizine 1 Dosing schedule is incompatible.
+Phenylephrine +Zinc 2. Ingredients will aggravate the adverse effects of sedation and drowsiness and also will interefere with the
reflexes.
3.Centrally acting anti-tussive not to be combined with anti-histaminic drug.
156 Nimesulide +Loratadine a, S.O. 860 (E)
+Phenylephrine +Ambroxol Pharmacodynamic irrelevant-
1.Each ingredient has different therapeutic use and FDC will lead to misuse and toxicity.
2. Pharmacokinetic mismatch.

Chandler S. Gautam, Lekha Saha. Fixed dose drug combinations (FDCs): rational or irrational: a view point Br
J Clin Pharmacol / 65:5 / 795–796
Eccles, R., Fietze, I. and Rose, U.-B. (2014) Rationale for Treatment of Common Cold and Flu with Multi-
Ingredient Combination Products for Multi-Symptom Relief in Adults. Open Journal of Respiratory Diseases, 4,
73-82.

157 Bromhexine a, S.O. 861 (E)

+Phenylephrine Pharmacodynamically irrelevant-
+Chlorepheniramine 1.chlorpheniramine + phenylephrine
Maleate chlorpheniramine increases and phenylephrine decreases sedation. Effect of interaction is not clear, use caution.
2.Dosing shedule of the ingredients are not compatible

158 Dextromethorphan + a, S.O. 862 (E)

bromhexine +Guaiphenesin Pharmacodynamically irrelevant-
1. Guiaphenesin: a mucolytic which increases mucus secretion should not given in combination with
antihistaminic with anti cholinergic properties, because due to anti cholinergic properties mucus secretions is
dried up.
2. Dextromethorphan: it decreases the cough impulse so expulsion of secretion would be hampered
3.Patients may need only one ingredient and use of FDC may lead to misuse.
4.Dosing shedule of the ingredients is incompatible.
159 Paracetamol + Loratadine + a, S.O. 863 (E)
phenylephrine + 1.Pharmacodynamically and phamacokinetically irrational FDC.
Dextromethorphan + 2.Patients may need only one ingredient and use of FDC may lead to misuse.
caffeine
160 Nimesulide + Phenylephrine a, S.O. 864 (E)
+ Ceffeine+ levocetirizine 1. Pharmacodynamically irrelevant-Patients may not need all the ingredients and use of FDC may lead to misuse
and adverse effects.
2.Pharmacokinetically irrelevant-different dosing shedule.
3. Nimesuilide- Safety concern
161 Azithromycin + a, S.O. 865 (E)
acebrophyline 1. Pharmacodynamically irrelevant-combining anti-bacterial with bronchodialator is not indicated.
2. Potential misuse as bronchodialator with anti-bacterial will increase the emergence of drug resistance to
azithromycin and its adverse effects .
162 Diphenhydramine +Terpine a, S.O. 866 (E)
+Ammonium Chloride Pharmacodynamically irrelevant.
+Sodium Chloride No published literature supporting the combination
+Menthol
163 Nimesulide+Paracetamol+C a, S.O. 867 (E)
etrizine +Phenylephrine 1. Nimesulide in combination has potential of misuse in indications for allergic conditions. Users who may not
be aware of this paracetamol content and may accidentally overdose when they take the multi- ingredient product
with other medicines also containing paracetamol.
2. There is pharmacokinetic incompatibility among the drugs.
3.Nimesuilide has documanted safety concern.
4. Hepatotoxic potential of both the drugs

Eccles, R., Fietze, I. and Rose, U.-B. (2014) Rationale for Treatment of Common Cold and Flu with Multi-
Ingredient Combination Products for Multi-Symptom Relief in Adults. Open Journal of Respiratory Diseases, 4,
73-82.

164 paracetamol+ loratadine + a, S.O. 868 (E)

dextromethophan + 1.Pharmacodynamically and phamacokinetically irrational FDC.
pseudoepheridine + caffeine 2.Patients may need only one ingredient and use of FDC may lead to misuse.
3.Dosing shedule of the ingredients is incompatible.
165 chlorpheniramine maleate+ S.O. 869 (E)
dextromethophan+ This FDC was dscussed earlier on 23.04.2014 by previous Committee and their comments are as under-
dextromethophan + The committee carefully examined the composition of each FDC, their indications as are available by the manufacturer’s
submission and also heard the manufacturer’s presentations and arguments.
guaiphenesin + ammonium
In view of the above, the committee observes the following:
chloride + menthol 1. The products of agenda 1 and 2 combines expectorants and cough suppressants. Thus the product does not target an
identifiable patient group. The medical rationale for combining the actives is insufficient.
2. The products of agenda 3 and 4 contain actives like levocetrizine (anti-histamine), phenylephrine (decongestant), ambroxol
(mucolytic-expectorant) and paracetamol; the indications are dry cough, allergic rhinitis, body ache and fever, upper respiratory
affections etc. The medical rationale for combining these actives is inadequate and the FDCs tend to accommodate diverse types
of patient situations and symptoms which usually do not co-exist. Thus a clear identifiable patient group for the FDCs was
missing.
3. However, it was also observed that the indications presented in the applications submitted and those at the time of
presentations were discrepant.
4. There is also apparent lack of pharmacokinetic and pharmacodynamic compatibility - while levocetrizine is usually given
once a day, phenylephrine or ambroxol would require more frequent administration. Use of Paracetamol in some of the referred
FDCs seems un- warranted, not to speak of the strength of the Paracetamol used (325 mg), which seems inadequate to treat fever
or body-ache in adult subjects.
5. Safety & Efficacy: In all the FDCs as referred to, no comments can be made on their safety or efficacy, since no data are
readily available. Some manufacturers submitted some feedback from prescribers on safety and effectiveness which on closer
scrutiny were found to be of very poor quality and could not be acceptable.
6. Nevertheless, the committee also takes note of the fact, most of such products are in the market for quite some time and the
manufacturers besides other things have argued in favor of better patient adherence and general acceptance by prescribers at
large.
7. Therefore, in fine, the committee recommends the manufacturers should be asked forthwith to 1. reconsider the rational basis
of their formulations and make fresh submissions justifying medical rationale, and then 2. to generate credible safety and efficacy
data for specific indication(s) following well designed scientific study protocol. Such protocols should be submitted before the
committee and with their concurrence the study may be recommended.
The whole of the above exercise for protocol submission should be completed within 3 months.

166 Chlorpheniramine a, S.O. 870 (E)

Maleate+Ammonium Pharmacodynamically irrelevant-
Chloride+Sodium Citrate 1. Chlorpheniramine :H1 antagonist are said to decrease rhinorrhea but the drying effect may do more harm
because of their tendency to induce somnolence
2. Ammonium Chloride: increase the mucus secretion in respiratory tract
167 Cetirizine +Phenylephrine a, S.O. 871 (E)
+Paracetamol +Zinc 1.Pharmacodynamically and phamacokinetically irrational FDC.
Gluconate 2.Patients may need only one ingredient and use of FDC may lead to misuse.
3.Dosing shedule of the ingredients is incompatible.
168 Ambroxol +Guaiphenesin a, S.O. 872 (E)
+Ammonium Chloride 1. Pharmacodynamically irrelevant-Patients may not need all the ingredients and use of FDC may lead to misuse
+Phenylephrine and adverse effects.
+Chlorpheniramine Maleate 2.Pharmacokinetically irrelevant-different dosing shedule
+Menthol
169 dextromethophen + a, S.O. 873 (E)
bromhexine + 1 Dosing schedule is incompatible.
chlorpheniramine maleate + 2. Ingredients will aggravate the adverse effects of sedation and drowsiness and also will interefere with the
guaiphenesin reflexes.
3.Centrally acting anti-tussive not to be combined with anti-histaminic drug.

170 levocetirizine + ambroxol + a, S.O. 874 (E)

phenylephrine 1. Pharmacodynamically irrelevant-Patients may not need all the ingredients and use of FDC may lead to misuse
+guaiphenesin and adverse effects.
2.Pharmacokinetically irrelevant-different dosing shedule
171 dextromethorphan + a, S.O. 875 (E)
chlorpheniramine + 1 Dosing schedule is incompatible.
chlorpheniramine maleate 2. Ingredients will aggravate the adverse effects of sedation and drowsiness and also will interefere with the
reflexes.
3.Centrally acting anti-tussive not to be combined with anti-histaminic drug.

172 cetirizine + ambroxol + a, S.O. 876 (E)

Guaiphenesin + ammonium 1.Pharmacodynamically and phamacokinetically irrational FDC.
chloride+ phenylephrine+ 2.Patients may need only one ingredient and use of FDC may lead to misuse.
menthol
173 chlorpheniramine + a, S.O. 877 (E)
phenylephrine + caffiene 1.Pharmacodynamically irrationale FDC.
2.Patients may need only one ingredient and use of FDC may lead to misuse.

174 dextromethorphan + a, S.O. 878 (E)

triprolidine + phenylephrine 1 Dosing schedule is incompatible.
2. Ingredients will aggravate the adverse effects of sedation and drowsiness and also will interefere with the
reflexes.
3.Centrally acting anti-tussive not to be combined with anti-histaminic drug.

175 Terpinhydrate+ a, S.O. 879 (E)

dextromethorphan + Pharmacodynamically irrelevant.
menthol No published literature supporting the combination.
176 dextromethorphan + a, S.O. 880 (E)
phenylephrine + zinc Pharmacodynamically irrelevant-
gluconate+ menthol 1 Dosing schedule is incompatible.
2. Ingredients will aggravate the adverse effects of sedation and drowsiness and also will interefere with the
reflexes.
177 chlorpheniramine + codeine 1 Dosing schedule is incompatible. S.O. 881 (E)
+ sodium citarte + menthol 2. Both the ingredients will aggravate the adverse effects of sedation and drowsiness and also will interefere with
syrup the reflexes.
3.Centrally acting anti-tussive not to be combined with anti-histaminic drug.
4.There is also a risk of abuse potential.
178 Enrofloxacin + bromhexin a, S.O. 882 (E)
Pharmacodynamically irrelevant-
1. Enrofloxacin is not approved for human use.
179 Bromhexine a, S.O. 883 (E)
+Dextromethorphan Pharmacodynamically irrelevant-
+Phenylephrine +Menthol 1. Dextromethorphan: it decreases the cough impulse so expulsion of secretion would be hampered
2. Bromhexine:a mucolytic which increases mucus secretion should not given in combination with antihistaminic
with anti cholinergic properties, because due to anti cholinergic properties mucus secretions is dried up.

180 Levofloxacin +Bromhexine a, S.O. 884 (E)

Pharmacodynamically irrelevant-
1. Patient may need only one ingredient and the use of FDC may lead to misuse.
2. Increased risk of emergence of drug resistance due to misuse of FDC .
181 Levocetirizine +Ranitidine a, S.O. 885 (E)
Pharmacodynamically irrelevant as both ingredients are indicated for different indications.
182 Levocetirizine a, S.O. 886 (E)
+Phenylephrine +Ambroxol Pharmacodynamically irrelevant-
+Guaiphenesin 1. Patients may not need all the ingredients and use of FDC may lead to misuse and adverse effects.
+Paracetamol 2.Pharmacokinetically irrelevant-different dosing shedule.
3.Potential drug interactions.
183 cetirizine + a, S.O. 887 (E)
dextromethorphan + 1.Pharmacodynamically and phamacokinetically irrational FDC.
phenylephrine + zinc 2.Patients may need only one ingredient and use of FDC may lead to misuse.
gluconate + paracetamol+ 3.Centrally acting anti-tussive not to be combined with anti-histaminic drug.
menthol
184 paracetamol+ a, S.O. 888 (E)
pseudoephedrine + 1 Dosing schedule is incompatible.
dextromethorphan + 2. Ingredients will aggravate the adverse effects of sedation and drowsiness and also will interefere with the
cetirizine reflexes.
3.Centrally acting anti-tussive not to be combined with anti-histaminic drug.

185 diphenhydamine + a, Pharmacodynamically irrelevant. S.O. 889 (E)

guaiphenesin + ammonium • Anticholinergic property of diphenhydramine will lead to drying up of secretions while mucolytics increase.
chloride + bromhexine
186 Chlorpheniramine a, S.O. 890 (E)
+Dextromethorphan 1 Dosing schedule is incompatible.
+Phenylephrine 2.Ingredients will aggravate the adverse effects of sedation and drowsiness and also will interefere with the
+Paracetamol reflexes.
3.Centrally acting anti-tussive not to be combined with anti-histaminic drug.

187 Dextromethorphen a, S.O. 891 (E)

+Promethazine 1 Dosing schedule is incompatible.
2. Ingredients will aggravate the adverse effects of sedation and drowsiness and also will interefere with the
reflexes.
3.Centrally acting anti-tussive not to be combined with anti-histaminic drug.

188 Diethylcabamazine a, S.O. 892 (E)

+Cetrizine +Guaiphenesin Pharmacodynamic irrelevant -
1. Patient may need only one ingredient and use of FDC may lead to misuse.
2.Guaiphenesin is not indicated for eosinophillia, as it is a mucolytic which increases mucus secretion and
should not be given in combination with antihistaminic with anti cholinergic properties.

189 Pseudoephedrine+Dextrome a, S.O. 893 (E)

thorphan +Cetirizine 1 Dosing schedule is incompatible.
2. Ingredients will aggravate the adverse effects of sedation and drowsiness and also will interefere with the
reflexes.
3.Centrally acting anti-tussive not to be combined with anti-histaminic drug.

190 Chlorpheniramine a, S.O. 894 (E)

+Phenylephrine 1 Dosing schedule is incompatible.
+Dextromethophan 2. Both the ingredients will aggravate the adverse effects of sedation and drowsiness and also will interefere with
+Menthol the reflexes.
3.Centrally acting anti-tussive not to be combined with anti-histaminic drug.

191 Ambroxol + Terbutaline + a, S.O. 895 (E)

Dextromethorphan 1. On the basis of current scientific understanding the FDC is pharmacodynamically irrelevant.
2. Use of Mucolytic alongwith anti-asthamatic drugs is liable to be misused as expectorant and exposing the
patients unnecessary to the drugs and their adverse effects.
192 Dextromethorphan a, S.O. 896 (E)
+Chlorpheniramine 1 Dosing schedule is incompatible.
+Guaiphenesin 2. Ingredients will aggravate the adverse effects of sedation and drowsiness and also will interefere with the
reflexes.
3.Centrally acting anti-tussive not to be combined with anti-histaminic drug.
193 Terbutaline +Bromhexine a, S.O. 897 (E)
+Guaiphenesin+Dextrometh Pharmacodynamically irrelevant-
orphan 1. Guiaphenesin: a mucolytic which increases mucus secretion should not given in combination with
antihistaminic with anti cholinergic properties, because due to anti cholinergic properties mucus secretions is
dried up.
2. Dextromethorphan: it decreases the cough impulse so expulsion of secretion would be hampered
3.Patients may need only one ingredient and use of FDC may lead to misuse.
4.Dosing shedule of the ingredients is incompatible.
194 Dextromethorphan a, S.O. 898 (E)
+Tripolidine Pharmacodynamically irrelevant-
+Phenylephirine 1 Dosing schedule is incompatible.
2. Ingredients will aggravate the adverse effects of sedation and drowsiness and also will interefere with the
reflexes.
3.Centrally acting anti-tussive not to be combined with anti-histaminic drug.

195 Paracetamol a, S.O. 899 (E)

+Dextromethorphan 1 Dosing schedule is incompatible.
+Chlorpheniramine 2. Ingredients will aggravate the adverse effects of sedation and drowsiness and also will interefere with the
reflexes.
3.Centrally acting anti-tussive not to be combined with anti-histaminic drug.

196 Pholcodine+Phenylephrine a, S.O. 900 (E)

+Promethazine 1 Dosing schedule is incompatible.
2. Ingredients will aggravate the adverse effects of sedation and drowsiness and also will interefere with the
reflexes.
3.Centrally acting anti-tussive not to be combined with anti-histaminic drug.

197 codeine + levocetirizine + 1 Dosing schedule is incompatible. S.O. 901 (E)

menthol 2. Both the ingredients will aggravate the adverse effects of sedation and drowsiness and also will interefere with
the reflexes.
3.Centrally acting anti-tussive not to be combined with anti-histaminic drug.
4.There is also a risk of abuse potential.
198 dextromethorphan + a, S.O. 902 (E)
ambroxol + guaifenesin + 1 Dosing schedule is incompatible.
phenylephrine + 2. Ingredients will aggravate the adverse effects of sedation and drowsiness and also will interefere with the
chlorpheniramine reflexes.
3.Centrally acting anti-tussive not to be combined with anti-histaminic drug.
199 Cetirizine +Phenylephrine a, S.O. 903 (E)
+ Dextromethorphan + 1.Pharmacodynamically and phamacokinetically irrational FDC.
Menthol 2.Patients may need only one ingredient and use of FDC may lead to misuse.
3.Centrally acting anti-tussive not to be combined with anti-histaminic drug.

200 Roxithromycin + a, S.O. 904 (E)

Serratiopeptidase Pharmacodynamically irrelevant-
May lead to misuse and drug resistance
201 Paracetamol +Phenylephrine a, S.O. 905 (E)
+Triprolidine 1.Pharmacodynamically and phamacokinetically irrational FDC.
2.Patients may need only one ingredient and use of FDC may lead to misuse.
3.Dosing shedule of the ingredients is incompatible.
202 Acetaminophen+Loratadine a, S.O. 906 (E)
+ambroxol +Phenylephrine 1.Pharmacodynamically and phamacokinetically irrational FDC.
2.Patients may need only one ingredient and use of FDC may lead to misuse.
203 Cetirizine a, S.O. 907 (E)
+Acetaminophen+Dextrome 1.Pharmacodynamically and phamacokinetically irrational FDC.
thorphan +Phenyephrine 2.Patients may need only one ingredient and use of FDC may lead to misuse.
+Zinc gluconate 3.Centrally acting anti-tussive not to be combined with anti-histaminic drug.

204 Diphenhydramine a, Pharmacodynamically irrelevant. S.O. 908 (E)

+Guaifenesin +Bromhexine • Anticholinergic property of diphenhydramine will lead to drying up of secretions while mucolytics increase.
+Ammonium Chloride
+Menthol
205 Chlopheniramine Maleate 1 Dosing schedule is incompatible. S.O. 909 (E)
+Codeine syrup 2. Both the ingredients will aggravate the adverse effects of sedation and drowsiness and also will interefere with
the reflexes.
3. Centrally acting anti-tussive not to be combined with anti-histaminic drug.
4.There is also a risk of abuse potential.
206 Cetirizine a, Pharmacodynamically irrelevant. S.O. 910 (E)
+Dextromethorphan +Zinc
Gluconate +Menthol 1.Patients may need only one ingredient and use of FDC may lead to misuse.
2..Pharmacokinetic incompatibility amongst ingredients.
3..Use of anti-histamine with centrally acting anti- tussive ingredient is not rationale
207 Paracetamol +Phenylephrine a, S.O. 911 (E)
+Desloratadine+Zinc 1.Pharmacodynamically and phamacokinetically irrational FDC.
Gluconate +Ambroxol 2.Patients may need only one ingredient and use of FDC may lead to misuse.
3.Dosing shedule of the ingredients is incompatible.
208 levocetirizine + montelukast a, S.O. 912 (E)
+ acebrophylline Pharmacodynamically irrelevant-
1. There is no published literature supporting FDC of three drugs.
2. Pharmacokinetic imcompatibilty.
209 dextromethorphan + S.O. 913 (E)
phenylephrine + ammonium This FDC was dscussed earlier on 23.04.2014 by previous Committee and their comments are as under-
chloride + menthol The committee carefully examined the composition of each FDC, their indications as are available by the manufacturer’s
submission and also heard the manufacturer’s presentations and arguments.
In view of the above, the committee observes the following:
1. The products of agenda 1 and 2 combines expectorants and cough suppressants. Thus the product does not target an
identifiable patient group. The medical rationale for combining the actives is insufficient.
2. The products of agenda 3 and 4 contain actives like levocetrizine (anti-histamine), phenylephrine (decongestant), ambroxol
(mucolytic-expectorant) and paracetamol; the indications are dry cough, allergic rhinitis, body ache and fever, upper respiratory
affections etc. The medical rationale for combining these actives is inadequate and the FDCs tend to accommodate diverse types
of patient situations and symptoms which usually do not co-exist. Thus a clear identifiable patient group for the FDCs was
missing.
3. However, it was also observed that the indications presented in the applications submitted and those at the time of
presentations were discrepant.
4. There is also apparent lack of pharmacokinetic and pharmacodynamic compatibility - while levocetrizine is usually given
once a day, phenylephrine or ambroxol would require more frequent administration. Use of Paracetamol in some of the referred
FDCs seems un- warranted, not to speak of the strength of the Paracetamol used (325 mg), which seems inadequate to treat fever
or body-ache in adult subjects.
5. Safety & Efficacy: In all the FDCs as referred to, no comments can be made on their safety or efficacy, since no data are
readily available. Some manufacturers submitted some feedback from prescribers on safety and effectiveness which on closer
scrutiny were found to be of very poor quality and could not be acceptable.
6. Nevertheless, the committee also takes note of the fact, most of such products are in the market for quite some time and the
manufacturers besides other things have argued in favor of better patient adherence and general acceptance by prescribers at
large.
7. Therefore, in fine, the committee recommends the manufacturers should be asked forthwith to 1. reconsider the rational basis
of their formulations and make fresh submissions justifying medical rationale, and then 2. to generate credible safety and efficacy
data for specific indication(s) following well designed scientific study protocol. Such protocols should be submitted before the
committee and with their concurrence the study may be recommended.
The whole of the above exercise for protocol submission should be completed within 3 months.

210 Dextromethorphan a, S.O. 914 (E)

+bromhexine Pharmacodynamically irrelevant-
+Guaiphenesin+menthol 1. Guiaphenesin: a mucolytic which increases mucus secretion should not given in combination with
antihistaminic with anti cholinergic properties, because due to anti cholinergic properties mucus secretions is
dried up.
2. Dextromethorphan: it decreases the cough impulse so expulsion of secretion would be hampered
3.Patients may need only one ingredient and use of FDC may lead to misuse.
4.Dosing shedule of the ingredients is incompatible.
211 Acrivastine+ Paracetamol + a, S.O. 915 (E)
Caffeine + Phenylephrine 1.Pharmacodynamically and phamacokinetically irrational FDC.
2.Patients may need only one ingredient and use of FDC may lead to misuse.
212 Naphazoline +carboxy a, S.O. 916 (E)
Methyl cellulose +Menthol Pharmacodynamically irrelevant-
+Camphor +Phenylephrine 1. Therapeutic area not clear
2. Multiple ingredients with diverse pharmacological profile susceptible to pharmaceutically incompatibility

213 Dextromethorphan a, S.O. 917 (E)

+Cetirizine 1 Dosing schedule is incompatible.
2. Ingredients will aggravate the adverse effects of sedation and drowsiness and also will interefere with the
reflexes.
3.Centrally acting anti-tussive not to be combined with anti-histaminic drug.

214 nimesulide + paracetamol + a, S.O. 918 (E)

levocetirizine + 1. Pharmacodynamically irrelevant-Patients may not need all the ingredients and use of FDC may lead to misuse
phenylephrine + caffeine and adverse effects.
2.Pharmacokinetically irrelevant-different dosing shedule.
3. Nimesuilide- Safety concern
215 Terbutaline +Ambroxol a, S.O. 919 (E)
+Guaiphenesin+Zinc+Ment 1. On the basis of current scientific understanding the FDC is pharmacodynamically irrelevant.
hol 2. Use of Mucolytic alongwith anti-asthamatic drugs is liable to be misused as expectorant and exposing the
patients unnecessary to the drugs and their adverse effects.

216 Codeine +Chlorpheniramine 1 Dosing schedule is incompatible. S.O. 920 (E)

+Alcohol syrup 2. Both the ingredients will aggravate the adverse effects of sedation and drowsiness and also will interefere with
the reflexes.
3. Centrally acting anti-tussive not to be combined with anti-histaminic drug.
4.There is also a risk of abuse potential.
217 Dextromethorphan a, S.O. 921 (E)
+Phenylephrine Pharmacodynamically irrelevant-
+Guaifenesin+Triprolidine 1. Guiaphenesin: a mucolytic which increases mucus secretion should not given in combination with
antihistaminic with anti cholinergic properties, because due to anti cholinergic properties mucus secretions is
dried up.
2. Dextromethorphan: it decreases the cough impulse so expulsion of secretion would be hampered
3.Patients may need only one ingredient and use of FDC may lead to misuse.
4.Dosing shedule of the ingredients is incompatible.
218 Ammomium a, S.O. 922 (E)
Chloride+Bromhexine Pharmacodynamically irrelevant-
+Dextromethorphan 1. Bromhexine: a mucolytic which increases mucus secretion should not given in combination with
antihistaminic with anti cholinergic properties, because due to anti cholinergic properties mucus secretions is
dried up.
2. Dextromethorphan decreases the cough impulse so expulsion of secretion would be hampered

219 Diethylcarbamazine a, S.O. 923 (E)

+Cetirizine +Ambroxol Pharmacodynamic irrelevant-
1 .Patients may need only one ingredient and use of FDC may lead to misuse.
2. Ambroxol is not indicated for eosinophillia,as it is a mucolytic which increases mucus secreation and should
not be given in combination with anti histaminic with anti cholinergic properties.

220 Ethylmorphine + Noscapine a, Pharmacodynamically irrelevant. 1 Dosing schedule is incompatible. S.O. 924 (E)
+ Chlorpheniramine Maleate 2. Ingredients will aggravate the adverse effects of sedation and drowsiness and also will interefere with the
reflexes.
3. Centrally acting anti-tussive not to be combined with anti-histaminic drug.

221 Cetirizine a, Pharmacodynamically S.O. 925 (E)

+Dextromethorphan 1. Ambroxol: a mucolytic which increases mucus secretion should not given in combination with antihistaminic
+Ambroxol with anti cholinergic properties, because due to anti cholinergic properties mucus secretions is dried up.
2. Dextromethorphan decreases the cough impulse so expulsion of secretion would be hampered
3.Patients may need only one ingredient and use of FDC may lead to misuse.
4.Pharmacokinetic incompatibility amongst ingredients.
5.Use of anti-histamine with centrally acting anti- tussive ingredient is not rationale
222 Bromhexine a, S.O. 926 (E)
+Dextromethorphan Pharmacodynamically irrelevant-
+Ammonium Chloride 1. Dextromethorphan: it decreases the cough impulse so expulsion of secretion would be hampered
+Menthol 2. Bromhexine:a mucolytic which increases mucus secretion should not given in combination with antihistaminic
with anti cholinergic properties, because due to anti cholinergic properties mucus secretions is dried up.

223 Ambroxol + Guaifenesin + a, S.O. 927 (E)

Phenylephrine + 1. Pharmacodynamically irrelevant-Patients may not need all the ingredients and use of FDC may lead to misuse
Chlorpheniramine and adverse effects.
2.Pharmacokinetically irrelevant-different dosing shedule
224 Paracetamol +Phenylephrine a, S.O. 928 (E)
+Chlorpheniramine +Zinc 1.Pharmacodynamically and phamacokinetically irrational FDC.
Gluconate 2.Patients may need only one ingredient and use of FDC may lead to misuse.
3.Dosing shedule of the ingredients is incompatible.
225 Dextromethorphan a, S.O. 929 (E)
+Phenylephrine +Cetirizine 1 Dosing schedule is incompatible.
+Paracetamol +Caffeine 2. Ingredients will aggravate the adverse effects of sedation and drowsiness and also will interefere with the
reflexes.
3.Centrally acting anti-tussive not to be combined with anti-histaminic drug.

226 Dextromethophan a, S.O. 930 (E)

+Chlorpheniramine 1 Dosing schedule is incompatible.
+Guaifenesin +Ammonium 2. Ingredients will aggravate the adverse effects of sedation and drowsiness and also will interefere with the
Chloride reflexes.
3.Centrally acting anti-tussive not to be combined with anti-histaminic drug.

227 Levocetirizine a, S.O. 931 (E)

+Dextromethorphan +Zinc 1 Dosing schedule is incompatible.
2. Ingredients will aggravate the adverse effects of sedation and drowsiness and also will interefere with the
reflexes.
3.Centrally acting anti-tussive not to be combined with anti-histaminic drug.

228 Paracetamol +Phenylephrine a, S.O. 932 (E)

+Levocetirizine +Caffeine 1.Pharmacodynamically and phamacokinetically irrational FDC.
2.Patients may need only one ingredient and use of FDC may lead to misuse.
3.Dosing shedule of the ingredients is incompatible.
229 Chlorpheniramine a, S.O. 933 (E)
+Ammonium Chloride Pharmacodynamically irrelevant-
+Sodium Chloride 1. Chlorpheniramine :H1 antagonist are said to decrease rhinorrhea but the drying effect may do more harm
because of their tendency to induce somnolence
2. Ammonium Chloride: increase the mucus secretion in respiratory tract
230 Paracetamol a, S.O. 934 (E)
+Dextromethorphan 1 Dosing schedule is incompatible.
+Bromhexine 2. Ingredients will aggravate the adverse effects of sedation and drowsiness and also will interefere with the
+Phenylephrine reflexes.
+Diphenhydramine 3.Centrally acting anti-tussive not to be combined with anti-histaminic drug.
4.Paracetamol dose is subtherapeutic.

231 Salbutamol +Bromhexine a, S.O. 935 (E)

+Guaiphenesin +Menthol 1. On the basis of current scientific understanding the FDC is pharmacodynamically irrelevant.
2. Use of Mucolytic alongwith anti-asthamatic drugs is liable to be misused as expectorant and exposing the
patients unnecessary to the drugs and their adverse effects.
232 Chlorpheniramine a, S.O. 936 (E)
+Ammonium Chloride Pharmacodynamically irrelevant-
+Noscapine +Sodium 1. Chlorpheniramine :H1 antagonist are said to decrease rhinorrhea but the drying effect may do more harm
Citrate because of their tendency to induce somnolence
2. Ammonium Chloride: increase the mucus secretion in respiratory tract
233 Cetirizine a, S.O. 937 (E)
+Dextromethorphan
+Bromhexine +Guaifenesin 1. Dextromethorphan: it decreases the cough impulse so expulsion of secretion would be hampered
2. Bromhexine:a mucolytic which increases mucus secretion should not given in combination with antihistaminic
with anti cholinergic properties, because due to anti cholinergic properties mucus secretions is dried up.
3.Pharmacokinetic incompatibility amongst ingredients.
4.Use of anti-histamine with centrally acting anti- tussive ingredient is not rationale

234 Diethyl Carbamazine a, S.O. 938 (E)

+Chlorpheniramine Pharmacodynamic irrelevant -
+Guaifenesin 1. Patient may need only one ingredient and use of FDC may lead to misuse.
2.Guaiphenesin is not indicated for eosinophillia, as it is a mucolytic which increases mucus secretion and
should not be given in combination with antihistaminic with anti cholinergic properties.

235 Ketotifen +Cetirizine a, S.O. 939 (E)

1. No supporting published literature available on the combination.
2. Pharmakokinetic incompatibility,
236 Terbutaline +Bromhexine a, S.O. 940 (E)
+Etofylline 1. On the basis of current scientific understanding the FDC is pharmacodynamically irrelevant.
2. Use of Mucolytic alongwith anti-asthamatic drugs is liable to be misused as expectorant and exposing the
patients unnecessary to the drugs and their adverse effects.

237 Ketotifen +Theophylline a, S.O. 941 (E)

Pharmacodynamically irrelevant-
1. Theophylline has narrow therapeutic index, and in FDC the toxicity of drug is major concern.
2. Pharmakokinetic incompatibility.
238 Ambroxol +Salbutamol a, S.O. 942 (E)
+Theophylline 1. On the basis of current scientific understanding the FDC is pharmacodynamically irrelevant.
2. Use of Mucolytic alongwith anti-asthamatic drugs is liable to be misused as expectorant and exposing the
patients unnecessary to the drugs and their adverse effects.

239 Cetirizine +Nimesulide a, S.O. 943 (E)

+Phenylephrine 1.Pharmacodynamically irrelevant as different ingredients have different therapeutic indication
2. Nimesulide: safety concern
240 Chloropheniramine a, S.O. 944 (E)
+Phenylephrine+Paracetamo 1.Pharmacodynamically and phamacokinetically irrational FDC.
l+Zinc Gluconate 2.Patients may need only one ingredient and use of FDC may lead to misuse.
3.Dosing shedule of the ingredients is incompatible.
241 Acetaminophen+Guaifenesi a, S.O. 945 (E)
n+Dextromethorphan 1. Use of anti-histamine with centrally acting anti- tussive ingredient is not rationale
+Chlorpheniramine 2. Patients may need only one ingredient and use of FDC may lead to misuse.
3.Different mechanism of action without synergistic action.
4.Also the Acetaminophen, an antipyretic, is not indicated in the cough syrup. (04.01.2016)
242 Cetirizine a, S.O. 946 (E)
+Dextromethorphan 1.Pharmacodynamically and phamacokinetically irrational FDC.
+Phenylephrine +Tulsi 2.Patients may need only one ingredient and use of FDC may lead to misuse.
3.Use of anti-histamine with centrally acting anti- tussive ingredient is not rationale

243 Cetirizine +Phenylephrine a, S.O. 947 (E)

+Paracetamol+Ambroxol 1.Pharmacodynamically and phamacokinetically irrational FDC.
+Caffeine 2.Patients may need only one ingredient and use of FDC may lead to misuse.

244 Guaifenesin+Dextromethorp a, S.O. 948 (E)

han Pharmacodynamically irrelevant-
1. Guaiphenesin :a mucolytic which increases mucus secretion.
2. Dextromethorphan: it decreases the cough impulse so expulsion of secretion would be hampered (04.01.2016)

245 Levocetirizine +Paracetamol a, S.O. 949 (E)

+Phenylephirine +Caffeine 1. Pharmacodynamically irrelevant-Patients may not need all the ingredients and use of FDC may lead to misuse
and adverse effects.
2.Pharmacokinetically irrelevant-different dosing shedule.
246 Caffeine +Paracetamol a, S.O. 950 (E)
+Phenylephrine + 1.Pharmacodynamically and phamacokinetically irrational FDC.
Chlorpheniramine 2.Patients may need only one ingredient and use of FDC may lead to misuse.
3.Dosing shedule of the ingredients is incompatible.
247 Ketotifen +Levocetrizine a, S.O. 951 (E)
1. No supporting published literature available on the combination.
2. Pharmakokinetic incompatibility
248 Paracetamol +Levocetirizine a, S.O. 952 (E)
+Phenylephirine +Zinc 1. Paracetamol dose is subtherapeutic.
Gluconate 2. Pharmacokinetic incompatibility.
3. Potential for drug-drug interaction.
4. No published literature supporting addition of Zinc in this FDC.
249 Paracetamol +Phenylephrine a, S.O. 953 (E)
+Triprolidine +Caffeine 1.Pharmacodynamically and phamacokinetically irrational FDC.
2.Patients may need only one ingredient and use of FDC may lead to misuse.
3.Dosing shedule of the ingredients is incompatible.
250 Caffeine +Paracetamol a, S.O. 954 (E)
+Phenylephrine +Cetirizine 1.Pharmacodynamically and phamacokinetically irrational FDC.
2.Patients may need only one ingredient and use of FDC may lead to misuse.

251 Dextromethorphan a, S.O. 955 (E)

+Phenylephirine Pharmacodynamically irrelevant-
+Guaifenesin 1. Guiaphenesin: a mucolytic which increases mucus secretion should not given in combination with
antihistaminic with anti cholinergic properties, because due to anti cholinergic properties mucus secretions is
dried up.
2. Dextromethorphan: it decreases the cough impulse so expulsion of secretion would be hampered
3.Patients may need only one ingredient and use of FDC may lead to misuse.
4.Dosing shedule of the ingredients is incompatible.
252 Ambroxol + Levocetirizine a, S.O. 956 (E)
+ Phenylephrine + 1. Pharmacodynamically irrelevant-Patients may not need all the ingredients and use of FDC may lead to misuse
Guaiphenesin + Menthol and adverse effects.
2.Pharmacokinetically irrelevant-different dosing shedule
253 Pseudoephedrine a, S.O. 957 (E)
+Cetirizine Pharmacodynamically irrelevant.
1.Both increase the sedation as adverse effect.
2.Dosing schedule is incompatible.
254 Dextromethorphan a, S.O. 958 (E)
+Chlorpheniramine 1 Dosing schedule is incompatible.
+Ammonium Chloride 2. Ingredients will aggravate the adverse effects of sedation and drowsiness and also will interefere with the
+Menthol reflexes.
3.Centrally acting anti-tussive not to be combined with anti-histaminic drug.

255 Paracetamol +Caffeine a, S.O. 959 (E)

+Phenylephrine 1.Pharmacodynamically and phamacokinetically irrational FDC.
+Chlorpheniramine 2.Patients may need only one ingredient and use of FDC may lead to misuse.
3.Dosing shedule of the ingredients is incompatible.
256 Salbutamol +Aminophylline a, S.O. 960 (E)
+Guaifenesin 1. On the basis of current scientific understanding the FDC is pharmacodynamically irrelevant.
2. Use of Mucolytic alongwith anti-asthamatic drugs is liable to be misused as expectorant and exposing the
patients unnecessary to the drugs and their adverse effects.

257 Salbutamol +Thoephylline a, S.O. 961 (E)

+Bromhexine 1. On the basis of current scientific understanding the FDC is pharmacodynamically irrelevant.
2. Use of Mucolytic alongwith anti-asthamatic drugs is liable to be misused as expectorant and exposing the
patients unnecessary to the drugs and their adverse effects.

258 Chlorpheniramine a, S.O. 962 (E)

+Dextromethorphan 1 Dosing schedule is incompatible.
+Guaifenesin 2. Both the ingredients will aggravate the adverse effects of sedation and drowsiness and also will interefere with
+Phenylephrine the reflexes.
3.Centrally acting anti-tussive not to be combined with anti-histaminic drug.

259 Caffeine + Paracetamol+ a, S.O. 963 (E)

Chlorpheniramine 1.Pharmacodynamically and phamacokinetically irrational FDC.
2.Patients may need only one ingredient and use of FDC may lead to misuse.
3.Dosing shedule of the ingredients is incompatible.

260 Ammonium a, S.O. 964 (E)

Chloride+Dextromethophan 1. Pharmacodynamically irrelevant.
+Cetirizine +Menthol 2. Pharmacokinetic incompatiblity amongst the ingredients
3.Use of anti-histamine with centrally acting anti- tussive ingredient is not rationale
261 Dextromethorphan a, S.O. 965 (E)
+Paracetamol+Cetirizine 1 Dosing schedule is incompatible.
+Phenylephrine 2. Ingredients will aggravate the adverse effects of sedation and drowsiness and also will interefere with the
reflexes.
3.Centrally acting anti-tussive not to be combined with anti-histaminic drug.

262 Chlorpheniramine +Terpin a, S.O. 966 (E)

+Antimony Potassium Pharmacodynamically irrelevant-
Tartrate+Ammonium 1. Chlorpheniramine :H1 antagonist are said to decrease rhinorrhea but the drying effect may do more harm
chloride+Sodium because of their tendency to induce somnolence
Citrate+Menthol 2. Ammonium Chloride: increase the mucus secretion in respiratory tract
263 Terbutaline a, S.O. 967 (E)
Sulphate+Etofylline+Ambro 1. On the basis of current scientific understanding the FDC is pharmacodynamically irrelevant.
xol 2. Use of Mucolytic alongwith anti-asthamatic drugs is liable to be misused as expectorant and exposing the
patients unnecessary to the drugs and their adverse effects.

264 Paracetamol +Codeine a, S.O. 968 (E)

+Chlorpheniramine 1 Dosing schedule is incompatible.
2. Both the ingredients will aggravate the adverse effects of sedation and drowsiness and also will interefere with
the reflexes.
3.Paracetamol dose is subtherapeutic.
4.There is also a risk of abuse potential.

265 Paracetamol a, S.O. 969 (E)

+Pseudoephedrine 1.Pharmacodynamically and phamacokinetically irrational FDC.
+Cetirizine +Caffeine 2.Patients may need only one ingredient and use of FDC may lead to misuse.
3.Caffeine is CNS stimulant where as Pseudoephedrine leads to sedation.
4.Dosing shedule of the ingredients is incompatible.

266 Chlorpheniramine a, S.O. 970 (E)

+Ammonium Chloride Pharmacodynamically irrelevant-
+Menthol 1. Chlorpheniramine :H1 antagonist are said to decrease rhinorrhea but the drying effect may do more harm
because of their tendency to induce somnolence
2. Ammonium Chloride: increase the mucus secretion in respiratory tract
267 N-Acetyl Cysteine + a, S.O. 971 (E)
Ambroxol + Phenylephrine Pharmacodynamically irrelevant-
+ Levocetirizine 1 Dosing schedule is incompatible.
2. Ingredients will aggravate the adverse effects of sedation and drowsiness and also will interefere with the
reflexes.
3. Potential for Drug-Drug interaction.
4. Indication of N-acetyl cystine in the FDC is irrelevant.

268 Dextromethorphan a, S.O. 972 (E)

+Phenylephrine Pharmacodynamically irrelevant-
+Tripolidine +Menthol 1 Dosing schedule is incompatible.
2. Ingredients will aggravate the adverse effects of sedation and drowsiness and also will interefere with the
reflexes.
3.Centrally acting anti-tussive not to be combined with anti-histaminic drug.

269 Salbutamol +Cetirizine a, S.O. 973 (E)

+Ambroxol 1. On the basis of current scientific understanding the FDC is pharmacodynamically irrelevant.
2. Use of Mucolytic alongwith anti-asthamatic drugs is liable to be misused as expectorant and exposing the
patients unnecessary to the drugs and their adverse effects.

270 Dextromethorphan a, S.O. 974 (E)

+Phenylephrine Pharmacodynamically irrelevant-
+Bromhexine 1 Dosing schedule is incompatible.
+Guaifenesin+ 2. Ingredients will aggravate the adverse effects of sedation and drowsiness and also will interefere with the
Chlorpheniramine reflexes.
3.Centrally acting anti-tussive not to be combined with anti-histaminic drug.

271 Nimesulide +Cetirizine a, S.O. 975 (E)

+Phenylephrine 1.Pharmacodynamically and phamacokinetically irrational FDC.
2.Patients may need only one ingredient and use of FDC may lead to misuse.
3.Potential for nimesulide toxicity and misuse in FDC.
4.Potential for drug-drug interaction.

272 Naphazoline a, S.O. 976 (E)

+Chlorpheniramine +Zinc Pharmacodynamically irrelevant-
Sulphate +Boric Acid 1. Therapeutic area not clear
Ip+Sodium chloride 2. Multiple ingredients with diverse pharmacological profile susceptible to pharmaceutically incompatibility
+chlorobutol
273 Paracetamol+Bromhexine a, S.O. 977 (E)
+Phenylephrine Pharmacodynamically irrelevant.
+Chlorpheniramine 1.Mucolytic increases mucus secretion and antihistaminic with anti cholinergic properties dry up secretions.
+Guaifenesin 2.Dosing schedule is incompatible.
3. Paracetamol dose is subtherapeutic.

274 Salbutamoll+Bromhexine a, S.O. 978 (E)

1. On the basis of current scientific understanding the FDC is pharmacodynamically irrelevant.
2. Use of Mucolytic alongwith anti-asthamatic drugs is liable to be misused as expectorant and exposing the
patients unnecessary to the drugs and their adverse effects.

275 Dextromethorphan a, S.O. 979 (E)

+Phenylephrine 1 Dosing schedule is incompatible.
+Guaifenesin +Cetirizine 2. Ingredients will aggravate the adverse effects of sedation and drowsiness and also will interefere with the
+Acetaminophen reflexes.
3.Centrally acting anti-tussive not to be combined with anti-histaminic drug.

276 Guaifenesin+ Bromhexine + a, S.O. 980 (E)

Chlorpheniramine + Pharmacodynamically irrelevant-
Paracetamol 1. Guaiphenesin:a mucolytic which increases mucus secretion should not given in combination with
antihistaminic with anti cholinergic properties, because due to anti cholinergic properties mucus secretions is
dried up.
2. paracetamol : addition of paracetamol express the consumers to the hepatotoxic effect of antipyretic
unnecessarily
3. Chlorpheniramine :H1 antagonist are said to decrease rhinorrhea but the drying effect may do more harm
because of their tendency to induce somnolence
4.All ingredients present in the FDC have different indications.

277 Chlorpheniramine a, S.O. 981 (E)

+Ammonium Chloride Pharmacodynamically irrelevant-
+Chloroform +Menthol 1. Chlorpheniramine :H1 antagonist are said to decrease rhinorrhea but the drying effect may do more harm
because of their tendency to induce somnolence
2. Ammonium Chloride: increase the mucus secretion in respiratory tract

278 Salbutamol +Choline a, S.O. 982 (E)

Theophylinate +Ambroxol 1. On the basis of current scientific understanding the FDC is pharmacodynamically irrelevant.
2. Use of Mucolytic alongwith anti-asthamatic drugs is liable to be misused as expectorant and exposing the
patients unnecessary to the drugs and their adverse effects.
279 Chlorpheniramine 1 Dosing schedule is incompatible. S.O. 983 (E)
+Codeine phosphate 2. Both the ingredients will aggravate the adverse effects of sedation and drowsiness and also will interefere with
+Menthol syrup the reflexes. 3.Centrally acting anti-tussive not to be combine with anti-histaminic drug
4.There is also a risk of abuse potential.

280 Pseudoephedrine a, S.O. 984 (E)

+Bromhexine Pharmacodynamically irrelevant.
1.Mucokinetic increases mucus secretion and decongestant will dry up secretions.
2.Dosing schedule is incompatible.

281 Cetirizine +Phenylephrine a, S.O. 985 (E)

+Paracetamol +Caffeine 1.Pharmacodynamically and phamacokinetically irrational FDC.
+Nimesulide 2.Patients may need only one ingredient and use of FDC may lead to misuse.
3.Dosing shedule of the ingredients is incompatible.

282 Dextromethorphan a, S.O. 986 (E)

+Cetirizine +Guaifenesin 1 Dosing schedule is incompatible.
+Ammonium Chloride 2. Ingredients will aggravate the adverse effects of sedation and drowsiness and also will interefere with the
reflexes.
3.Centrally acting anti-tussive not to be combined with anti-histaminic drug.

283 Ambroxol + Salbutamol + a, S.O. 987 (E)

Choline Theophyllinate + 1. On the basis of current scientific understanding the FDC is pharmacodynamically irrelevant.
Menthol 2. Use of Mucolytic alongwith anti-asthamatic drugs is liable to be misused as expectorant and exposing the
patients unnecessary to the drugs and their adverse effects.
284 Paracetamol a, S.O. 988 (E)
+Chlorpheniramine Pharmacodynamically irrelevant.
+Ambroxol +Guaifenesin • Mucolytic increases mucus secretion and antihistaminic with anti cholinergic properties dry up secretions.
+Phenylephrine • Dosing schedule is incompatible.

285 Chlorpheniramine +Vasaka a, S.O. 989 (E)

+Tolubalsm +Ammonium Pharmacodynamically irrelevant-
Chloride +Sodium Citrate 1. Chlorpheniramine :H1 antagonist are said to decrease rhinorrhea but the drying effect may do more harm
+Menthol because of their tendency to induce somnolence
2. Ammonium Chloride: increase the mucus secretion in respiratory tract.
286 Bromhexine +Cetrizine a, S.O. 990 (E)
+Phenylephrine 1.Pharmacologically no synergistic effect
+Guaifenesin +Menthol 2. Multiple ingredients with diverse pharmacological profile susceptible to pharmaceutically incompatibility.
3. Pharmacokinetically incompatibiliy.

287 Dextromethorphan a, S.O. 991 (E)

+Ambroxol +Ammonium 1 Dosing schedule is incompatible.
Chloride +Chlorpheniramine 2. Ingredients will aggravate the adverse effects of sedation and drowsiness and also will interefere with the
+Menthol reflexes.
3.Centrally acting anti-tussive not to be combined with anti-histaminic drug.

288 Dextromethorphan a, S.O. 992 (E)

+Phenylephrine +Cetirizine Pharmacodynamically irrelevant-
+Zinc +Menthol 1 Dosing schedule is incompatible.
2. Ingredients will aggravate the adverse effects of sedation and drowsiness and also will interefere with the
reflexes.
3.Centrally acting anti-tussive not to be combined with anti-histaminic drug.

289 Terbutaline + N-Acetyl L- a, S.O. 993 (E)

Cysteine + Guaifenesin 1. On the basis of current scientific understanding the FDC is pharmacodynamically irrelevant.
2. Use of Mucolytic alongwith anti-asthamatic drugs is liable to be misused as expectorant and exposing the
patients unnecessary to the drugs and their adverse effects.

290 Calcium Gluconate a, S.O. 994 (E)

+Levocetirizine Pharmacodynamically irrelevant-
1.Each ingredients have different indication.
2.This combination does not follow the concept and purpose of FDC

291 Paracetamol a, S.O. 995 (E)

+Levocetirizine+Pseudoeph 1. Paracetamol dose high
edrine 2. Pharmacokinetic incompatibility.
3. Potential for drug-drug interaction.

292 Salbutamol +Choline a, S.O. 996 (E)

Theophylinate 1. On the basis of current scientific understanding the FDC is pharmacodynamically irrelevant.
+Carbocisteine 2. Use of Mucolytic alongwith anti-asthamatic drugs is liable to be misused as expectorant and exposing the
patients unnecessary to the drugs and their adverse effects.
293 Chlorpheniramine +Vitamin a, S.O. 997 (E)
C Pharmacodynamically irrelevant FDC

294 Calcium Gluconate a, S.O. 998 (E)

+Chlorpheniramine Pharmacodynamically irrelevant-
+Vitamin C 1.Each ingredients have different indication.
2.This combination does not follow the concept and purpose of FDC

295 Chlorpheniramine+Paraceta a, S.O. 999 (E)

mol +Pseudoephedrine 1.Pharmacodynamically irrationale FDC.
+Caffeine 2.Patients may need only one ingredient and use of FDC may lead to misuse.
3.Caffeine is CNS stimulant where as Pseudoephedrine leads to sedation.

296 Guaifenesin +Bromhexine a, S.O. 1000 (E)

+Chlorpheniramine Pharmacodynamically irrelevant-
+Phenylephrine 1. Guaiphenesin :a mucolytic which increases mucus secretion should not given in combination with
+Paracetamol antihistaminic with anti cholinergic properties, because due to anti cholinergic properties mucus secretions is
+Serratiopeptidase (as dried up.
enteric coated 2. Chlorpheniramine :H1 antagonist are said to decrease rhinorrhea but the drying effect may do more harm
granules)10000 SP Units because of their tendency to induce somnolence
3. paracetamol : as cough and cold not allows accompanied by fever, addition of paracetamol express the
consumers to the hepatotoxic effect of antipyretic unnecessarily
4. All ingredients have different therapeutic indications.
297 Paracetamol +Pheniramine a, S.O. 1001 (E)
Pharmacodynamically irrelevant-
1. Both ingredients have different indications.
2. Misuse and toxicity of paracetamol.
298 Betamethasone +Fusidic a, S.O. 1002 (E)
Acid+Gentamycin Pharmacodynamically irrelevant-
+Tolnaftate+Iodochlorhydro 1.Each ingredients of FDC has different therapeutic indication and is at variance from the concept and purpose of
xyquinoline(ICHQ) FDC.
2. Combining antibiotics , antifungal, steroid in the present FDC is liable to be misused and emergence of
resistance and adverse effects 3.use of steroid in case of fungal infection might actually worsen the treatment as it
encourages fungal growth.No study is found supporting the combined use of an anti bacterial with an anti fungal
ingredient.
299 Clobetasol a, S.O. 1003 (E)
+Ofloxacin+Miconazole Pharmacodynamically irrelevant-
+Zinc Sulphate 1.Each ingredients of FDC has different therapeutic indication and is at variance from the concept and purpose of
FDC.
2. Combining antibiotics , antifungal, steroid in the present FDC is liable to be misused and emergence of
resistance and adverse effects 3.use of steroid in case of fungal infection might actually worsen the treatment as it
encourages fungal growth.No study is found supporting the combined use of an anti bacterial with an anti fungal
ingredient.
300 Clobetasole +Gentamicin a, S.O. 1004 (E)
+Miconazole +Zinc Pharmacodynamically irrelevant-
Sulphate 1.Each ingredients of FDC has different therapeutic indication and is at variance from the concept and purpose of
FDC.
2. Combining antibiotics , antifungal, steroid in the present FDC is liable to be misused and emergence of
resistance and adverse effects 3.use of steroid in case of fungal infection might actually worsen the treatment as it
encourages fungal growth.No study is found supporting the combined use of an anti bacterial with an anti fungal
ingredient.
301 levocetirizine + ambroxol + a, S.O. 1005 (E)
phenylephrine + 1 Dosing schedule is incompatible.
paracetamol 2. Patients may need only one or two ingredients and use of FDC may lead to misuse.
302 Permethrin + Cetrimide + a, S.O. 1006 (E)
Menthol 1.This FDC has no therapeutic value.

303 beclomethasone + a, S.O. 1007 (E)

clotimazole + neomycin + Pharmacodynamically irrelevant-
iodochlorohydroxyquinone 1.Each ingredients of FDC has different therapeutic indication and is at variance from the concept and purpose of
FDC.
2. Combining antibiotics , antifungal, steroid ,iodochlorohydroxyquinone in the present FDC is liable to be
misused and emergence of resistance and adverse effects 3.use of steroid in case of fungal infection might
actually worsen the treatment as it encourages fungal growth.No study is found supporting the combined use of
an anti bacterial with an anti fungal ingredient.

304 Neomycin + Doxycycline a, S.O. 1008 (E)

Pharmacodynamically irrelevant-
1. Patient may need only one ingredient
2. Drug misuse should not be there for diagnostic uncertainty
3. Inadvertent use of antimicrobials may lead to emergence of resistence
4. No published literature supporting this combination of products found
305 Ciprofloxacin + a, S.O. 1009 (E)
Fluocinolone + Pharmacodynamically irrelevant-
Clotrimazole + Neomycin + 1.Each ingredients of FDC has different therapeutic indication and is at variance from the concept and purpose of
Chlorocresol FDC.
2. Combining two antibiotics , antifungal, steroid in the present FDC is liable to be misused and emergence of
resistance and adverse effects.
3.NO study is found supporting the combined use of ingredients in this FDC.
306 Clobetasol + Ofloxacin + a, S.O. 1010 (E)
Ketoconazole + Zinc Pharmacodynamically irrelevant-
Sulphate 1.Each ingredients of FDC has different therapeutic indication and is at variance from the concept and purpose of
FDC.
2. Combining antibiotics , antifungal, steroid in the present FDC is liable to be misused and emergence of
resistance and adverse effects 3.use of steroid in case of fungal infection might actually worsen the treatment as it
encourages fungal growth.No study is found supporting the combined use of an anti bacterial with an anti fungal
ingredient.
307 Betamethasone a, S.O. 1011 (E)
+Gentamicin +Tolnaftate Pharmacodynamically irrelevant-
+Iodochlorhydroxyquinoline 1.Each ingredients of FDC has different therapeutic indication and is at variance from the concept and purpose of
FDC.
2. Combining antibiotics , antifungal, steroid ,iodochlorohydroxyquinone in the present FDC is liable to be
misuse and emergence of resistance and adverse effects 3.Use of steroid in case of fungal infection might actually
worsen the treatment as it encourages fungal growth.No study is found supporting the combined use of an anti
bacterial with an anti fungal ingredient.

308 Clobetasol +Gentamicin a, S.O. 1012 (E)

+Tolnaftate Pharmacodynamically irrelevant-
+Idochlorhydroxyquinone 1.Each ingredients of FDC has different therapeutic indication and is at variance from the concept and purpose of
+Ketoconazole FDC.
2. Combining antibiotics , antifungal, steroid in the present FDC is liable to be misuse and emergence of
resistance and adverse effects 3.Use of steroid in case of fungal infection might actually worsen the treatment as
it encourages fungal growth.No study is found supporting the combined use of an anti bacterial with an anti
fungal ingredient.
309 Allantoin+Dimethieone+Ure This FDC was earlier discussed by previous Committee on 22.8.2014 as under: S.O. 1013 (E)
a+Propylene+Glycerin+Liqu Firm did not turn up for presentation. The FDC is not rational as ingredients present in the FDC have antagonistic
id paraffin functions. Further, there are no supporting documents to prove that the FDC is rational for the proposed
indication. Hence, the committee did not recommend.
310 Acriflavine This FDC was earlier discussed by previous Committee on 22.8.2014 as under: S.O. 1014 (E)
+Thymol+Cetrimide Firm could not present any supporting data in respect of the rationality of the FDC. Moreover, the FDC is also
not approved anywhere in the world. Hence, the committee did not recommend.

There is no justification for addition of Thymol in this FDC (09.01.2016).

311 Betamethasone +Neomycin a, S.O. 1015 (E)

+Tolnaftate +Iodo Chloro Pharmacodynamically irrelevant-
Hydroxy Quinoline 1.Each ingredients of FDC has different therapeutic indication and is at variance from the concept and purpose of
+Cholorocresol FDC.
2. Combining antibiotics , antifungal, steroid ,iodochlorohydroxyquinone in the present FDC is liable to be
misuse and emergence of resistance and adverse effects 3.Use of steroid in case of fungal infection might actually
worsen the treatment as it encourages fungal growth.No study is found supporting the combined use of an anti
bacterial with an anti fungal ingredient.

312 clobetasol +Neomycin a, S.O. 1016 (E)

+Miconazole +Clotrimazole Pharmacodynamically irrelevant-
1.Each ingredients of FDC has different therapeutic indication and is at variance from the concept and purpose of
FDC.
2. Combining antibiotics , antifungal, steroid in the present FDC is liable to be misuse and emergence of
resistance and adverse effects 3.Use of steroid in case of fungal infection might actually worsen the treatment as
it encourages fungal growth.No study is found supporting the combined use of an anti bacterial with an anti
fungal ingredient.
313 Ketoconazole+Tea Tree a, S.O. 1017 (E)
oil+Allantion+zinc Pharmacodynamically irrelevant as the combination does not give any therapeutic benefit.
Oxide+Aloe Vera+Jojoba Use of zinc sulphate in Topical form is not scientifically proven (09.01.2016).
oil+Lavander oil+Soap
noodles
314 Clobetasol +Ofloxacin a, S.O. 1018 (E)
+Ornidazole +Terbinafine Pharmacodynamically irrelevant-
1.Each ingredients of FDC has different therapeutic indication and is at variance from the concept and purpose of
FDC.
2. Combining antibiotics , antifungal, steroid in the present FDC is liable to be misuse and emergence of
resistance and adverse effects 3.Use of steroid in case of fungal infection might actually worsen the treatment as
it encourages fungal growth.No study is found supporting the combined use of an anti bacterial with an anti
fungal ingredient.
315 Clobetasol +Neomycin a, S.O. 1019 (E)
+Miconazole +Zinc Pharmacodynamically irrelevant-
Sulphate 1.Each ingredients of FDC has different therapeutic indication and is at variance from the concept and purpose of
FDC.
2. Combining antibiotics , antifungal, steroid in the present FDC is liable to be misuse and emergence of
resistance and adverse effects 3.Use of steroid in case of fungal infection might actually worsen the treatment as
it encourages fungal growth.No study is found supporting the combined use of an anti bacterial with an anti
fungal ingredient.
316 Beclomethasone a, S.O. 1020 (E)
+Neomycin +Tolnaftate Pharmacodynamically irrelevant-
+Iodochlorhydroxyquinoline 1.Each ingredients of FDC has different therapeutic indication and is at variance from the concept and purpose of
+Chlorocresol FDC.
2. Combining antibiotics , antifungal, steroid, Iodochlorhydroxyquinoline in the present FDC is liable to be
misuse and emergence of resistance and adverse effects 3.Use of steroid in case of fungal infection might actually
worsen the treatment as it encourages fungal growth.No study is found supporting the combined use of an anti
bacterial with an anti fungal ingredient.

317 Betamethasone a, S.O. 1021 (E)

+Gentamycin +Zinc Pharmacodynamically irrelevant-
Sulphate +Clotrimazole 1.Each ingredients of FDC has different therapeutic indication and is at variance from the concept and purpose of
+Chlorocresol FDC.
2. Combining antibiotics , antifungal, steroid in the present FDC is liable to be misuse and emergence of
resistance and adverse effects 3.Use of steroid in case of fungal infection might actually worsen the treatment as
it encourages fungal growth.No study is found supporting the combined use of an anti bacterial with an anti
fungal ingredient.
318 Borax +Boric acid a, S.O. 1022 (E)
+Naphazoline +Menthol Pharmacodynamically irrelevant-
+Camphor + methyl 1. Therapeutic area not clear
hydroxy benzoate 2. Multiple ingredients with diverse pharmacological profile susceptible to pharmaceutically incompatibility
319 Bromhexine a, S.O. 1023 (E)
+Dextromethorphan Pharmacodynamically irrelevant-
1. Dextromethorphan: it decreases the cough impulse so expulsion of secretion would be hampered
2. Bromhexine:a mucolytic which increases mucus secretion should not given in combination with antihistaminic
with anti cholinergic properties, because due to anti cholinergic properties mucus secretions is dried up.

320 Dextromethophan a, S.O. 1024 (E)

+Chlopheniramine 1 Dosing schedule is incompatible.
+Bromhexine 2. Ingredients will aggravate the adverse effects of sedation and drowsiness and also will interefere with the
reflexes.
3.Centrally acting anti-tussive not to be combined with anti-histaminic drug.

321 Menthol +Anesthetic Ether a, S.O. 1025 (E)

Pharmacodynamically irrelevant-
1. No published literature supporting the use of combination.
322 Dextrometharphan a, S.O. 1026 (E)
+Chlopheniramine 1 Dosing schedule is incompatible.
+Ammonium Chloride 2. Ingredients will aggravate the adverse effects of sedation and drowsiness and also will interefere with the
+Sodium Citrate +Menthol reflexes.
3.Centrally acting anti-tussive not to be combined with anti-histaminic drug.

323 Ergotamine Tartrate a, S.O. 1027 (E)

+Belladona dry extract Pharmacodynamically irrelevant-
+Caffeine +Paracetamol 1. Belladona dry extract not indicated for migraine.
2. Dose of paracetamol is subtherapeutic.
324 Phenytoin +Phenobarbitone a, S.O. 1028 (E)
sodium Pharmacodynamically irrelevant.
1. Phenobarbital will decrease the level or effect of phenytoin by affecting hepatic enzyme CYP2C9/10
metabolism. Significant interaction possible.
2. Phenobarbital decreases levels of phenytoin by increasing metabolism.
3. Phenobarbital may occasionally not change or even increase (via competitive inhibition) phenytoin levels.

http://reference.medscape.com/drug-interactionchecker.
325 Gliclazide 40mg+Metformin a, S.O. 1029 (E)
400mg Sub-therapeutic dose of metformin.

326 Paracetamol + Ambroxol + a, S.O. 1030 (E)

Phenylephrine Pharmacodynamically irrelevant
+Chlorpheniramine 1. Dosing schedule is incompatible.
2. Ingredients will aggravate the adverse effects of sedation and drowsiness and also will interefere with the
reflexes.
3.Potential for drug-drug interaction.

327 Oflaxacin + Ornidazole a, S.O. 1031 (E)

suspension 1. Both ingredients of the FDC have different therapeutic indcations
2.Inappropriate use of ornidazole will lead to emergence of antibiotic resistance against quinalones.
3. Safety concerns in paediatric patients.

328 Albuterol + Etofylline + a, S.O. 1032 (E)

Bromhexine + Menthol 1. Etofylline is a narrow therapeutic indexed drug and requires close monitoring.
2.Patients may need only one ingredient and use of FDC may lead to misuse.

329 Albuterol + Bromhexine + a, S.O. 1033 (E)

Theophylline 1. Theophylline is a narrow therapeutic indexed drug and requires close monitoring.
2.Patients may need only one ingredient and use of FDC may lead to misuse.

330 Salbutamol + a, S.O. 1034 (E)

Hydroxyethyltheophylline 1. On the basis of current scientific understanding the FDC is pharmacodynamically irrelevant.
(Etofylline)+ Bromhexine 2. Use of Mucolytic alongwith anti-asthamatic drugs is liable to be misused as expectorant and exposing the
patients unnecessary to the drugs and their adverse effects.

331 Paracetamol +Phenylephrine a, S.O. 1035 (E)

+Levocetirizine +Sodium 1.Pharmacodynamically and phamacokinetically irrational FDC.
Citrate 2.Patients may need only one ingredient and use of FDC may lead to misuse.
3.Dosing shedule of the ingredients is incompatible.
4. Potential for drug-drug interaction.

332 Paracetamol a, S.O. 1036 (E)

+Propyphenazone +Caffeine Pharmacodynamically irrelevant-
1. Paracetamol dose is subtherapeutic.
2. Suceptibility of adverse drug reaction is very high.
3. Misuse potential.
333 Guaifenesin a, S.O. 1037 (E)
+Diphenhydramine Pharmacodynamically irrelevant-
+Bromhexine • Anticholinergic property of diphenhydramine will lead to drying up of secretions while mucolytics increase.
+Phenylephrine

334 Dried Alumnium Hydroxide a, S.O. 1038 (E)

Gel +Propantheline Bromide Pharmacodynamically irrelevant-
+Diazepam 1. No published literature supporting the FDC.
2. In present scenario Propanthaline has safety concerns.
3. Use of diazepam is irrational.

335 Bromhexine a, S.O. 1039 (E)

+Phenylephrine Pharmacodynamically irrelevant-
+Chlorpheniramine 1. Bromhexine :a mucolytic which increases mucus secretion should not given in combination with
+Paracetamol antihistaminic with anti cholinergic properties, because due to anti cholinergic properties mucus secretions is
dried up.
2. Chlorpheniramine :H1 antagonist are said to decrease rhinorrhea but the drying effect may do more harm
because of their tendency to induce somnolence
3. Potential misuse in FDC formualtion is likely to be hepatotoxic .

336 Beclomethasone a, S.O. 1040 (E)

+Clotrimazole+Gentamicin+ Pharmacodynamically irrelevant-
IodoChlorhydroxyquinoline 1.Each ingredients of FDC has different therapeutic indication and is at variance from the concept and purpose of
FDC.
2. Combining antibiotics , antifungal, steroid, Iodochlorhydroxyquinoline in the present FDC is liable to be
misuse and emergence of resistance and adverse effects 3.Use of steroid in case of fungal infection might actually
worsen the treatment as it encourages fungal growth.No study is found supporting the combined use of an anti
bacterial with an anti fungal ingredient.

337 Telmisartan + Metformin a, S.O. 1041 (E)

Pharmacodynamically irrelevant as no study supports this combination.

338 Ammonium a, S.O. 1042 (E)

Citrate+Vitamin B 12+Folic Pharmacodynamically irrelevant-
Acid+Zinc Sulphate 1. Therapeutic area not clear
2. ingredients susceptible to pharmaceutically incompatibility
339 levothyroxine pyridoxine+ a, S.O. 1043 (E)
nicotinamide Pharmacodynamically irrelevant-
1.Each ingredients of FDC has different therapeutic indication and is at variance from the concept and purpose of
FDC.

340 benfotiamine+ metformin This was discussed by previous Committee on 27.08.14 as under- S.O. 1044 (E)
The committee noted that the proposed FDC was also discussed earlier by NDAC on 06.10.2012.
There is not enough published data particularly in the human subjects regarding the efficacy. The data
presented by the firm(s) has been examined scientifically and firm has presented only animal study
data. The firm fails to present clinical data about synergistic effect of this FDC over other drugs present
in FDC. Moreover no scientific publication recommends this combination. This combination is also not
approved anywhere in the world. Hence the committee did not recommend for the manufacturing and
marketing of this FDC.
341 Thyroid +Thiamine + a, S.O. 1045 (E)
Riboflavin + Pyridoxine + No clinical studies found supporting the use of this combination
Calcium Pantothenate +
Tocopheryl Acetate
+Nicotinamide

342 Ascorbic Acid + Manadione a, Pharmacodynamically irrelevant- S.O. 1046 (E)

Sodium Bisulphate+ Rutin + 1. Therapeutic area not clear
Dibasic Calcium Phosphate 2. Multiple ingredients with diverse pharmacological profile.
+ Adrenochrome Mono
Semicarbazone

343 Phenylephrine a, S.O. 1047 (E)

+Chlorpheniramine 1.Pharmacodynamically and phamacokinetically irrational FDC.
+Paracetamol +Bromhexine 2.Patients may need only one ingredient and use of FDC may lead to misuse.
+Caffeine 3.Dosing shedule of the ingredients is incompatible.
4.Mucolytic increases mucus secretion and antihistaminic with anti cholinergic properties dry up secretions.
344 Clotrimazole a, S.O. 1048 (E)
+Beclomethasone Pharmacodynamically irrelevant-
+Lignocaine +Ofloxacin 1.Each ingredients of FDC has different therapeutic indication and is at variance from the concept and purpose of
+Acetic Acid + Sodium FDC.
Methyl Paraben +Propyl 2. Combining antibiotic , antifungal, steroid in the present FDC is liable to be misuse and emergence of
Paraben resistance and adverse effects.
3.Use of steroid in case of fungal infection might actually worsen the treatment as it encourages fungal growth.
NO study is found supporting the combined use of an antibacterial with an antifungal ingredient.
4.Lignocaine use in discharging ear is not required (07.01.2016).
 Details of 05 FDCs are as under:

345 Nimesulide + Levocetirizine S.O.1851 (E)

The FDC of Nimesulide + Levocetirizine was deliberated by SEC (Pulmonary) in its meeting held on DATED
24.09.2014. 08.06.2017
The committee examined and opined that the FDC is not rational as levocetirizine is anti-histaminic whereas
Nimesulide is an antipyretic analgesic and the combination is likely to be misused/overused in situations where
single drug is required. Further this FDC is not approved anywhere in the world. Hence the committee did not
recommended for its continued marketing in the country.

346 Ofloxacin + Ornidazole The FDC of Ofloxacin + Ornidazole injection was deliberated by NDAC (Antimicrobial, Antiparasitic, S.O.1852 (E)
injection Antifungal & Antiviral) in its meeting held on 28.02.2014 . The Committee noted the recommendation of the DATED
Parliament Standing Committee (PSC) and evaluated this drug in present scenario. The firm presented the data of 08.06.2017
phase III trial data. The committee noted that parenteral use of antibacterial in acute diarrhoea is not
recommended routinely. There is no specific advantage of giving Fluroquinolone and imidazole in parental form
as both can be given individually, if indicated. The FDC will not be rationale. Hence, the committee did not
recommend the FDC for continued marketing in India for the present approved indication of diarrhoea.

347 Gemifloxacin + Ambroxol The FDC of Gemifloxacin with Ambroxol was deliberated by SEC (Pulmonary) in its meeting held on 23-12- S.O.1853 (E)
2015. The proposal of continued marketing of Gemifloxacin + Ambroxol was deliberated in current scenario. DATED
The Committee opined that Ambroxol being a mucolytic agent does not have any added advantage in the 08.06.2017
antimicrobial activity. Therefore the Committee considered the FDC as irrational in current scenario and did not
recommend for its continued marketing.

348 Glucosamine + Ibuprofen The FDC of Glucosamine with Ibuprofen was deliberated by SEC (Analgesic & Rheumatology) in its meeting S.O.1854 (E)
held on 15.01.2016. DATED
The Committee reviewed the FDC for its continued marketing in the Country. Committee opined that 08.06.2017
glucosamine is required for long term use whereas Ibuprofen being NSAID is not recommended for long term.
Thus the FDC would lead to unnecessary overuse of NSAID leading to toxicity. Further the FDC is also not
approved Internationally. Hence the Committee did not recommend for its continued marketing.

349 Etodolac + Paracetamol The FDC of Etodolac + Paracetamol was deliberated by NDAC (Analgesics, Anesthetics & Rheumatology) in its S.O.1855 (E)
meeting held on 19.02.2014. The committee noted the recommendations of the PSC. The committee evaluated DATED
the safety and efficacy reports presented by the firm. The committee observed that the product shall not be 08.06.2017
prescribed more than 10 days as claimed by the firm. The committee opined that FDC is not required for short
term use as Paracetamol can be prescribed separately when required and can be tapered off early if need arises.
The committee recommended that the FDC is not rationale as present scenario.
 Annexure -2

REPORTABLE
IN THE SUPREME COURT OF INDIA
CIVIL APPELLATE JURISDICTION

CIVIL APPEAL NO. 22972 OF 2017

(ARISING OUT OF SLP (C) NO.7061 OF 2017

UNION OF INDIA AND ANR. …APPELLANTS

VERSUS

PFIZER LIMITED AND ORS. ...RESPONDENTS

WITH

CIVIL APPEAL NOS. 22973-22981 OF 2017

(ARISING OUT OF SLP (C) NO.10170-10178 OF 2017)

CIVIL APPEAL NOS. 22982-23404 OF 2017

(ARISING OUT OF SLP (C) NO.28960-29382 OF 2017)

TRANSFERRED CASE (C) NO.29 OF 2017

TRANSFERRED CASE (C) NO.30 OF 2017

TRANSFERRED CASE (C) NO.31 OF 2017

TRANSFERRED CASE (C) NO.32 OF 2017

TRANSFERRED CASE (C) NO.33 OF 2017

TRANSFERRED CASE (C) NO.34 OF 2017

Signature Not Verified

TRANSFERRED CASE (C) NO.35 OF 2017
Digitally signed by
VISHAL ANAND
Date: 2017.12.15
17:00:27 IST
Reason:
TRANSFERRED CASE (C) NO.36 OF 2017

1
 TRANSFERRED CASE (C) NO.38 OF 2017

TRANSFERRED CASE (C) NO.39 OF 2017

TRANSFERRED CASE (C) NO.40 OF 2017

TRANSFERRED CASE (C) NO.41 OF 2017

TRANSFERRED CASE (C) NO.42 OF 2017

TRANSFERRED CASE (C) NO.43 OF 2017

TRANSFERRED CASE (C) NO.44 OF 2017

TRANSFERRED CASE (C) NO.45 OF 2017

TRANSFER PETITION (C) NOS.1176-1182 OF 2017

TRANSFERRED CASE (C) NO.258 OF 2017

TRANSFERRED CASE (C) NO.259 OF 2017

TRANSFERRED CASE (C) NO.260 OF 2017

TRANSFERRED CASE (C) NO.261 OF 2017

TRANSFERRED CASE (C) NO.262 OF 2017

TRANSFERRED CASE (C) NO.263 OF 2017

TRANSFERRED CASE (C) NO.264 OF 2017

TRANSFERRED CASE (C) NO.265 OF 2017

TRANSFERRED CASE (C) NO.266 OF 2017

CIVIL APPEAL NOS. 23405-23472 OF 2017

(ARISING OUT OF SLP (C) NOS. 36044-36111 OF 2017
Diary No.28274 of 2017
2
 TRANSFERRED CASE (C) NOS. 308-317 OF 2017
(ARISING OUT OF T.P. (C) NOS.2108-2117 OF 2017)

JUDGMENT

R.F. Nariman, J.

1. Leave granted.

2. The present appeals and transfer petitions relate to the

interpretation of Section 26A of the Drugs and Cosmetics Act,

1940 (hereinafter referred to as “the Drugs Act”). By the

impugned judgment of the learned single Judge of the Delhi

High Court dated 1.12.2016, the learned single Judge has held

that the mandatory condition precedent for the exercise of the

power by the Central Government under Section 26A of the

Drugs Act is the prior consultation of the Drugs Technical

Advisory Board (DTAB) set up under Section 5 of the said Act.

It must be stated that the learned single Judge differed from

judgments of the Karnataka and Madras High Courts in this

regard, wherein two other learned single Judges of two other

3
High Courts have held that such consultation with the DTAB is

not mandatory before exercise of such power under Section

26A. Since we are concerned only with this narrow question

that has been decided by the learned single Judge of the Delhi

High Court, we are not going into any other contentions that

have been raised by learned counsel for the parties.

3. The issue regarding the prevalence of many Fixed Dose

Combinations (hereinafter referred to “FDCs”) that were

flooding the Indian market and had not been tested for efficacy

or safety was considered by the Parliamentary Standing

Committee on Health and Family Welfare in its 59 th Report in

May, 2012. The Standing Committee observed that some of

the State Licensing Authorities have issued manufacturing

licenses for a very large number of FDCs without prior

clearance from the Central Drugs Standard Control

Organization (CDSCO). Such FDCs can pose significant risks

to persons and need to be withdrawn immediately in that

human lives can be at risk. The Committee recommended that

a clear and transparent policy may be framed for approving

FDCs based on scientific principles, and that, at present,

4
Section 26A of the Drugs Act is adequate to deal with the

problem of FDCs not cleared by the CDSCO. Pursuant to the

aforesaid report, the Ministry of Health in October, 2012 issued

directions to States and Union Territories under Section 33P of

the Drugs Act not to grant licenses to FDCs falling under the

definition of “new drugs” and not approved by the Drug

Controller General of India (DCG(I)). The DCG(I), in turn, had

requested all States/Union Territories Drug Controllers to ask

concerned manufacturers in their respective States/Union

Territories to prove the safety and efficacy of such FDC licenses

issued prior to 1.10.2012, without due approval of the DCG(I),

within a period of 18 months, failing which such FDCs would be

considered for being prohibited, both qua manufacture and

marketing in the country. On 5.7.2013, the DCG(I) vide its

communication to the State Drug Controllers asked

manufacturers to make applications as per the procedure

prescribed within this 18 month period. We have been informed

that a large number of applications were received from the

manufacturers within the 18 month period for 2911 products,

which had to be subjected to examination.

5
4. With the approval of the Ministry of Health and Family

Welfare, the CDSCO constituted 10 different Committees for

examination of the said applications which were received on

3.2.2014. As the said Committees could examine only about

295 applications, on 16.9.2014, the Ministry of Health and

Family Welfare constituted a Committee under the

Chairmanship of Professor C.K. Kokate, Vice Chancellor of KLE

University, Belgaum, Karnataka for examining the safety and

efficacy as per the following terms of reference:

a. Those FDCs which are considered grossly

irrational/unsafe based on pharmacokinetic and
pharmacodynamic interaction, dosage
compatibilities of FDCs vis-a-vis that of single
ingredients present in the FDC and available
literature/evidence.
b. Those FDCs which the Committee may
consider necessary for further deliberation with any
of the 10 Expert Committees already constituted.
c. Those FDCs which are considered as safe
and effective based on pharmacokinetic and
pharmacodynamic interaction, dosage
compatibilities of FDCS vis-a-vis that of single
ingredients present in the FDC, available
literature/evidence, clinical experience and other
data available.
d. Those FDCs which may be considered as
rational, based on present data and knowledge
available. However, data in post market scenario is

6
 required to be generated within a period of 1 to 2
years to confirm the same.
e. All the FDCs falling, under category “b” above
would be referred to the respective Expert
Committee out of 10 Expert Committees already
constituted.
Composition of Expert Committee for examining the
safety & efficacy of Fixed Dose Combinations
(FDCs) is as under:

S.No. Name of Name & Qualificati Status in the

Expert Address of on Committee
Institutions
1 Prof. Vice-Chancellor, M. Pharm, Chairman
Chandrakant KLE University, Ph.D.
Kokate Belgaum,
Karnataka &
Ex-President of
Pharmacy
Council of India.
2 Dr. C.L. Kaul Former Director, B. Pharm, Member
NIPER, 432, Ph.D.
Mahatma
Society, Koth
Road, Pune-38.
3 Prof. Sanjay Deptt. of M. Pharm, Member
Singh Pharmaceutics, Ph.D.
IIT, BHU,
Varanasi.
4 Dr. C.D. Prof. & HOD MD, Member
Tripathi (Pharmacology), Pharamacol
Safdarjung ogy
Hospital, New

7
 Delhi.
5 Dr. Bikash Deptt. of MD, Member
Medhi Pharmacology, Pharmacolo
PGIMER, gy
Chandigarh.
6 Dr. Sanjeev Prof. (Medicine), MD, Member
Sinha AIIMS,New Delhi Medicine
7 Dr. R.K. Khar Former Dean & M. Pharm, Co-opted
Head, Jamia Ph.D. Member
Hamdard,
403,Lalleshwari
Vatika, GH-12,
Sector-21D,
Faridabad-1210
01.

A series of meetings were conducted by the

Committee (6 meetings corresponding to 11 days)
as well as by a sub-group of the Committee (2
meetings) for examination of these approx. 6320
applications.

5. The first assessment report of the aforesaid Committee

was submitted to the Ministry of Health and Family Welfare on

19.1.2015 and was presented before the Ministry on 4.3.2015,

wherein the Committee was requested to mention detailed

reasons against each FDC considered as “irrational” by the

Committee. The Committee did not discuss FDCs already

approved by the DCG(I) and FDCs which were licensed pre

8
21.9.1988 i.e. before the introduction of Schedule Y to the

Drugs Act. The Committee stated, “in case the Committee

made any comment with respect to the above inadvertently, it

shall be treated as not discussed.”

6. On 16.4.2015, a detailed report in this regard was

submitted by the Kokate Committee to the Ministry stating the

reasons for declaring FDCs as irrational. We have been

informed that for the FDCs which were considered as irrational

by the Committee, the Committee wrote to various

manufacturers/associations calling upon them to submit

material to establish the therapeutic justification/rationality of

the FDCs. Replies received from such associations were

examined by the Expert Committee and final recommendations

therein were given only on 10.2.2016. In category A, following

the final recommendations of the Expert Committee, the Central

Government has banned 344 FDCs. In category B, 944 FDCs

needed to be considered/deliberated upon further, which meant

that they would be referred to the respective Expert

Committees out of the 10 Expert Committees already

constituted for further examination. In category C, 1493 FDCs

9
have been declared “rational” and we are informed that

approvals have since been issued by the DCG(I) in respect of

these FDCs. In category D, 126 FDCs have to be considered

for further generation of data by the prospective applicants. It is

only after carrying out of this exercise, that by notifications

dated 10.3.2016 issued under Section 26A, the Central

Government banned manufacture and sale of 344 FDCs.

7. In March 2016, a large number of writ petitions were filed

in the Delhi High Court against the aforesaid notifications. The

impugned judgment then followed on 1.12.2016 disposing of

454 petitions, followed by an order dated 21.12.2016, in which

the Delhi High Court disposed of 51 further writ petitions in

terms of the judgment dated 1.12.2016.

8. Letters Patent Appeals were filed before the Delhi High

Court. Meanwhile, the Union of India filed transfer petitions in

this Court. This is how these matters have been heard by us in

civil appeals arising out of SLPs against the judgment of the

single Judge dated 1.12.2016 and in transfer cases in which the

10
LPAs pending before the Delhi High Court have been

transferred to us.

9. Ms. Pinky Anand, learned Additional Solicitor General,

took us through various provisions of the Drugs Act, and

emphasized that Section 26A does not expressly refer to the

DTAB. According to her, a large number of provisions of the

Drugs Act expressly refer to the DTAB in various contexts and,

therefore, it is not permissible for the Court to read a mandatory

requirement of consultation with the DTAB into Section 26A,

when such mandatory consultation is present in other

provisions, but is conspicuous by its absence in Section 26A.

She further went on to state that the provisions of Section 26A

are legislative in nature, and ultimately, once the Central

Government arrives at a satisfaction based on relevant

materials, judicial review of the Central Government decision

taken on the basis of Expert Committee reports is extremely

limited. She launched an all out attack against the single

Judge’s judgment and stated that the Madras and Karnataka

view, with which the Delhi High Court differed, is the correct

view in law. Shri Colin Gonsalves, learned senior counsel,

11
supported her arguments, and appeared in civil appeal arising

out of SLP(C) Nos.10170-10178 of 2017.

10. By way of reply, Shri C.S. Vaidyanathan, learned senior

counsel, argued that the impugned single Judge judgment was

based on an earlier Division Bench judgment in E. Merck

(India) Ltd. and another v. Union of India and another,

(2001) 90 DLT 60, which upheld the constitutional validity of

Section 26A on the ground that since the DTAB had to be

consulted before passing an order under Section 26A, the said

Section would pass constitutional muster. He also referred us

to this Court’s judgment in Systopic Laboratories (Pvt) Ltd. v.

Dr. Prem Gupta & Ors., 1994 Supp (1) SCC 160 in furtherance

of the same proposition. According to learned counsel, it is

clear on a reading of Section 5 of the Drugs Act, that it will

apply to both the Central Government and the State

Governments on all technical matters that arise out of the

administration of the Drugs Act. Since Section 26A deals only

with such technical matters, it is obvious that the DTAB’s advice

has to be taken in every such case as otherwise, if it were open

to the Central Government to pick and choose in which case

12
they would take such advice and which case they would not

take such advice, the provision itself would become arbitrary

and unreasonable. According to the learned senior counsel,

Section 5(5) of the Drugs Act is very important in that it is the

DTAB alone who may constitute sub-committees consisting of

persons who are not members of the DTAB, who may consider

particular matters, thereby making it clear that the DTAB alone

can induct experts who are outside Section 5 and not the

Central Government. He further referred to the Drugs and

Cosmetics Rules, 1945 (hereinafter referred to as the “Drugs

Rules”), in particular Rules 21, 68A, 122A, 122D and 122DA, to

buttress his submission that a detailed filtration process has to

be gone through before a drug can be manufactured and put on

the market and that the Central Government cannot ban such

drug without consulting the technical expert under the Drugs

Act namely, the DTAB, that is set up under Section 5. He also

argued that Sections 10A and 26A were introduced by way of

an amendment in 1982 and this being so, it is clear that it is

assumed by Parliament that Section 5 of the Drugs Act will be

13
read along with both of them so as to make the DTAB a

mandatory consultee before action is taken under Section 26A.

11. Shri Vashisht, learned senior counsel appearing for some

of the respondents, adverted to Section 5 and stated that it was

in two parts, the first being advice to the Central Government

on all technical matters arising out of the administration of the

Drugs Act and the second (and distinct part) being to carry out

other functions assigned to it by the Drugs Act. It is clear,

therefore, that in all matters which fall within the first part, the

advice of the Board would be mandatory before the Central

Government were to take action under Section 26A. He also

referred us to Section 7A of the Drugs Act and argued that

when the said Drugs Act expressly states that nothing in

Section 5 is to apply, it is expressly so stated and that,

therefore, the necessary inference would be that Section 5

would apply in all situations other than those covered by

Section 7A. He further argued that Section 26A does not have a

non obstante clause which puts out of harm’s way Section 5,

but only a “without prejudice” clause and that too restricted only

to Chapter IV, making it clear that Section 26A would have to be

14
read along with Section 5. According to him, therefore, there is

no reason to interfere with the judgment of the Delhi High

Court.

12. Dr. A.M. Singhvi, learned senior counsel, argued that on a

cursory look at the persons who constitute the DTAB under

Section 5, it is an extremely high ranking body which is the

technical expert set up by the statute and, therefore, the High

Court judgment is right in stating that in all cases arising under

Section 26A prior consultation with the DTAB is a must. He

argued, in the alternative, that on a purposive and harmonious

construction of the Drugs Act as a whole, a middle approach

could be that the Central Government may, in emergent

situations, not consult the DTAB, but in all other situations

should give reasons why the DTAB was not consulted,

otherwise the exercise under Section 26A would be found to be

constitutionally infirm. According to the learned senior counsel,

hearing is mandatory under the said Section and the High

Court’s reading in the requirement of hearing into the said

Section was absolutely correct. He also referred us to

judgments dealing with not only how hearing must be added

15
when it is absent, but to a judgment of this Court which stated

that conditional legislation, of which Section 26A is a clear

instance, would also require hearing the affected parties.

13. In answer to these submissions, the learned Additional

Solicitor General, in rejoinder, went through the 1982

amendment, which introduced Section 26A, and stated that

Sections 29 and 35 thereof make it clear that amendments

were made in certain Sections with reference to the DTAB

under Section 5 and that, therefore, the omission of any

reference to the DTAB in Section 26A is deliberate. She also

went on to state that Rule 66 of the Drugs Rules, which deals

with cancellation of individual licenses and which requires

compliance with natural justice, should be contrasted with

Section 26A of the Drugs Act which, according to her, is a

legislative power as opposed to an administrative power.

14. Having heard learned counsel for the parties, it is first

important to set out some of the provisions of the Drugs Act.

“5. The Drugs Technical Advisory Board.—

(1) The Central Government shall, as soon as may
be, constitute a Board (to be called the Drugs
Technical Advisory Board) to advise the Central
16
Government and the State Governments on
technical matters arising out of the administration of
this Act and to carry out the other functions
assigned to it by this Act.
(2) The Board shall consist of the following
members, namely:—
(i) the Director General of Health Services, ex
officio, who shall be Chairman;
(ii) the Drugs Controller, India, ex officio;
(iii) the Director of the Central Drugs Laboratory,
Calcutta, ex officio;
(iv) the Director of the Central Research Institute,
Kasauli, ex officio;
(v) the Director of the Indian Veterinary Research
Institute, Izatnagar, ex officio;
(vi) the President of the Medical Council of India, ex
officio;
(vii) the President of the Pharmacy Council of India,
ex officio;
(viii) the Director of the Central Drug Research
Institute, Lucknow, ex officio;
(ix) two persons to be nominated by the Central
Government from among persons who are in
charge of drugs control in the States;
(x) one person, to be elected by the Executive
Committee of the Pharmacy Council of India, from
among teachers in pharmacy or pharmaceutical
chemistry or pharmacology on the staff of an Indian
university or a college affiliated thereto;
(xi) one person, to be elected by the Executive
Committee of the Medical Council of India, from
among teachers in medicine or therapeutics on the
17
staff of an Indian university or a college affiliated
thereto;
(xii) one person to be nominated by the Central
Government from the pharmaceutical industry;
(xiii) one pharmacologist to be elected by the
Governing Body of the Indian Council of Medical
Research;
(xiv) one person to be elected by the Central
Council of the Indian Medical Association;
(xv) one person to be elected by the Council of the
Indian Pharmaceutical Association;
(xvi) two persons holding the appointment of
Government Analyst under this Act, to be nominated
by the Central Government.
(3) The nominated and elected members of the
Board shall hold office for three years, but shall be
eligible for re-nomination and re-election:
Provided that the person nominated or elected, as
the case may be, under clause (ix) or clause (x) or
clause (xi) or clause (xvi) of sub-section (2) shall
hold office for so long as he holds the appointment
of the office by virtue of which he was nominated or
elected to the Board.
(4) The Board may, subject to the previous approval
of the Central Government, make bye-laws fixing a
quorum and regulating its own procedure and the
conduct of all business to be transacted by it.
(5) The Board may constitute sub-committees and
may appoint to such sub-committees for such
periods, not exceeding three years, as it may
decide, or temporarily for the consideration of
particular matters, persons who are not members of
the Board.

18
(6) The functions of the Board may be exercised
notwithstanding any vacancy therein.
(7) The Central Government shall appoint a person
to be Secretary of the Board and shall provide the
Board with such clerical and other staff as the
Central Government considers necessary.
6. The Central Drugs Laboratory.—
(1) The Central Government shall, as soon as may
be, establish a Central Drugs Laboratory under the
control of a Director to be appointed by the Central
Government, to carry out the functions entrusted to
it by this Act or any rules made under this Chapter:
Provided that, if the Central Government so
prescribes, the functions of the Central Drugs
Laboratory in respect of any drug or class of drugs
or cosmetic or class of cosmetics shall be carried
out at the Central Research Institute, Kasauli, or at
any other prescribed Laboratory and the functions
of the Director of the Central Drugs Laboratory in
respect of such drug or class of drugs or such
cosmetic or class of cosmetics shall be exercised by
the Director of that Institute or of that other
Laboratory, as the case may be.
(2) the Central Government may, after consultation
with the Board, make rules prescribing—
(a) the functions of the Central Drugs Laboratory;
********
(d) the procedure for the submission of the said
Laboratory under Chapter IV or Chapter IVA of
samples of drugs or cosmetics for analysis or test,
the forms of Laboratory’s reports thereon and the
fees payable in respect of such reports;

19
(e) such other matters as may be necessary or
expedient to enable the said Laboratory to carry out
its functions;
(f) the matters necessary to be prescribed for the
purposes of the proviso to sub-section (1).
7. The Drugs Consultative Committee.—
(1) The Central Government may constitute an
advisory committee to be called “the Drugs
Consultative Committee” to advise the Central
Government, the State Governments and the Drugs
Technical Advisory Board on any matter tending to
secure uniformity throughout India in the
administration of this Act.
(2) The Drugs Consultative Committee shall consist
of two representatives of the Central Government to
be nominated by that Government and one
representative of each State Government to be
nominated by the State Government concerned.
(3) The Drugs Consultative Committee shall meet
when required to do so by the Central Government
and shall have power to regulate its own procedure.
7A. Sections 5 and 7 not to apply to Ayurvedic,
Siddha or Unani drugs.—
Nothing contained in sections 5 and 7 shall apply to
Ayurvedic, Siddha or Unani drugs.
8. Standards of quality.—
(1) For the purposes of this Chapter, the expression
“standard quality” means—
(a) in relation to a drug, that the drug complies with
the standard set out in the Second Schedule, and
(b) in relation to a cosmetic, that the cosmetic
compiles with such standard as may be prescribed.

20
(2) The Central Government, after consultation with
the Board and after giving by notification in the
Official Gazette not less than three months’ notice of
its intention so to do, may by a like notification add
to or otherwise amend the Second Schedule, for the
purposes of this Chapter, and thereupon the
Second Schedule shall be deemed to be amended
accordingly.
10. Prohibition of import of certain drugs or
cosmetics.—
From such date as may be fixed by the Central
Government by notification in the Official Gazette in
this behalf, no person shall import—
(a) any drug or cosmetic which is not of standard
quality;
(b) any misbranded drug or misbranded or spurious
cosmetic;
(bb) any adulterated or spurious drug;
(c) any drug or cosmetic for the import of which a
licence is prescribed, otherwise than under, and in
accordance with, such licence;
(d) any patent or proprietary medicine, unless there
is displayed in the prescribed manner on the label
or container thereof the true formula or list of active
ingredients contained in it together with the
quantities thereof;
(e) any drug which by means of any statement,
design or device accompanying it or by any other
means, purports or claims to cure or mitigate any
such disease or ailment, or to have any such other
effect, as may be prescribed;
(ee) any cosmetic containing any ingredient which
may render it unsafe or harmful for use under the
directions indicated or recommended;
21
(f) any drug or cosmetic the import of which is
prohibited by rule made under this Chapter:
Provided that nothing in this section shall apply to
the import, subject to prescribed conditions, of small
quantities of any drug for the purpose of
examination, test or analysis or for personal use:
Provided further that the Central Government may,
after consultation with the Board, by notification in
the Official Gazette, permit, subject to any
conditions specified in the notification, the import of
any drug or class of drugs not being of standard
quality.
12. Power of Central Government to make rules.
—
(1) The Central Government may, after consultation
with or on the recommendation of the Board and
after previous publication by notification in the
Official Gazette, make rules for the purpose of
giving effect to the provisions of this Chapter:
Provided that consultation with the Board may be
dispensed with if the Central Government is of
opinion that circumstances have arisen which
render it necessary to make rules without such
consultation, but in such a case the Board shall be
consulted within six months of the making of the
rules and the Central Government shall take into
consideration any suggestions which the Board may
make in relation to the amendment of the said rules.
(2) xxx xxx xxx
16. Standards of quality.—
(1) For the purposes of this Chapter, the expression
“standard quality” means—
(a) in relation to a drug, that the drug complies with
the standard set out in the Second Schedule, and
22
(b) in relation to a cosmetic, that the cosmetic
complies with such standard as may be prescribed.
(2) The Central Government, after consultation with
the Board and after giving by notification in the
Official Gazette not less than three months’ notice of
its intention so to do, may by a like notification add
to or otherwise amend the Second Schedule for the
purposes of this Chapter, and thereupon the
Second Schedule shall be deemed to be amended
accordingly.
18. Prohibition of manufacture and sale of
certain drugs and cosmetics.—
From such date as may be fixed by the State
Government by notification in the Official Gazette in
this behalf, no person shall himself or by any other
person on his behalf—
(a) manufacture for sale or for distribution, or sell, or
stock or exhibit or offer for sale, or distribute—
(i) any drug which is not of a standard quality, or is
misbranded, adulterated or spurious;
(ii) any cosmetic which is not of a standard quality
or is misbranded, adulterated or spurious;
(iii) any patent or proprietary medicine, unless there
is displayed in the prescribed manner on the label
or container thereof the true formula or list of active
ingredients contained in it together with the
quantities thereof;
(iv) any drug which by means of any statement,
design or device accompanying it or by any other
means, purports or claims to prevent, cure or
mitigate any such disease or ailment, or to have any
such other effect as may be prescribed;

23
(v) any cosmetic containing any ingredient which
may render it unsafe or harmful for use under the
directions indicated or recommended; and
(vi) any drug or cosmetic in contravention of any of
the provisions of this Chapter or any rule made
thereunder;
(b) sell, or stock or exhibit or offer for sale, or
distribute any drug or cosmetic which has been
imported or manufactured in contravention of any of
the provisions of this Act or any rule made
thereunder;
(c) manufacture for sale or for distribution, or sell, or
stock or exhibit or offer for sale, or distribute any
drug or cosmetic, except under, and in accordance
with the conditions of, a licence issued for such
purpose under this Chapter:
Provided that nothing in this section shall apply to
the manufacture, subject to prescribed conditions,
of small quantities of any drug for the purpose of
examination, test or analysis:
Provided further that the Central Government may,
after consultation with the Board, by notification in
the Official Gazette, permit, subject to any
conditions specified in the notification, the
manufacture for sale, or for distribution, sale,
stocking or exhibiting or offering for sale or
distribution of any drug or class of drugs not being
of standard quality.
26A. Powers of Central Government to prohibit
manufacture, etc., of drug and cosmetic in
public interest.—
Without prejudice to any other provision contained
in this Chapter, if the Central Government is
satisfied, that the use of any drug or cosmetic is
likely to involve any risk to human beings or animals
24
or that any drug does not have the therapeutic value
claimed or purported to be claimed for it or contains
ingredients and in such quantity for which there is
no therapeutic justification and that in the public
interest it is necessary or expedient so to do, then,
that Government may, by notification in the Official
Gazette, regulate, restrict or prohibit the
manufacture, sale or distribution of such drug or
cosmetic.
33. Power of Central Government to make rules.
—
(1) The Central Government may after consultation
with, or on the recommendation of, the Board and
after previous publication by notification in the
Official Gazette, make rules for the purpose of
giving effect to the provisions of this Chapter:
Provided that consultation with the Board may be
dispensed with if the Central Government is of
opinion that circumstances have arisen which
render it necessary to make rules without such
consultation, but in such a case the Board shall be
consulted within six months of the making of the
rules and the Central Government shall take into
consideration any suggestions which the Board may
make in relation to the amendment of the said rules.
(2) Without prejudice to the generality of the
foregoing power, such rules may—
(a) provide for the establishment of laboratories for
testing and analysing drugs or cosmetics;
(b) prescribe the qualifications and duties of
Government Analysts and the qualifications of
Inspectors;
(c) prescribe the methods of test or analysis to be
employed in determining whether a drug or
cosmetic is of standard quality;
25
(d) prescribe, in respect of biological and
organometallic compounds, the units or methods of
standardisation;
(dd) prescribe under clause (d) of section 17A the
colour or colours which a drug may bear or contain
for purposes of colouring;
(dda) prescribe under clause (d) of section 17E the
colour or colours which a cosmetic may bear or
contain for the purpose of colouring;
(e) prescribe the forms of licences for the
manufacture for sale or for distribution, for the sale
and for the distribution of drugs or any specified
drug or class of drugs or of cosmetics or any
specified cosmetic or class of cosmetics, the form of
application for such licences, the conditions subject
to which such licences may be issued, the authority
empowered to issue the same, the qualifications of
such authority and the fees payable therefor; and
provide for the cancellation or suspension of such
licences in any case where any provision of this
Chapter or the rules made thereunder is
contravened or any of the conditions subject to
which they are issued is not complied with;
(ee) prescribe the records, registers or other
documents to be kept and maintained under section
18B;
(eea) prescribe the fees for the inspection (for the
purposes of grant or renewal of licences) of
premises, wherein any drug or cosmetic is being or
is proposed to be manufactured;
(eeb) prescribe the manner in which copies are to
be certified under sub-section (2A) of section 22;
(f) specify the diseases or ailments which a drug
may not purport or claim to prevent, cure or mitigate

26
and such other effects which a drug may not purport
or claim to have;
(g) prescribe the conditions subject to which small
quantities of drugs may be manufactured for the
purpose of examination, test or analysis;
(h) require the date of manufacture and the date of
expiry of potency to be clearly or truly stated on the
label or container of any specified drug or class of
drugs, and prohibit the sale, stocking or exhibition
for sale, or distribution of the said drug or class of
drugs after the expiry of a specified period from the
date of manufacture or after the expiry of the date of
potency;
(i) prescribe the conditions to be observed in the
packing in bottles, packages, and other containers
of drugs or cosmetics, including the use of packing
material which comes into direct contact with the
drugs and prohibit the sale, stocking or exhibition for
sale, or distribution of drugs or cosmetics packed in
contravention of such conditions;
(j) regulate the mode of labelling packed drugs or
cosmetics, and prescribe the matters which shall or
shall not be included in such labels;
(k) prescribe the maximum proportion of any
poisonous substance which may be added or
contained in any drug, prohibit the manufacture,
sale or stocking or exhibition for sale, or distribution
of any drug in which that proportion is exceeded,
and specify substances which shall be deemed to
be poisonous for the purposes of this Chapter and
the rules made thereunder;
(l) require that the accepted scientific name of any
specified drug shall be displayed in the prescribed
manner on the label or wrapper of any patent or
proprietary medicine containing such drug;

27
[****]
(n) prescribe the powers and duties of Inspectors
and the qualifications of the authority to which such
Inspectors shall be subordinate and specify the
drugs or classes of drugs or cosmetics or classes of
cosmetics in relation to which and the conditions,
limitations or restrictions subject to which, such
powers and duties may be exercised or performed;
(o) prescribe the forms of report to be given by
Government Analysts, and the manner of
application for test or analysis under section 26 and
the fees payable therefor;
(p) specify the offences against this Chapter or any
rule made thereunder in relation to which an order
of confiscation may be made under section 31;
(q) provide for the exemption, conditionally or
otherwise, from all or any of the provisions of this
Chapter or the rules made thereunder, of any
specified drug or class of drugs or cosmetic or class
of cosmetics; and
(r) sum which may be specified by the Central
Government under section 32-B.
33EED. Power of Central Government to prohibit
manufacture, etc., of Ayurvedic, Siddha or Unani
drugs in public interest.—
Without prejudice to any other provision contained
in this Chapter, if the Central Government is
satisfied on the basis of any evidence or other
material available before it that the use of any
Ayurvedic, Siddha or Unani drug is likely to involve
any risk to human beings or animals or that any
such drug does not have the therapeutic value
claimed or purported to be claimed for it and that in
the public interest it is necessary or expedient so to
do then, that Government may, by notification in the
28
Official Gazette, prohibit the manufacture, sale or
distribution of such drug.
33N. Power of Central Government to make
rules.—
(1) The Central Government may, after consultation
with, or on the recommendation of, the Board and
after previous publication by notification in the
Official Gazette, make rules for the purpose of
giving effect to the provisions of this Chapter:
Provided that consultation with the Board may be
dispensed with if the Central Government is of
opinion that circumstances have arisen which
render it necessary to make rules without such
consultation, but in such a case, the Board shall be
consulted within six months of the making of the
rules and the Central Government shall take into
consideration any suggestions which the Board may
make in relation to the amendment of the said rules.
(2) Without prejudice to the generality of the
foregoing power, such rules may—
(a) provide for the establishment of laboratories for
testing and analysing Ayurvedic, Siddha or Unani
drugs;
(b) prescribe the qualification and duties of
Government Analysts and the qualifications of
Inspectors;
(c) prescribe the methods of test or analysis to be
employed in determining whether any Ayurvedic,
Siddha or Unani drug is labelled with the true list of
the ingredients which it is purported to contain;
(d) specify any substance as a poisonous
substance;
(e) prescribe the forms of licences for the
manufacture for sale of Ayurvedic, Siddha or Unani
29
 drugs, and for sale of processed Ayurvedic, Siddha
or Unani drugs, the form of application for such
licences, the conditions subject to which such
licences may be issued, the authority empowered to
issue the same and the fees payable therefor; and
provide for the cancellation or suspension of such
licences in any case where any provision of this
Chapter or rules made thereunder is contravened or
any of the conditions subject to which they are
issued is not complied with;
(f) prescribe the conditions to be observed in the
packing of Ayurvedic, Siddha and Unani drugs
including the use of packing material which comes
into direct contact with the drugs, regulate the mode
of labelling packed drugs and prescribe the matters
which shall or shall not be included in such labels;
(g) prescribe the conditions subject to which small
quantities of Ayurvedic, Siddha or Unani drugs may
be manufactured for the purpose of examination,
test or analysis;
(gg) prescribe under clause (d) of section 33EE the
colour or colours which an Ayurvedic, Siddha or
Unani drug may bear or contain for purposes of
colouring;
(gga) prescribe the standards for Ayurvedic, Siddha
or Unani drugs under section 33EEB;
(ggb) prescribe the records, registers or other
documents to be kept and maintained under section
33 KB; and
(h) any other matter which is to be or may be
prescribed under this Chapter.”

15. Having heard learned counsel for the parties, it is clear

that Section 26A has been introduced by an amendment in

30
1982. A bare reading of this provision would show, firstly, that it

is without prejudice to any other provision contained in this

Chapter (meaning thereby Chapter IV). This expression only

means that apart from the Central Government’s other powers

contained in Chapter IV, Section 26A is an additional power

which must be governed by its own terms. Under Section 26A,

the Central Government must be “satisfied” that any drug or

cosmetic is likely to involve (i) any risk to human beings or

families; or (ii) that any drug does not have the therapeutic

value claimed or purported to be claimed for it; or (iii) contains

ingredients in such quantity for which there is no therapeutic

justification. Obviously, the Central Government has to apply its

mind to any or all of these three factors which has to be based

upon its “satisfaction” as to the existence of any or all of these

factors. The power exercised under Section 26A must further be

exercised only if it is found necessary or expedient to do so in

public interest. When the power is so exercised, it may

regulate, restrict or prohibit manufacture, sale or distribution of

any drug or cosmetic.

31
16. Undoubtedly, Section 26A has to be read with the rest of

the Drugs Act. So read, it is clear that unlike Section 6(2),

Section 8(2), second proviso to Section 10, proviso to Section

12(1), Section 16(2), proviso to Section 18(2), Section 33 and

Section 33N, there is no explicit requirement to consult the

DTAB set up under Section 5 of the Drugs Act. The question is

did the Parliament do so deliberately or is it something that the

Court should read into the provision?

17. As has been stated hereinabove, Section 26A was

brought in by an amendment in 1982. The amendment

specifically made changes in Sections 33 and 33N in which it

added the words “on the recommendation of the Board”. From

this, it is clear that Parliament in the very Amendment Act which

introduced Section 26A made certain changes which involved

the DTAB under Section 5 of the said Act. It is clear that the

additional power that is given to the Central Government under

Section 26A does not refer to and, therefore, mandate any

previous consultation with the DTAB. On the contrary, the

Central Government may be “satisfied” on any relevant material

that a drug is likely to involve any risk to human beings etc. as a

32
result of which it is necessary in public interest to regulate,

restrict or prohibit manufacture, sale or distribution thereof. So

long as the Central Government’s satisfaction can be said to be

based on relevant material, it is not possible to say that not

having consulted the DTAB, the power exercised under the said

Section would be non est. Take the case of an FDC that is

banned in 50 countries of the world owing to the fact that the

said FDC involved significant risk to human beings. Assuming

that the Central Government is satisfied based on this fact

alone, which in turn is based on expert committee reports in

various nations which pointed out the deleterious effects of the

said drug, can it be said that without consulting the DTAB set up

under Section 5, the exercise of the power under Section 26A

to prohibit the manufacture or sale or distribution of a drug that

is banned in 50 countries would be bad only because the DTAB

has not been consulted? The obvious answer is no inasmuch

as the Central Government’s satisfaction is based upon

relevant material, namely, the fact that 50 nations have banned

the aforesaid drug, which in turn is based on expert committee

reports taken in each of those nations. Take another example.

33
Suppose the Central Government were to ban an FDC on the

ground that, in the recent past, it has been apprised of the fact

that the FDCs taken over a short period of time would lead to

loss of life, which has come to the notice of the Central

Government through reports from various district authorities, in

let us say, a majority of districts in which the said FDC has been

consumed. Could not the Central Government then base its

ban order on material collected from district authorities which

state that this particular drug leads to human mortality and

ought, therefore, to be prohibited? The obvious answer again is

yes for the reason that the Central Government has been

satisfied on relevant material that it is necessary in public

interest to ban such drug. Examples of this nature can be

multiplied to show that the width of the power granted under

Section 26A cannot be cut down by artificially cutting down the

language of Section 26A.

18. We were referred to a judgment of this Court in Systopic

Laboratories (supra) at 169. Paragraph 19 of the said

judgment reads as follows:-

34
 “19. Having considered the submissions made by
the learned counsel for the petitioners and the
learned Additional Solicitor General in this regard,
we must express our inability to make an
assessment about the relative merits of the various
studies and reports which have been placed before
us. Such an evaluation is required to be done by the
Central Government while exercising its powers
under Section 26-A of the Act on the basis of expert
advice and the Act makes provision for obtaining
such advice through the Board and the DCC.”

19. It is clear that a stray sentence in a judgment without a

focused argument cannot be considered as the ratio of such a

judgment. Also, on a careful reading of the second sentence in

paragraph 19, it is clear that all that is stated by this Court is

that, while exercising its power under Section 26A of the Drugs

Act, the basis of the Central Government’s decision must be

“expert advice”. The sentence then goes on to add that the

Drugs Act makes provision for obtaining such advice through

the Board and the DCC. According to us, there was no focused

argument on whether such advice is or is not mandatory before

powers under Section 26A of the Drugs Act can be exercised,

and merely reading a stray sentence in this judgment does not

lead to such a conclusion. Equally, the single Judge’s reliance

upon a Division Bench judgment contained in E. Merck (supra),

35
where, in holding Section 26A to be constitutional, the Court

stated:

“Before the Government records its satisfaction to

prohibit the manufacture, sale, distribution etc. of a
particular drug, opinion of the DTAB and/or Drugs
Consultative Committee is obtained.”
This is an equally stray sentence and what has been

stated with respect to Systopic Laboratories (supra), applies

equally to this sentence.

20. We have now to consider certain other arguments made

on behalf of the respondents. One argument was that Section

5 is in two parts and that the first part necessarily applies to all

technical matters that arise out of the administration of the

Drugs Act, and that, therefore, the Central Government is

bound to take the advice of the DTAB in all such matters. We

must first advert to the fact that the DTAB is only an advisory

body. No doubt, it would be desirable for the Central

Government to take its advice on technical matters arising out

of the administration of the Drugs Act, but this does not lead to

the conclusion that if such advice is not taken power under

Section 26A cannot be exercised. Indeed, the Central

36
Government’s satisfaction may be based on a number of

factors, one of which may be advice tendered to it by the DTAB

under Section 5. There is no warrant to read Section 26A to

constrict the wide powers granted to the Central Government

by a so-called harmonious construction of the statute. Another

argument made is that Section 5 makes it clear that the DTAB

alone can constitute sub-committees which may have persons

who are not members of the Board on them. We are afraid that

this again does not lead us very far. It is clear that the reason

for Section 5(5) is completely different. Sub-committees may

be appointed for such periods not exceeding three years or

temporarily for the consideration of particular matters. Such

sub-committees may be set up in the wisdom of the DTAB for

short periods of time or temporarily to consider certain matters

and make reports which the DTAB may then utilize. This is a

power of the DTAB which can be exercised when the DTAB

deems it desirable. From this power, it cannot be inferred, as a

matter of logic, that since Section 5(5) permits persons who are

not members of the board to sit on sub-committees, the Central

Government may not, under Section 26A, refer to any persons

37
other than those who are board members. This argument,

therefore, is also rejected.

21. Yet another argument has been made that since Section

10A and 26A were brought in together by an Amendment Act in

1982, it must, therefore, somehow be assumed that the

Amendment Act necessarily included a mandatory consultation

with the DTAB set up under Section 5. We have already

pointed out how the very amendment Act of 1982 also

amended Sections 33 and 33N by referring to the DTAB and

that, therefore, it is obvious that the omission of any reference

to the DTAB under Sections 10A and 26A cannot but be said to

be deliberate. This argument also need not detain us further.

22. A negative argument was made stating that Section 7A of

the Drugs Act makes it clear that Section 5 will not apply to

Ayurvedic, Siddha or Unani drugs and that, therefore, it will

apply to all other drugs. The reason for Section 7A is again

something very different from what has been argued. It must

first be pointed out that under Chapter IVA, which is a separate

Chapter introduced by Act 13 of 1964, Ayurvedic, Siddha and

38
Unani drugs are completely separately dealt with. Indeed,

Section 33A, which must be read with Section 7A, expressly

provides that save as provided in this Drugs Act, nothing

contained in this Chapter, i.e. Chapter IV, shall apply to

Ayurvedic, Siddha or Unani drugs. Chapter IVA consists of a

separate and distinct drill to be followed in the case of

Ayurvedic, Siddha and Unani drugs. Under Section 33C, there

is a separate technical advisory board for Ayurvedic and Unani

drugs and a separate consultative committee for Ayurvedic,

Siddha and Unani drugs (see Section 33D). When Section 7A

says that nothing in section 5 shall apply to Ayurvedic, Siddha

or Unani drugs, all that it affirms is that the DTAB set up under

Section 5 will apply to all drugs except Ayurvedic, Siddha or

Unani medicines. The Latin maxim “expressio unius est

exclusio alterius” cannot apply, as has been held in State of

Karnataka v Union of India & Ors., (1977) 4 SCC 608 at 662,

making it clear that the said maxim should be very carefully

applied and when misapplied would turn out to be a “dangerous

master” as opposed to a “useful servant”. This has also been

held in Assistant Collector of Central Excise, Calcutta

39
Division v. National Tobacco Co. of India Ltd., (1972) 2 SCC

560 at 575 as follows:

“The High Court's view was based on an application

of the rule of construction that where a mode of
performing a duty is laid down by law it must be
performed in that mode or not at all. This rule flows
from the maxim: “Expressio unius ast exclusio
alterius”. But, as was pointed out by Wills, J.,
in Colguoboun v. Brooks [(1888) 21 QBD 52, 62]
this maxim “is often a valuable servant, but a
dangerous master….”. The rule is subservient to the
basic principle that Courts must endeavour to
ascertain the legislative intent and purpose, and
then adopt a rule of construction which effectuates
rather than one that may defeat these. “

This argument, therefore, also need not detain us.

23. It was also argued that Section 26A had no non obstante

clause to keep Section 5 out of harm’s way. On our

construction of Section 26A, it is clear that no such non

obstante clause was necessary in that the width of the

expression “is satisfied” contained in Section 26A cannot be cut

down by reference to Section 5. As has been stated by us

hereinabove, the expression “without prejudice” makes it clear

that Section 26A is an additional power given to the Central

Government which must be exercised on its own terms.

40
24. An argument was made that unless the provisions of

Section 5 requiring consultation with the DTAB are read into

Section 26A, the said Section would be arbitrary. In our

opinion, there are sufficient indicators in the Section to eschew

any ground of arbitrariness. The power can only be exercised

based on satisfaction of material that is relevant to form an

opinion that the drug in question falls within any of the three

categories outlined by the Section and that, further, it is

necessary or expedient to either regulate, restrict or prohibit

manufacture, sale or distribution of the said drug in public

interest. Indeed, this is made explicit in Section 33 EED of the

Drugs Act, wherein a similar power is given to the Central

Government qua Ayurvedic, Siddha or Unani drugs, where the

Section states:

“… the Central Government is satisfied on the basis

of any evidence or other material available before it
that …”

25. If the power under Section 26A is exercised on the basis

of irrelevant material or on the basis of no material, the

satisfaction itself that is contemplated by Section 26A would not

41
be there and the exercise of the power would be struck down

on this ground. Further, it is argued that the provision may be

read down to make it constitutionally valid, but in so doing,

words cannot be added as a matter of constitutional doctrine.

26. In Cellular Operators Association of India and others

v. Telecom Regulatory Authority of India and others, (2016)

7 SCC 703 at 740-741, this Court held as under:

“50. But it was said that the aforesaid Regulation

should be read down to mean that it would apply
only when the fault is that of the service provider.
We are afraid that such a course is not open to us in
law, for it is well settled that the doctrine of reading
down would apply only when general words used in
a statute or regulation can be confined in a
particular manner so as not to infringe a
constitutional right. This was best exemplified in one
of the earliest judgments dealing with the doctrine of
reading down, namely, the judgment of the Federal
Court in Hindu Women’s Rights to Property Act,
1937, In re [Hindu Women’s Rights to Property Act,
1937, In re, AIR 1941 FC 72]. In that judgment, the
word “property” in Section 3 of the Hindu Women’s
Rights to Property Act was read down so as not to
include agricultural land, which would be outside the
Central Legislature’s powers under the Government
of India Act, 1935. This is done because it is
presumed that the legislature did not intend to
transgress constitutional limitations. While so
reading down the word “property”, the Federal Court
held:

42
 “… If the restriction of the general words
to purposes within the power of the
legislature would be to leave an Act with
nothing or next to nothing in it, or an Act
different in kind, and not merely in
degree, from an Act in which the general
words were given the wider meaning,
then it is plain that the Act as a whole
must be held invalid, because in such
circumstances it is impossible to assert
with any confidence that the legislature
intended the general words which it has
used to be construed only in the
narrower sense: Owners of SS Kalibia v.
Wilson [(1910) 11 CLR 689 (Aust)],
Vacuum Oil Co. Pty. Ltd. v. Queensland
[(1934) 51 CLR 677 (Aust)], R. v.
Commonwealth Court of Conciliation
and Arbitration, ex p Whybrow & Co.
[(1910) 11 CLR 1 (Aust)] and British
Imperial Oil Co. Ltd. v. Federal Commr.
of Taxation [(1925) 35 CLR 422 (Aust)].”
51. This judgment was followed by a Constitution
Bench of this Court in DTC v. Mazdoor Congress
[1991 Supp (1) SCC 600 : 1991 SCC (L&S) 1213].
In that case, a question arose as to whether a
particular regulation which conferred power on an
authority to terminate the services of a permanent
and confirmed employee by issuing a notice
terminating his services, or by making payment in
lieu of such notice without assigning any reasons
and without any opportunity of hearing to the
employee, could be said to be violative of the
appellants’ fundamental rights. Four of the learned
Judges who heard the case, the Chief Justice alone
dissenting on this aspect, decided that the
regulation cannot be read down, and must,
therefore, be held to be unconstitutional. In the lead

43
judgment on this aspect by Sawant, J., this Court
stated: (SCC pp. 728-29, para 255)
“255. It is thus clear that the doctrine of
reading down or of recasting the statute
can be applied in limited situations. It is
essentially used, firstly, for saving a
statute from being struck down on
account of its unconstitutionality. It is an
extension of the principle that when two
interpretations are possible — one
rendering it constitutional and the other
making it unconstitutional, the former
should be preferred. The
unconstitutionality may spring from
either the incompetence of the
legislature to enact the statute or from
its violation of any of the provisions of
the Constitution. The second situation
which summons its aid is where the
provisions of the statute are vague and
ambiguous and it is possible to gather
the intentions of the legislature from the
object of the statute, the context in
which the provision occurs and the
purpose for which it is made. However,
when the provision is cast in a definite
and unambiguous language and its
intention is clear, it is not permissible
either to mend or bend it even if such
recasting is in accord with good reason
and conscience. In such circumstances,
it is not possible for the court to remake
the statute. Its only duty is to strike it
down and leave it to the legislature if it
so desires, to amend it. What is further,
if the remaking of the statute by the
courts is to lead to its distortion that
course is to be scrupulously avoided.
One of the situations further where the
44
 doctrine can never be called into play is
where the statute requires extensive
additions and deletions. Not only it is no
part of the court’s duty to undertake
such exercise, but it is beyond its
jurisdiction to do so.”
(emphasis supplied)
52. Applying the aforesaid test to the impugned
Regulation, it is clear that the language of the
Regulation is definite and unambiguous — every
service provider has to credit the account of the
calling consumer by one rupee for every single call
drop which occurs within its network. The
Explanatory Memorandum to the aforesaid
Regulation further makes it clear, in Para 19 thereof,
that the Authority has come to the conclusion that
call drops are instances of deficiency in service
delivery on the part of the service provider. It is thus
unambiguously clear that the impugned Regulation
is based on the fact that the service provider is
alone at fault and must pay for that fault. In these
circumstances, to read a proviso into the Regulation
that it will not apply to consumers who are at fault
themselves is not to restrict general words to a
particular meaning, but to add something to the
provision which does not exist, which would be
nothing short of the court itself legislating. For this
reason, it is not possible to accept the learned
Attorney General’s contention that the impugned
Regulation be read down in the manner suggested
by him.”

27. Also, as a matter of statutory interpretation, words can

only be added if the literal interpretation of the Section leads to

an absurd result. As has been stated by us, the construction of

45
Section 26A on a literal reading thereof does not lead to any

such result. Dr. Singhvi’s argument to read in words to save

Section 26A must, therefore, be rejected.

28. We may also mention that the Madras High Court in its

judgment in Macleods Pharmaceuticals Limited v. Union of

India & Ors., Writ Petition Nos.21933 and 25442 of 2011,

specifically held as under:

“38. Thus, the Act gives in every Chapter, an

indication of the functions to be exercised by the
DTAB. In other words, the territory within which the
DTAB is to operate and exercise its functions, is
clearly demarcated in various provisions of the Act
such as 5(1), 6(2), 7(1), 8(2), second proviso to
Section 10, 12(1) and 33(1). But Section 26-A is
completely silent about any consultation with DTAB.
It is so even with Section 26-B.
39. While the advisory role of DTAB is indicated in
broad and general terms in Section 5(1), it is
indicated in specific terms in Sections 6(2), 7(1),
8(2), second proviso to Section 10, 12(1) and 33(1).
Therefore, the absence of any reference to such
requirement of consultation in Section 26-A
assumes great significance. It is a well settled
principle of interpretation of statutes that the Courts
are not expected to supply the omission. The
Parliament had consciously incorporated the
expressions “after consultation with the Board” or
“on the recommendation of the Board”, in certain
provisions of the Act such as Sections 5(1), 6(2),
7(1), 8(2), second proviso to Section 10, 12(1) and
33(1). But it has deliberately omitted to include any
46
 of those expressions while inserting Sections 26-A
and 26-B. It is a case of casus omisus. Therefore,
the argument that the Central Government ought to
have taken the consultation of the DTAB before
issuing the ban order, can hold good only if I can
supply into Section 26-A, what was deliberately left
out by the Parliament. This cannot be done by me
and hence the first contention has to be rejected.”

29. To similar effect is the judgment of a single Judge of the

Karnataka High Court in Lundbeck India Pvt. Ltd. v Union of

India, (2014) 5 Kant LJ 440.

30. We approve of these two judgments as having laid down

the correct law on the construction of Section 26A of the Drugs

Act.

31. Though arguments have been made as to whether

Section 26A is legislative in nature and therefore excludes

natural justice, we do not propose to go into the same

inasmuch as since the learned single Judge’s judgment is being

set aside on one point and one point alone. In this view of the

matter, we are of the opinion that the impugned judgment dated

1.12.2016 deserves to be set aside.

47
32. On the facts of these cases, a suggested course of action

was stated by learned counsel appearing on behalf of the

petitioners/appellants. This course is that instead of now

remitting the matter back to the Delhi High Court for an

adjudication on the other points raised in the writ petitions, the

case of 344 FDCs that have been banned, plus another 5 FDCs

that have been banned, which comes to 349 FDCs, (barring 15

FDCs that are pre 1988 and 17 FDCs which have DCG(I)

approval) pursuant to the Kokate Committee report, by

notifications of the Central Government under Section 26A of

the Drugs Act, should be sent to the DTAB, constituted under

Section 5 of the Drugs Act, so that it can examine each of these

cases and ultimately send a report to the Central Government.

We reiterate that only on the peculiar facts of these cases, we

think that such a course commends itself to us, which would

obviate further litigation and finally set at rest all other

contentions raised by the petitioners. We say so because we

find that the Kokate Committee did deliberate on the 344 FDCs

plus 5 FDCs and did come to a conclusion that the aforesaid

FDCs be banned, but we are not clear as to what exactly the

48
reasons for such conclusions are, and whether it was

necessary in the public interest to take the extreme step of

prohibiting such FDCs, instead of restricting or regulating their

manufacture and supply. In order that an analysis be made in

greater depth, we, therefore, feel that these cases should go to

the DTAB and/or a Sub-Committee formed by the DTAB for the

purpose of having a relook into these cases. It is important,

however, that the DTAB/Sub-Committee appointed for this

purpose will not only hear the petitioners/appellants before us,

but that they also hear submissions from the All India Drugs

Action Network. The DTAB/Sub-Committee set up for this

purpose will deliberate on the parameters set out in Section

26A of the Drugs Act, as follows.

33. First and foremost in each case, the

DTAB/Sub-Committee appointed by it must satisfy itself that the

use of the Fixed Dose Combinations (FDC) in question is likely

to involve any one of the aforesaid three things:

(a) that they are likely to involve any risk to human beings or

animals; or

49
(b) that the said FDCs do not have the therapeutic value

claimed or purported to be claimed for them; or

(c) that such FDCs contain ingredients and in such quantity for

which there is no therapeutic justification.

34. The DTAB/Sub-Committee must also apply its mind as to

whether it is then necessary or expedient, in the larger public

interest, to regulate, restrict or prohibit the manufacture, sale or

distribution of such FDCs. In short, the DTAB/Sub-Committee

must clearly indicate in its report:

(1) as to why, according to it, any one of the three factors

indicated above is attracted;

(2) post such satisfaction, that in the larger public interest, it is

necessary or expedient to (i) regulate, (ii) restrict, or (iii) prohibit

the manufacture, sale or distribution of such FDCs.

35. The DTAB/Sub-Committee must also indicate in its report

as to why, in case it prohibits a particular FDC, restriction or

regulation is not sufficient to control the manufacture and use of

the FDC. We request the DTAB/Sub-Committee to be set up

for this purpose to afford the necessary hearing to all

50
concerned, and thereafter submit a consolidated report, insofar

as these FDCs are concerned, to the Central Government

within a period of six months from the date on which this

judgment is received by the DTAB. We may also indicate that

the Central Government, thereafter, must have due regard to

the report of the DTAB and to any other relevant information,

and ultimately apply its mind to the parameters contained in

Section 26A of the Drugs Act and, accordingly, either maintain

the notifications already issued, or modify/substitute them or

withdraw them.

36. With these directions given on the peculiar facts and

circumstances of these cases, the appeals are disposed of.

37. Insofar as the drugs that have been banned and which

were manufactured pre 21st September, 1988, a list of 15 such

drugs has been given to us by Mr. Kapil Sibal, learned senior

counsel for the respondents. We set aside the Central

Government notifications banning them as these cases were

never meant to be referred to the Kokate Committee. It will be

open, however, for the Central Government, if it so chooses, de

51
novo, to carry out an inquiry as to whether such drugs should

be the subject matter of a notification under Section 26A of the

Drugs Act.

38. Insofar as the list of 17 cases handed over by Shri Sibal,

in which DCG(I) approvals have allegedly been granted, we are

of the view that since the Parliamentary Standing Committee

itself refers to DCG(I) approvals and the manner in which they

were granted, we do not accede to Mr. Sibal's request that

these 17 cases be kept outside the purview of the fresh look

that has to be given by the DTAB/Sub-Committee in these

cases.

39. Insofar as the status quo, obtaining as on today, is

concerned, that will continue in all cases (including the 5 FDCs

which are not the subject matter of stay orders already made)

until the Central Government issues fresh notifications in this

behalf.

MADRAS CASES (TRANSFERRED CASES)

T.C.(C)Nos. 308-317_of 2017 @ T.P.(C)Nos.2108-2117 of 2017

52
40. Mr. Gopal Subramanium, learned senior counsel

appearing on behalf of the original petitioners in these cases,

stated that these cases have been transferred to this Court

from the Madras High Court. A Section 33 ban, which was

imposed on 294 FDCs in these cases, has been stayed by the

Madras High Court, and the very exercise that we have

proposed in the Delhi cases has apparently been carried out in

this group of cases. A report of the expert committee of the

DTAB to review the rationality and safety of 294 FDCs is taken

on record. The report indicates that 42 FDCs reportedly were

repeated or duplicate; 44 were already prohibited for

manufacture in the country; 83 were considered rational; 56

were considered not rational; 49 required further generation of

data; 17 were considered inadequate so far as rationality, safety

and efficacy is concerned; and 3 other cases were sent for

further examination by an expert committee constituted by the

Ministry of Health and Family Welfare. The DTAB after review

of the report and deliberations recommended that the FDC

Ofloxacin and Prednisolone at serial number 75 under the

category of GI in Annexure C does not appear to be rational

53
and should be re-examined. The list of the drugs mentioned in

Annexure D are required to be prohibited/withdrawn from the

market as these are not rational. Considering that an expert

body has already deliberated upon and decided these cases,

we accept the report, and accordingly dispose of these petitions

in accordance therewith.

……………………….J.
(R.F. Nariman)

……………………….J.
(Sanjay Kishan Kaul)
New Delhi;
December 15, 2017.

54
 ANNEXURE 3

(To be published in part II, Section 3, Sub-section (i) of the Gazette of India,
Extraordinary, dated the…..)
Government of India
Ministry of Health and Family Welfare
(Department of Health and Family Welfare)
New Delhi, the , 2017

Notification

G.S.R._______ (E).-The following draft of certain rules which the Central

Government proposes to make in exercise of the power conferred by sections 12
and 33 of the Drugs and Cosmetic Act, 1940 (23 of 1940) and in consultation after
publication with the Drugs Technical Advisory Board is hereby published for
information of all persons likely to be affected thereby and notice is hereby given that
the said draft rules shall be taken into consideration or after the expiry of a period of
thirty days from the date on which the copies of the Gazette of India these draft rules
are made available to public.

Objections and suggestions which may be received from any person within
the period specified above will be considered by the Central Government.

Objections and suggestions, if any, may be addressed to the Under Secretary

(Drugs), Ministry of Health and Family Welfare, Government of India, Room No. 414
A, D Wing, Nirman Bhawan, New Delhi – 110011 or sent on email drugsdiv-
[email protected].

Draft Rules

1. (1) These rules may be called Drugs and Cosmetics (________Amendment)

Rules, 2017.

(2) They shall come into force after their final publication in the Official
Gazette.

2. In the Drugs and Cosmetics Rules, 1945, in rule 96 sub-rule (1),-

 (a) in clause (ii) at the end for the words “Metric system” the words “Metric
system; and Ex-factory price or import price as the case may be, in figures.”
shall be substituted;

(b) at the end of clause (ii) so amended the following Explanation shall be
inserted, namely,-

“Explanation.- For the purpose of these rules,-

(i) “Ex-factory price” means price on which the goods and service tax is payable
under the Central Goods and Service Tax Act, 2017 (12 of 2017) by the first
buyer.

(ii) “Import price” means the price on which custom duty is to be payable by the
importer or by agent under the Custom Act, 1962(52 of 1962) and the Customs
Tariff Act, 1975 (51 of 1975) on clearance from the port.

[F. No. X.11014/20/2017-DRS]

(Sudhir Kumar)
Joint Secretary to the Government of India
Note.- The principal rules were published in the Gazette of India vide notification
No.F.28-10/45-H (1) dated 21stDecember, 1945 and last amended vide ---------.
 ANNEXURE- 4
Rule 150 E. Conditions of approval –An approval in Form 37 shall be subject to the following
general conditions: —

(f) The approved institution shall furnish reports of the results of test or analysis in Form 39 carried on
drugs / cosmetics on behalf of licensees for manufacturer of drugs/cosmetics. The approved
institution shall furnish reports of the results of test or analysis carried on drugs / cosmetics on behalf
of any other individuals or organizations other than licensees for manufacturer of drugs/cosmetics in
Form 39A.

FORM 39 A
[See rule 150E(f)]

Report of test or analysis by approved institution

(1) Name of inspector from whom received..............................................................
(2) Serial No. and date of Inspector’s memorandum.................................................
(3) Number of sample..............................................
(4) Date of receipt of the sample.................................................
(5) Name of drug / cosmetics / raw material purporting to be contained in the sample.
(5) Details of raw material/final product in bulk/final product (in finished pack)* as obtained from the
Inspector:
(a) Name of the Manufacturer and his Manufacturing Licence number under the act and rules
made thereof
(B) Original Manufacturer's name in the case of raw materials and drugs repacked.
(b) Batch number.
(d) Date of manufacture, if any.
(e) Date of expiry, if any.
(6) Results of test or analysis with protocols of test or analysis applied.
In the opinion of the undersigned, the sample referred to above is *of standard quality/is not of standard quality
as defined in the Act and the rules made thereunder for the reasons given below.
Date.................................. ......................................................
Signature of Person-in-charge of testing
Note:- Final product includes repacked material.
*Delete whichever is not applicable
 Annexure -5

RECOMMENDATIONS OF THE (REPRODUCTIVE AND UROLOGY) HELD ON

17.09.2013:-

The NDAC (R eproductive and Urology) deliberated the proposals on 17.09.2013 and
recommended the follow ing:-

Agenda
Drug Name Recom m endations
no.

Com m ittee opined that all Fixed Dose

Com bination injectable preparations containing
synthetic O estrogen and Progesterone were
prohibited in the country vide GSR No. 743(E)
dated 10.08.1989 m ost probably due to report
of misuse of such preparations for pregnancy
detection. In present scenario the chances of
such m isuse is not there as at present many
pregnancy detection kits which are very
sensitive and various m eans for satisfactory
contraception are available. ICMR has already
conducted the clinical trial with the cyclofem in
1275 subjects who were followed up for 10934
wom en- m onths of use. The clinical data has
been found satisfactory. Available data shows
that Fixed Dose Com bination injectable
preparations containing synthetic Oestrogen
and Progesterone (cyclofem ) are not
associated with change in Bone Mineral
Density. Therefore the committee
1 / Cyclofem recom m ended to consider de-notification of
banning of the Fixed Dose Combination
V .-''
injectable preparations containing synthetic
O estrogen and Progesterone by appropriate
authority. The com m ittee recom mended the
grant of perm ission of clinical trial of Cyclofem
and NET-EN subject to the following conditions:
1. The study should be titled as
extended phase III clinical trial.
2. The study should be conducted at
m ultispecialty hospitals having
em ergency facilities and
institutional ethics committee
registered with CDSCO.
3. Details of such sites along with
undertaking by the investigators
as per appendix VII of schedule Y
should be subm itted.
4. Informed consent docum ent as
per appendix V of schedule Y
should be subm itted.
5. U ndertaking as per Rule 122DAB
 for com pensation and providing
m edical m anagem ent as per the
Rule in case of injury/death in
clinical trial.
6. Denotification of the banning of
Cyclofem i.e. Fixed Dose
C om bination injectable
preparations containing synthetic
O estrogen and Progesterone
7. The recom m endation may be
placed before DTAB for further
consideration.
(Dr. Sunita Mittal and Dr. Lakbir
Dhaliwal did not take part in
decision making process due to
conflict of interest)
In protocol it is specifically m entioned that the
patients should be followed up to 7 days.
However, the firm failed to present the followed
up data for 7 days as per protocol. Further the
trial was conducted at single centre on 100
patients only.

The com m ittee opined that the clinical trial

2 Atosiben
report should include the followed data as per
the protocol. Trial should also be conducted in
at-least 500 patients at geographically
distributed m ultispecialty hospitals/m edical
college in which 50 % should be governm ent
hospital/m edical college clinical trial sites.
Accordingly protocol should be submitted to the
office of DCG (I) to review and approved.

The Firm presented G lobal clinical studies in

which India was also the part of global clinical
trial and 114 patients was included from India.
The com m ittee noted that drug has low side
effects as com pare to com parative drug used in
trail and it would increase the patient
com pliance. After deliberation the committee
recom m ended for the approval of drug for
3 im port and m arketing on the basis of presented
Mirabegron clinical study reports subject to the condition
tablets that firm should conduct Phase IV clinical trial
in at-least 500 patients at m ultispecialty
hospitals/m edical college having em ergency
facilities and registered institutional ethics
com mittee with CDSCO geographically
distributed in the country and 50 % of trial sites
should be governm ent hospital/m edical college.
A ccordingly protocol should be submitted to the
 com m ittee for review and approval.
(Dr. N. K. M ohanty did not take part in decision
making process due to conflict of interest)
The applicant subm itted reply in respect of
NDAC m eeting held on 16/3/2013 and
VSL#3 presented before the com mittee. The
com m ittee noted that earlier it was
recom m ended that “As far as project is
concerned rational of each constituents of the
form ulation to be used for the study should be
4 stated and accordingly the form ulation be
suggested. It is advised by the committee to
conduct proof of concept study initially through
vaginal route for UTI.” After deliberation the
com m ittee recom m ended for the conduct of
clinical trial by both routes vaginal and oral as
per subm itted Clinical Trial protocol.
The firm requested for the clinical trial wavier,
After deliberation the com m ittee recommended
the clinical trial waiver and for the approval of
drug for m anufacture and m arketing. FDC of
ethinylestradiol 20m cg+G estodene Tablets
75mcg is already approved.
The proposed FDC will have lesser adverse
Ethinylestradiol events due to reduction in amount of
5 +Gestodene Ethinylestradiol. However, firm should conduct
Tablets Phase IV clinical trial in at-least 500 subjects at
20m cg+75m cg m ultispecialty hospitals/m edical college having
em ergency facilities and registered institutional
ethics com m ittee with CDSCO geographically
distributed in the country and 50 % of trial sites
should be governm ent hospital/m edical college.
Accordingly protocol should be submitted to the
com m ittee for review and approval.

Dutasteride+Sil After detailed deliberation , com mittee opined

odosin Soft that com bi-kit of Dutasteride 0.5 m g+Silodosin
gelatine and is rational. However the firm is required to
6 hard gelatine conduct a 3 arm clinical trial with the proposed
capsule com bikit vis a vis individual drugs in a
0.5m g+4m g/8m significant num ber of subjects and accordingly
g proptcol etc. sholud be subm itted for review.

Although, Cyclofem product was earlier

approved in US and subsequently it was
7 discontinued from US m arket by Pfizer in 2004
due to com m ercial reasons following merger of
M/s Pharm ica and Upjohn with Pfizer as
informed by presenting firm ,the product is
 presently m arketed in countries like Latin
Estradiol Am erica, Hongkong & Indonesia etc. The drug
Cypionate + is also listed in W H O m odel list of essential
Medroxyproges medicines (18th list April 2013). ICMR has
terone Acetate already conducted the clinical trial with the
Injection cyclofem in 1275 subjects who were followed
0.5m g+4m g/8m up for 10934 w om en- m onths of use. The
g5m g/0.05m l+2 clinical data has been found satisfactory. The
5mg use of com bined progesterone and estrogen
(Cyclofem ) has not been found associated with
change in BMD. The com m ittee recom mended
that the product Estradiol Cypionate +
M edroxyprogesterone Acetate Injection
0.5m g+4m g/8m g5m g/0.05m l+25m g may be
approved for m arketing in the country subject
to de-notification of banning of drug. The
recom m endation may be placed before DTAB
for further consideration.
The product is already approved as
contraceptive pill and firm has proposed for
Desogestrel marketing the im ported product for additional
8 +Ethinylestradi indication- DUB. It was inform ed by the firm
ol tablet that the product is not approved in country of
0.15mg+0.03mg origin for the proposed additional indication.
Accordingly the com m ittee did not recommend
for the proposed additional indication.
The com m ittee recom m ended that a Phase III
9 Pergoveris trial shal be conducted and accordingly
protocol etc. shall be subm itted

Estradiol After deliberation, com m ittee recom mended for

10. Vaginal Tablets grant of perm ission for conduct of clinical trial
as per subm itted protocol.
 Experts Group meeting to review the status of monthly injectable
contraceptive ‘Cyclofem’ held on 25th October, 2017 in R. No. 309,
Committee Room, ICMR Hqrs

The following members participated in the meeting:

Expert Members

Dr. Soumya Swaminathan, Secretary DHR, MoHFW & DG, ICMR - Chairperson
Dr. S. K. Sikdar, Deputy Commissioner & OIC (FP), DHFW, MoHFW
Dr. A. K. Pradhan, Deputy Drugs Controller (India), FDA Bhavan, Delhi
Dr. Alka Kriplani, Prof and Head OBGyn, AIIMS, Delhi
Dr. Bikash Medhi, Professor Pharmacology, PGIMER, Chandigarh
Dr. Ankit Sharma, Asst Drugs Controller (India), FDA Bhavan, Delhi

ICMR
Dr. R. S. Sharma, Sci. ‘G’ & Head RBMCH
Dr. Shalini Singh, Sci. ‘F’, RBMCH
Dr. Malabika Roy, Consultant, RBMCH

Dr. Jagdish Prasad, DGHS and Dr Y. K. Gupta, Prof. and Head, Pharmacology,
AIIMS, Delhi, were unable to attend due to other commitments.

At the outset, Dr. Soumya Swaminathan, Secretary, DHR and DG, ICMR welcomed
the members and informed that this Expert group meeting was convened to review
the status of combined injectable contraceptive ’Cyclofem’ placed for approval to
DCGI In 2009 for a multisite Pre-programme Introductory study at 40 sites
throughout the country. One such combined injectable contraceptive Cyclofem has
been evaluated in a Phase-Ill trial and the report was submitted to DCGI in 2007.
Based on these results the Phase IV-Pre-Programme Introductory study was
proposed at the behest of the MoHFW in 2008. It was envisaged to evaluate the
logistics, training requirement, demand for the method and also validate the Phase
III study findings in the field situation and for Cyclofem’s probable inclusion in the
National Family Welfare Programme. She felt that since no decision has been taken
by the DCGI since 2013 on injectable contraception Cyclofem therefore there is an
urgent need to review the status of injectable contraceptive Cyclofem in presence of
representatives from DCGI, DGHS, Dept of HFW, MoHFW and subject Experts so
that a decision can be taken to take this product forward.

Page 1 of 4
Dr Sikdar appreciated that ICMR over the years has evaluated various newer
contraceptive methods including progesterone only and combined hormonal
methods for their safety, efficacy and acceptability in order to increase the
contraceptive choices available to women or couples in reproductive age desiring
family planning methods.

Dr. Y. K. Gupta conveyed through e-mail to DG, ICMR that it is unfortunate that such
huge effort has not been deliberated enough to arrive at a decision, He stated that
he was not aware of receiving any notification of the proposed committee by DTAB,
nor any meeting to discuss the issue and that he will be happy to contribute in any
possible manner to see that such a study does not go waste.

Dr. Roy presented the study findings of the Phase III study which was carried out in
controlled clinical trial'settings in 16 tertiary level multispecialty facilities regarding
efficacy, safety, acceptability and return of fertility in Cyclofem users. She infpjmed
that the report was evaluated by expert committees at ICMR and report submitted to
DCGI in 2007 with a suggestion for conducting pre-programme Introduction study.
She stated that the subsequent Phase IV Pre-programme Introductory study
proposal was approved by Research Advisory Council (RAC) of MOHFW in 2008
with financial support for being carried out at 31 Districts hospitals and 9 Mother
NGO (MNGO) clinics having written MOU with Tertiary level multispecialty hospitals
for back-up facilities. Following this ICMR obtained approval of ICMR Toxicology
Review Panel (TRP) and ICMR’s Ethics committee (IEC) in 2008 along with
Institutional Ethics committee approval from the participating sites. The proposal of
the Phase IV study along with TRP and IEC approvals was submitted to DCGI in
2009 for approval to conduct the study.

A comngunication received from the office of DCGI to ICMR on 17th December 2013,
informed'about the recommendations of NDAC held on 17th September 2013 and
the 65th meeting of DTAB held on 25th November 2013.

The NDAC recommended that a) the study be titled as an extended Phase III trial
and conducted through multi speciality hospitals having emergency facilities and
registered ethics committees, b) undertaking by Investigators and Informed consent
documents as per Appendix V of Schedule Y to be submitted, c) undertaking as per
Rule 122DAB for compensation^ and medical management as per rule in case of
injury /Death, d) denotification of Cyclofem ban i.e Fixed dose combination injectable
preparations of synthetic oestrogen and progesterone and that the recommendation
of NDAC be placed in the Drug Technical Advisory Board (DTAB) for further
consideration.

Page 2 of 4
The DTAB recommended the constitution of an Expert Committee with
Gynecologists, endocrinologists, pharmacologists under the Chairmanship of DGHS
to look into the essentiality of the Clinical Trial as well as the requirement if any, of
amendment of entry No 27 of the list of banned drugs in respect of fixed drug
combinations of Injectable preparations containing synthetic oestrogen and
progesterone in context of present day knowledge.

The Expert group deliberated on the study findings and historical scenario presented
during the meeting and the following observations were made:

Observations and comments of the Review Committee

- Cyclofem is available worldwide and is an approved product. Injectable
contraceptives are among the 4th most commonly used contraceptive in the
world.
- Members noted that Cyclofem has been added to the WHO Model List of
Essential Medicines in March 2007.
- Cyclofem has been approved by the US FDA in the year 2000 and was
marketed as Lunelle.
\ V
- Indian Medical eligibility criteria for Contraceptives (2015) include Cyclofem
as one of the products.
- Study data of Phase III study with Cyclofem carried out through 16 multi­
speciality hospitals indicates that Cyclofem is safe, efficacious (no
inadvertent pregnancy reported during the study period of one year), and
acceptable with continuation rate of 63.2 per 100 users at 12 months of use
Members noted that the return of fertility is 83% at the end of one year which
is comparable to fecundity in the normal population of 70-80% (Srinivasan K.
An application of a probability model to the study of inters live-birth intervals. Sankhya 1966,
Series 28: 175-82).

There were 2 (0.16%) stillbirths and one spontaneous abortion (0.0007%) in

women who became pregnant following discontinuation of Cyclofem use
during the follow up period of one year. However, in general population the
corresponding rates are much higher 10.0% (ACOG, 2015) for spontaneous
abortion and 2.2.1 pe.&1000 live births (WHO-PMNCH-2011) for still births in
India and, therefore these effects are unlikely to be related to product use.
Gynaecologists opined that the women in OPDs demand and prefer monthly
injectables for contraception, also the compliance with OCPs is reported to be
low, and therefore there is a great need for this product to be made available
in the country.

Page 3 of 4
 - NUVA ring which is also a combined hormonal contraceptive and is available
in the country (pharmacies) however, it is not affordable to most women in
India. Cyclofem is relatively inexpensive and will be affordable to the masses.
Besides, Cyclofem does not need self insertion unlike the ring, and may be
acceptable to some women.
- Combined oral and Injectable high dose preparations were banned in 1988
because of speculation of misuse and lack of diagnostic kits for pregnancy
detection at that time.
- The ban on fixed dose combined hormonal preparations in 1988 was due to
its misuse. Since then the scenario has changed and pregnancy detection kits
are freely available now, the members strongly recommended that
introduction of monthly injectable contraceptive is a national need and
therefore the process for denotification may be initiated at the earliest.
- The DCGI officials informed that a follow up meeting would be held,soon in
November, 2017.

Recommendations

• The Committee reviewed the entire sequence of application to the statutory

regulatory bodies inclbdinig the Phase-Ill study findings and noted that Injectable
contraceptive Cyclofem is safe, efficacious and acceptable to the women in India.

• The Committee was satisfied with the study study findings and hence unanimously
recommended that the DCGI should denotify the monthly combined injectable
contraceptive Cyclofem so that the product can be made available for the women in
the country.

The meeting ended with vote of thanks to the Chair.

Page 4 of 4
 Annexure -6

MINUTES OF THE 65™ MEETING OF DRUGS TECHNICAL ADVISORY BOARD

HELD ON 25™ NOVEMBER, 2013 IN THE CHAMBER OF DGHS, NIRMAN
BHAWAN, NEW DELHI - 110002

PRESENT
1. Dr. Jagdish Prasad, Chairman
Director General of Health Services,
Nirman Bhawan, New Delhi.

2. Shri C. Hariharan Member

Director in-charge,
Central Drugs Laboratory,
Kolkata-700016

3. Dr. J.A.S. Giri Member

815A, Road No. 41
Jublee Hills, Hyderabad-500033

4. Dr. C. Nath, Member

Central Drug Research Institute
Lucknow

5. Dr. Anshu Sethi Bajaj, Member

Medical Council of India,
New Delhi

6. Dr. B.P.S. Reddy, Member

CMD, Hetero Drugs Ltd.
Hyderabad

7. Dr. A. K. Tiwari Member

Indian Veterinary Research Institute
lzatnagar-243122 (U.P.)
value and having the end use for use in the human is considered as a drug. In view of
this the DTAB recommended that the class of drugs under item 1 of schedule D should
be amended to read as under:

“Substances not intended for medicinal use excluding those intended to be used
as drugs after further purification or rendering them sterile".

AGENDA NO. 13

CONSIDEARTION OF THE PROPOSAL TO GRANT PERMISSION FOR

CONDUCTING THE CLINICAL TRIAL OF AN INJECTABLE CONTRACEPTIVE
CYCLOFEM AND NET-EN BY ICMR

The Member Secretary, briefed the members that the office of DCG(I) had
received an application from Dr. Malabika Roy, Scientist-F, Division of RHN, ICMR,
New Delhi for conducting study entitled “Pre-programme introduction of Injectable
Contraceptive Cyclofem and NET-EN through district hospitals and NGO clinics- An
ICMR Task Force study."The NET-EN is Norethisterone Enanthate 200 mg as a two
monthly injectable hormonal contraceptive.

The “Fixed Dose Combination of Oestrogen and Progestin (other than oral
contraceptive) containing per tablet estrogen content of more than 50 meg (equivalent
to Norethisterone Acetate) and fixed dose combination injectable preparations
containing synthetic Oestrogen and Progesterone” was prohibited by the Ministry of the
Health and Family Welfare under section 26A of the Drugs and Cosmetics Rules, 1945
under entry number 27 of the list of banned drugs vide Gazette Notification G.S.R.
743(E) dated 10.08.1989.

Earlier a proposal of ICMR to conduct clinical trial in the country with the
injectable preparations containing Medroxyprogesterone acetate and estradiol
cypionate (Cyclofem) as monthly contraceptive was recommended by the DTAB in its
48th meeting held on 08th July, 1999 for the reason that the clinical trial could continue

23
without disturbing the present prohibitory status and the drugs would be imported for
limited purpose of clinical trial only.

The proposal was deliberated in 61st meeting of DTAB held on 24th July, 2012
also. The Board after deliberation recommended that an expert committee consisting of
Gynecologists, Pharmacologists may be constituted by the DCG(I) to examine the
safety and efficacy of Cyclofem especially in the light of the fact that such contraceptive
injections are prone to cause reduction in bone mineral density (BMD). The proposal of
was deliberated in New Drug Advisory Committee (NDAC) (Reproductive and Urology)
of the CDSCO on 17.09.2013. The Committee recommended for the grant of
permission of conducting clinical trial with Cyclofem and NET-EN subject to the
following condition:-

1. The study should be titled as extended phase III clinical trial.

2. The study should be conducted at multispecialty hospitals having
emergency facilities and Institutional Ethics Committee registered with
CDSCO.
3. Details of such sites along with Undertaking by Investigators as per
Appendix VII of Schedule Y should be submitted.
4. Informed Consent Documents as per appendix V of schedule Y should be
submitted.
5. Undertaking as per Rule 122DAB for compensation and providing medical
management as per the rule in case of injury/death in clinical trial.
6. Denotification of the banning of Cyclofem i.e. Fixed Dose Combination
Injectable preparations containing synthetic Oestrofen and Progesterone.
7. The recommendation may be placed before DTAB for further
consideration.
During deliberation the members were of the view that the proposal also
includes the requirement of the amendment of the entry number 27 of the list of
banned drugs also.
The DTAB recommended that an Expert Committee consisting of at least
three Gynecologists, three endocrinologists, Dr. Anoop Mishra and Dr. Y. K.
Gupta, HOD, Department of Pharmacology, AIIMS, New Delhi under the

24
Chairmanship of DGHS may be constituted to examine the essentiality of the
clinical trial as well as the requirement, if any, of the amendment of entry number
27 in respect of the FDC of injectable preprations containing synthetic oestrogen
and progesterone, in the context of present day knowledge.

Meeting ended with the vote of thanks to the Chair.

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