SCHEDULE Y : Latest Amendment

SCHEDULE Y
Drugs And CosmeticsAct 1940
and Rules 1945
Presented To:
Dr. (Prof.) S.K. Gupta
HOD Clinical Research
DIPSAR
Presented by:
Vishal kumar Biswkarma
M.Pharm
Clinical Research

OVERVIEW OF PRESENTATION
•The Drugs And Cosmetics Act, 1940 and Rule,1945
•The Drugs And Cosmetics Act, 1940(Amendments)
•ScheduleY –What it CoversAndAssociated Rules
•Responsibilities of Sponsor, Investigator And EthicsCommittee
•Application For Permission Under Form 44, Regulatory Authorities,Fees
•Clinical Trials
• Amendments in ScheduleY
•Appendices Of ScheduleY

THE DRUGS AND COSMETICS ACT,1940
•An Act to regulate import, manufacture, distribution and sale of drugs and
cosmetics.
•Passed by the Indian Parliament.
•It extends to the whole of India
•Both the Act and the Rules came into force from 10th April 1947
DRUGS & COSMETICS RULE 1945
•168 Rules has been divided in to Parts from I –XIX as per the different
subjects pertaining to
Schedule: An organized plan for matters to be attended to. (fromAtoY)
Act: A law or formal decision made by a parliament or other group of elected
law-makers.
Rule: An accepted principle or instruction that states the way things are or
should be done, and tells you what you are allowed or are not allowed todo

THE DRUGS AND COSMETICS
ACT, 1940 (AMMENDMENTS)
•The Drugs (Amendment) Act, 1955,
•Drugs and Cosmetics (Amendments) Act, 1964,
•The Drugs and Cosmetics (Amendments) Act, 1972,
•The Drugs and Cosmetics (Amendments) Act, 1995

DRUG REGULATORY LAWS
1940-Drugs and CosmeticAct
1985-Narcotic drugs and psychotropic substances act
research on human2000-Ethical guidelines for biomedical
subjects
2001-Indian GCP guidelines
2002 -Amendment to D & C act
2005-Revised scheduleY
Also:
vaccines,• Guidelines for pre-clinical data for r-DNA
diagnostics & biologicals.
• Draft guidelines for stem cell research/ regulation

SCHEDULE Y
• It states the requirements and guidelines
needed for getting permission to import or/and
manufacture new drug for sale or to undertake
clinical trials.
• It includes rules 122A, 122B, 122D, 122DA ,
122DAA and 122E

Schedule Y
SCOPE UTILITY
NEW DRUG DEVELOPMENT
PROCESS IN INDIA
RIGHTS/ SAFETYWELL
BEING OF HUMAN

DIFFERENT RULES
RULES PERMISSION/ SIGNIFICANCE
122A To import new drug
122B To manufacture new drug
122D To import or manufacture fixed dose
combinations
122DA To conduct clinical trials for a new
drug / investigational new drug
122DAA Definition of clinical trial
122E Definition of new drug

NEW DRUG (122 E)
A drug, as defined in the Act including bulk drugs substance which has not been
used in the country to any significant extent under the conditions prescribed,
recommended or suggested in the labelling thereof and has not been
recognised as effective and safe by the licensing authority mentioned under
rule 21 for the proposed claims.
INVESTIGATIONAL NEWDRUG
New chemical entity or a product having therapeutic indication but which has
never been earlier tested on human beings.
DEFINITION OF CLINICAL TRIAL(122-DAA)
“Clinical trial” means a systematic study of new drug(s) in human subject(s) to
generate data for discovering and/or verifying the clinical, pharmacological
(including pharmacodynamic and pharmacokinetic) and/or adverse effects
with the objective of determining safety and / or efficacy of the newdrug.”

APPLICATION FOR PERMISSION
• The application for import or manufacture of new drug for sale
or to undertake clinical trial is made in form no. 44
accompanied with the data
1. CHEMICAL AND PHARMACEUTICAL
INFORMATION
2. ANIMAL PHARMACOLOGYDATA
3. ANIMAL TOXICOLOGYDATA
4. HUMAN PHARMACOLOGICALDATA.
• If the study drug is intended to be imported for the purpose of
examination, test, or analysis, the application for import of
drug for such purpose should be made in form no. 12.

CHEMICAL ANDPHARMACEUTICAL
INFORMATION
1. INFORMATION ON ACTIVE
INGREDIENTS-
• Drugs information ( generic name ,
chemical name or INN)
2. PYSICOCHEMICAL DATA-
a) Chemical name & structure
(Empirical formula , molecular
weight)
b) Physical properties
(Description, solubility, rotation,
partition coefficient, dissociation
constant, m.p/b.p)
3. ANALYTICAL DATA-
a) Elemental analysis
b) Mass spectrum
c) IR spectrum
d) NMR spectrum
e) UV spectrum
f) Ploymorphic identification
4. COMPLETE MONOGRAPH
SPECIFICATIONS INCLUDING
-
a) Identification
b) Quantification of impurity
c) Enantiomeric purity
d) Assay

CHEMICAL AND
PHARMACEUTICAL INFORMATION
5. VALIDATION-
a) Assay method
b) Impurity estimation method
c) Other volatile impurities estimation
method
7. DATA ON FORMULATION-
Dosage form, composition, master
manufacturing formula, In process
quality control check, finished
product specifications, validation
of analytical method.
6. STABILITY STUDIES-
a) Final release specifications
b) Reference standard
specifications
c) Material safety data sheet

ANIMAL PHARMACOLOGY
1. SPECIFIC PHARMACOLOGICALACTIONS –
• These are those actions the demonstrate therapeutic potential for human.
• Studies conducted & their design made will be based on individual properties
& intended use of investigational drug.
2. GENENRAL PHARMACOLOGICALACTIONS–
a) Essential Safety Pharmacology:
 Are needed to be conducted to investigate potential undesirable
pharmacodynamic effects of a substance on physiological functions in relation
to exposure within therapeutic range and above.
 Its aim is to study effect of test drug on vital organ like –
 CVS : effect is studied on B.P, heart rate and electrocardiogram
 CNS : effect is studied on motor activity, behavioural changes , sensory &
motor reflexes & body temperature.
 RESPIRATORY SYSTEM : drug is tested for effect on respiratory rate ,
tidal volume & other important functions.

ANIMAL PHARMACOLOGY
ESSENTIAL SAFETY3. FOLLOW UP STUDIES FOR
PHARMACOLOGY-
 They provide accurate information like-
 For CVS : ventricular contractibility, effects of chemical mediators, and
their agonist & antagonist.
 For CNS : behavioural studies, learning, neurochemistryetc.
 For respiratory system : airway resistance, blood gases, bloodpH.
4. SUPPLEMENTAL SAFETY PHARMACOLOGY STUDIES-
 They are required to investigate the possible adverseeffects.
 For urinary system : volume, specific gravity, osmolarity, pH, creatinine
level.
 For ANS : to know about the binding to specific receptor of drug ,and effect
of direct stimulation of autonomic nerves and their effect on cardiovascular
response.

ANIMAL TOXICOLOGYSTUDIES
• Toxicology is concerned with the study of adverse effects of chemicals
(drugs) on living organism.
• OBJECTIVE :
I. Benefit- risk ratio can be calculated.
II. Prediction of therapeutic index.
 WHYANIMALSTUDYARE DONE ?
I. Pharmacological effects are same in man.
II. Toxic effects in species will predict adverse effect in man.
III. Giving high doses in animal improve predictability in man.
IV. Risk assessment can be made by comparison of test doses in test species
with predicted therapeutic doses in man.
THERAPEUTICINDEX= MAXIMUM TOLERATEDDOSE
MINIMUM CURATIVEDOSE

TYPES OF TOXICOLOGY
STUDIES
• Systemic toxicology studies.
1) Single dose studies
2) Repeated dose studies
• Reproductive toxicology studies.
1) Male fertility
2) Female reproduction & development studies
• Local toxicity studies
• Hyper sensitivity studies
• Carcinogenicity studies

SINGLE DOSE TOXICITY
STUDIES(ACUTE TOXICITY)
Lethal
PRELIMINARY
 Maximum Non
Dose(MNLD) determined.
 METHOD :
I. Tested on rodent species
II. 2 route of administration.
III. Oral dose of 2 g/kg or 10 times
of normal human dose.
IV. MNLD established.
V. Symptoms, signs reported.
VI. Microscopic & macroscopic
evaluation done
DEFINATIVE
 MTD , MLD & target organ of
toxicity determined.
 METHOD :
I. Group of 20 animals of either
sex dosed at MNLD.
II. 5 animals of each sex observed
for 48 hrs & then autopsy is
conducted.
III. Remaining 5 of each sex
observed for 14 days
 OBSERVATION is done on
body wt., pathological changes,
macroscopy & microscopy.

REPEATED DOSE STUDIES(SUB
ACUTE/ CHRONIC STUDIES)
• Two mammalian species are taken (one should be non-rodent).
• Long duration studies (30-180 days).
• Dose is dependent on dose-escalating studies.
• Drug administered by clinical route.
• Parameters that are monitored & recorded are-
1. Behavioral
2. Physiological
3. Biochemical
4. Microscopic observations

REPRODUCTIVE TOXICITY
STUDIES(MALE FERTILITY)
• METHOD INVOLVES THE STEPS –
one rodent species(rat) 3 dose group taken
(each with 6 adult male),
1 control groupdrug treatment by
clinical route (28-72) days
mated with females pregnant females examined
after 13 days of gestation
all male animals are sacrificedOBSERVATION :
of testis,
examined for
•Weight
epididymus
histology.
• Sperms examined for
motility & morphology.

FEMALE FERTILITY
• Drugs administered to both male (28 days) and female (14 days) before
mating.
SEGMENT I
Fertility and general reproductive performance study are
performed.
Teratogenicity
SEGMENT II
Implantation embryogenesis
SEGMENT III
PERI and POST- NATALstudies.
Fertility & early embryonic development (rat)
Embryo – foetal development (rat & rabbit)
PERI
NATAL
Post natal survival of offspring,
growth parameters, Vital senses,
Behavioural effects
POST
NATAL

LOCAL TOXICITYSTUDIES
• Required when the drug is administered by special route (other than oral)in
human.
• STUDY DESIGN :
1. Two species along with control used.
2. Dose dependent on dose escalating studies.
3. Three dose level used.

TYPES OF LOCAL TOXICITY STUDIES
DERMAL TOXICITYSTUDIES
Rats & Rabbits used.
Local signs (erythema , oedema),
histological examination are studied.
DERMAL PHOTO-TOXICITY
STUDIES
Guinea pigs are used.
Used in treatment of leucoderma.
Examination of erythema &
oedema formulation.
VAGINAL TOXICITYSTUDIES
rabbits / dogs used.
Any kind of swelling,
histopathological changes of vaginal
wall studied.
RECTAL TOLERANCE STUDIES
Rabbits / dogs used.
Signs of pain, blood ,mucosa,
histology examination of rectal
mucosa.

OCULAR TOXICITYSTUDIES
Albino rats used
Changes in cornea, iris, pupil,
aqueous humor studied.
PARENTERAL DRUGS
For i.v. / i.m. / s.c. / intra-dermal
injection.
site of injection examined grossly
& microscopically.
INHALATION TOXICITY
STUDIES
one rodent & non rodent species
taken.
acute, sub-acute, chronic studies
performed.
observation of respiration rate
done.
Histological examination of
respiratory passage , lung tissue.

ALLERGENICITY/ HYPERSENSITIVITY
• GUINEA PIG MAXIMIZATION TEST :
i. Determine maximum non irritant or minimum irritant dose.
ii. Evaluation of erythema and oedema.
 LOCAL LYMPH NODE ASSAY:
i. Mice of one sex (either male or female)
ii. Drug treatment given on ear skin.
iii. Auricular lymph node dissected after 5 days.
iv. Increase in H-thymidine used for evaluation.

CARCINOGENICITY
• These studies are performed on :
 drugs used for more than 6 months or frequent intermittent use for chronic
disease.
 Drug whose chemical structure indicates carcinogenicity.
 Therapeutic class of drug which produce positive carcinogeniceffect.
 CONDUCT OF STUDY:
 Group size of 50 animals of either sex at 3 dose level aretaken.
 Control group of double size are taken.
 Onset of tumor development is recorded.
 Usually such studies are carried out for 24 months in rats and 18 months in
mice (life span studies)

CARCINOGENICITY
• EVALUATION OF RESULT:
i. Incidences of cancer in control and test drug animals arestudied.
ii. Number of animal with single/ multiple tumors are recorded.
iii. Macroscopic changes observed
iv. Trends are recorded towards increasing incidences of cancer with
increasing doses of drug.

HUMAN CLINICAL PHARMACOLOGY
DATA
 For a new drug discovered in India, clinical trials are required to be carried
out from phase I.
• For new drug discovered in other countries, phase I data generated
outside India should be submitted to licensing authority, and then
permission may be granted to conduct phase III to market thedrug.
Application should accompany with it –
 Investigator’s brochure
 Proposed protocol
 Case record form
 Ethics committee clearance form
 Study subjects informed consent document
 Investigator undertaking
• Reports must be certified by principle investigator.
• Full prescribing information (package insert with information like generic
name, composition, dosage form, indications, contra-indications, use in
special population, warnings, precautions, overdose, shelf life, dose &
method of administration should be approved by licensing authority.

APPLICATION IN FORM 44
FORM 44
(See Rules 122A, 122B, 122D and 122DA)
Application for grant of permission to import or manufacture a New Drug or to
undertake clinical trial
I/We..……….. of ………..hereby apply for grant of permission for import and / or clinical
trial or for approval to manufacture of a new drug or fixed dose combination or
subsequent permission of already approved new drug. The necessary information / data
is given below :
A. Particulars of New Drug :
1.Name of the drug :
2.Dosage Form :
3.Composition of the formulation :
4.Test specifications :
Active ingredients :
Inactive ingredients :
5.Pharmacological classification of the drug :
6.Indications for which proposed to be used :
7.Manufacturer of the raw material :
8.Patent status :

B. Data submitted along with the application
a. Permission to market new drug
1. Chemical and Pharmaceutical information
2. Animal Pharmacology
3. Animal Toxicology
4. Human / Clinical Pharmacology
5. Exploratory ClinicalTrials
6. Confirmatory ClinicalTrials
7. Bioavailability / dissolution and stability data
8. Regulatory status in other countries
9. Marketing information : (a) Proposed product monograph(b) Drafts oflabels
and cartons
10. Application for test license :

b. Subsequent approval / permission for manufacture of alreadyapproved
new drug
1)Formulation :
i)Bioavailability / bioequivalence
ii)Name of the investigator / centre
iii)Source of raw materials and stability
2) Raw Material
•Manufacturing Method
•QC parameters, specifications, stability
•Animal toxicity
c. Approval / permission for FDC
1.Justification
2.P’cokinetic/ P’codynamicdata
3.Any other data

d. Subsequent approval or approval for new indication –new dosageform:
•Number and date of Approval alreadygranted
•Justification
•Data on safety, efficacy and quality
A total fee of Rs………………… has been credited to the Governmentunder
the Head of Account …… (receiptenclosed)
Date ……
Signature………
Designation…………..

FEES FOR APPLICATION
Import ff/ Mfg ff/ Import bulk+Mfg ffof
new drug
Rs50,000/-
Application by sameapplicant,
for modified dosageform or withnew
claim
Rs15,000/-
Secondaryapplicants after 1 yearof
approval
Rs15,000/-
Import / Mfg FDC Rs15,000/-
Conduct Clinical trial with ND/IND
–Phase I
–Phase II
–Phase III
Rs50,000/-
Rs25,000/-
Rs25,000/-

CLINICAL TRIALS
Definition (122 DAA)
 Clinical trials means a systematic study of new drug(s) in human
subjects to generate data for discovering and/ or verifying the clinical,
pharmacological and / or adverse effects with the objective of
determining safety and/ or efficacy of the newdrug.
The personnel involve in clinical trials-
 Regulatory authority
 Ethical committee
 Sponsor
 Investigator
 Subject
 Monitor

A HISTORIC TIMELINE OF
CLINICAL TRIALS
605-562 BC-Daniel and the three children were noticeably healthier and more
vivacious than those who were relegated to the wine and meatdiet.
1537-Ambroise Pare, He mixed egg yolk, turpentine and oil of rose and
noticed that the wounds heal fast.
1747-James Lind conducted the first controlled clinical trial on a group of
sailors suffering from scurvy. He found that lemon juice supplement
recovered from scurvy in just six days.
1863-Placebos are first used in clinical trials.
1923-Randomization is introduced to clinical trials.(Fisher and Macknzei)
1938- Sulphanilamide disaster (Elixer with diethyleneglycol as solvent
causes death 107 people including 100 children)
1944-Multicenter clinical trials are introduced.
1947-The Nuremberg Code is developed which outlines 10 basic statements
for the protection of human participants in clinicaltrials.
1962- Thalidomide disaster (international drug safetymonitoring)

1964-The Declaration of Helsinki is developed which outlines ethical codes
for physicians and protection of participants in clinical trials all over the
world.
1988-The U.S. FDA is provided more authority and accountability over the
approval of new drugs and treatments.
1990- ICH was assembled to help eliminate differences in drug development
requirements for three global pharmaceutical markets: The EU, Japan and
U.S.
2000-A Common Technical Document (CTD) is developed. The CTD acts asa
standard dossier used in Europe, Japan and the U.S. for proposing data
gathered in clinical trials to respective governingauthorities.

STAKEHOLDERS & THEIR
RELATIONSHIPS
SUBJECT
REGULATORY
AUTHORITY
SPONSOR
ETHICS
COMMITTEE
INVESTIGATOR

APPROVAL FOR CLINICAL
TRIALS :
 Trials must be initiated only after the protocol has
been approved by the ethics committee and then , the
permission has been granted by licensing authority
under rule 21(b).
 If any protocol amendments made before/during the
course of trial, should be notified in writing to
licensing authority along with approval from ethics
committee

RESPONSIBILITIES OF THE
SPONSOR
•Implementing and maintaining quality assurance systems -
Good Clinical Practice (GCP) Guidelines issued by CDSCO,
INDIA.
•Sponsors are required to submit a status report on the clinical
trial to the Licensing Authority at the prescribed periodicity
(annual).
•In case of studies prematurely discontinued for any reason
including lack of commercial interest in pursuing the new drug
application, a summary report should be submitted within 3
months.

RESPONSIBILITIES OF THE
SPONSOR
•The summary report should provide a brief description of the
study, the number of patients exposed to the drug, dose
and duration of exposure, details of adverse drug
reactions and the reason for discontinuation of the study or
non-pursuit of the new drug application.
•Any Unexpected Serious Adverse Event (SAE) occurring
during a clinical trial should be communicated promptly
(within 14 calendar days) by the Sponsor to the Licensing
Authority and to the other Investigator(s) participating in the
study.

RESPONSIBILITIES OF
INVESTIGATOR
•Responsible for the conduct of the trial according to
the protocol and the GCP Guidelines and also for
compliance.
•Standard operating procedures are required to be
documented by the investigators for the tasks performed
by them.
•Ensure that a equate medical care is provided to the
participant for any adverse events.
•Report all serious and unexpected adverse events to
the Sponsor within 24 hours and to the Ethics
Committee that accorded approval to the study protocol
within 7 working days of their occurrence.

RESPONSIBILITIES OF ETHICS
COMMITTEE
•Safeguard the rights, safety and well being of all trial
subjects.
•Particular care to protect the rights, safety and well being
of all exposed subjects.
•Obtain ‘Standard Operating Procedures’ and maintain
a record.
•Ongoing review based on periodic study progress reports.
•In case an ethics committee revoke sits approval it must
record the reasons for doing so and at once communicate
such a decision to the Investigator as well as to the
LicensingAuthority.

INFORMED CONSENT
The Investigator must provide information about the study
verbally as well as using a patient information sheet, in a
language that is non-technical and understandable by the
study subject.
The Subject's consent must be obtained in writing using an
'Informed Consent Form'. Both the patient information sheet as
well as the Informed Consent Form should have been
approved by the ethics committee and furnished to the
LicensingAuthority.

PHASES OF CLINICALTRIAL
0) Phase 0
Pharmacodynamic and pharmacokinetics in humans
1 ) Phase I
Human /Clinical Pharmacology
2)Phase II
Explanatory trials
3)Phase III
Confirmatory trials
4)Phase IV
Post marketing Surveillance

PHASE 0 TRIALS
These are the first-in-human trials.
Single sub-therapeutic doses of the study drug or treatment are given to a
small number of subjects to gather preliminary data on the agent's
pharmacodynamics (what the drug does to the body) and
pharmacokinetics (what the body does to the drugs).
A Phase 0 study gives no data on safety or efficacy, being by definition a dose
too low to cause any therapeutic effect. Drug development companies carry
out Phase 0 studies to rank drug candidates in order to decide which has the
best pharmacokinetic parameters in humans to take forward into further
development.

HUMAN/CLINICAL
PHARMACOLOGY (PHASE I)
• Perform initial human testing in 20-100 healthy volunteer (Male) for first
time to discover its safety
• Complete pharmacokinetics is studied along with pharmacodynamics,
side effects, and desired effects.
• The safe dose range is also determined.
• phase I of trials is to determine the maximum tolerated dose in humans.
Phase I trials are usually carried out by investigators trained in clinical
pharmacology and having the necessary facilities to closely observe and
monitor the subjects. These may be carried out at one or twocenters.

EXPLANATORY TRIALS (PHASE II)
• Drug’s effectiveness is tested in 100-500 patients with disease
condition .
• Trial is done to determine-
I. adverse effects & risks.
II. Analyze optimal dose strength.
III. If the drug working by expected mechanism as desired
In phase II trial a limited number of patients are studies carefully to
determine possible therapeutic use, effective dose range and
further evaluation of safety and pharmacokinetics.
Normally 10-12 patients should be studied at each dose level at 3-4
centers.

CONFIRMATORY TRIALS (PHASE III)
• Study the drug in larger number of patients (1,000-5,000) for marketing
approval.
• Study is done -
1. To completely confirm therapuetic benefits.
2. To Generate statistically significant data on safety, efficacy, overall
risk – benefit ratio.
3. Provide basic labelling instruction to ensure properuse.
The purpose of these trials is to obtain sufficient evidence about the efficacy
and safety of the drug in a larger number of patients, generally in
comparison with a standard drug and/or a placebo asappropriate.
If the drug is already approved/marketed in other countries, phase III data
should generally obtained on at least 100 patients distributed over 3-4
centers primarily to confirm the efficacy and safety of the drug, in Indian
patients when used as recommended in the product monograph for the
claims made.

STUDIES IN SPECIAL
POPULATIONGERIATRICS PAEDIATRICS PREGNANT AND
NURSING MOTHERS
They are included in
phase trails if-
disease intended to be
treated is a disease of
aging.
population to be treated
include geriatrics.
when new drug alter the
geriatric patient response
(with regard to their safety /
efficacy ).
such consents are
included in studies after
prior consideration of
medical product, disease
type, efficacy & safety.
If new drug can treat
serious / life threatening
diseases in both paediatrics
& geriatrics.
studies include – clinical
trials, relative
bioequivalence
comparison of
formulation with adult
one, ADME studies, dose
selection across all age
groups.
They should be included
in trials only when drug is
intended for use by
pregnant / nursing mother
or foetuses/ nursing infants.
Follow up data on
pregnancy, foetus & child
will be required pertaining
to the appropriate period of
that drug.
Excretion of drug & its
metabolites into human
milk should be examined
& infant should be
monitored.

POST-MARKETING
SURVEILLANCE (PHASE IV)
• After marketing, & prior usage of drug , companies monitor every data &
submit periodic report , including adverse events.
• These study evaluate long term safety of the newdrug.
On approval of a new drug, the importer or the manufacturer shall conduct
post-marketing surveillance study of that new drug after getting the
protocols and the names of the investigators approved by the Licensing
Authority as defined under clause (b) of Rule 21 during the initial period
of two years of marketing.
Objective behind conducting phase IV clinicaltrial-
1) To find out other drug adverse reaction after prolong use of drug
2) To asses drug- drug or drug-food interaction
3) To asses tolerability or development of resistance after prolong use of
drug
4) To estimate the possible ADR in a specific kind of group of population

POST MARKETING
SURVELLIANCE
• After the approval to market the product, new drug should be monitored for
clinical safety. For this applicant should furnish PERIODIC SAFETY
UPDATE REPORT (PSUR) in order to –
1) Report all relevant new information from appropriatesources.
2) Relate these data to patient exposure.
3) Summarize market authorization status in different countries & any
significant variation related to the safety.
4) Indicate if any change is needed in the product information to optimize the
use of product.
• All dosage form & formulation as well as indication for new drug must be
covered in one PSUR.
• PSUR shall be submitted every 6 months for first two years and
annually for another tow year after approval ofgrant.

PSUR-PERIODIC SAFETY UPDATE REPORT
A PSUR should be structured asfollows:
.(a) A PSUR include – title page, introduction, current world wide
authorization status, update of action for any safety reason, estimated
patient exposure, studies, other information, overall safety evauation,
concluion.
(b) Introduction,
(c) Current worldwide market authorization status,
(d) Update of actions taken for safety reasons,
(e) Changes to reference safety information,
(1) Estimated patient exposure,
(g) Presentation of individual case histories,
(h) Studies,
(I) Other information,
(j) Overall safety evaluation,
(k) Conclusion,
(I) Appendix providing material relating to indications, dosing, pharmacology
and other related information.

SCHEDULE Y 2005
Revised old
1. Application forpermission 1.1 Nature of Trials
2. Clinical trials 1. Clinical Trials
(1) Approval for clinicaltrial 1.2 Permission for Trials
(2) Responsibilities of sponsor 1.3 Responsibilities of sponsor/
investigator
(3) Responsibilities of investigator (s)
(4) Informed consent- New
(5) Responsibilities of ECs-New
(6) Phase I 5. Phase I
(7) Phase II 6. Phase II
(8) Phase III 7. Phase III
(9) Phase IV-New

3. Studies in special population 8. Special Studies
(1) Geriatric
(2) Pediatric
(3) Pregnant or nursing women
4. PostMarketing Surveillance 12. PostMarketing Surveillance
5. Specialstudies: BE/BA Studies-New
Data to besubmitted alongwiththe
applicationto conductclinical
trials/import/mfg of new drugsfor
marketingin the country
Data required to besubmitted with
applicationto for permissionto marketa
new drug
2.1 Information on activeingredient 2.3 Specifications of active andinactive
ingredients

2.2 Physiochemicaldata 2.1 Physiochemicalproportion
2.3 Analyticaldata-New
2.4 Monograph Specification 2.4 Testfor identification of active
ingredients and method of itsassay
2.5 Validation-New
2.7 Data on Formulation 2.2 and 2.4
3.4 Safety Pharmacology-New
4.3 Male Fertility Study-New
4.6 Allergenicity/Hypersensitivity-New
11. Sampleandtestingprotocol 10.3 Sampleandtestingprotocol

LatestAmendmentsIn 2013 ToThe
DrugsAndCosmeticsRule, 1945
Rule 122-DAB (appendix xii) Compensation for injury and death
during the clinical trial.
Rule 122 DAC Prerequisites required for a clinical trial to
be considered as adequate so as to grant
permission by the Licensing Authority to
be conducted on any human body.
Rule 122 DD Registration of the Ethics Committee as
specified in the Appendix VIII is
mandatory.

REPORT OF THE PROF. RANJIT
ROY CHAUDHURY EXPERT
COMMITTEEIn July 2013 by the Expert Committee constituted by the Ministry of Health and
Family Welfare, formulated policy and guidelines for approval of new drugs,
clinical trials and banning of drugs.
The actions taken by the Ministry based on the recommendations hereon
included:
 Clinical trials should be conducted in accredited sites by an accredited
Investigator with the oversight of accredited ECs.
 Registration of Ethics Committee is made mandatory (as per Rule 122 DD)
 Regarding the procedure for review and application of new drugs, New
Drug Advisory Committee.
 A computerized database of experts in each area will be generated which will
be updated every year based on specific selection criteria. These are renamed as
Subject Expert Committees.
 If India takes part in a global clinical trial for a new drug, approval should be
sought from the CDSCO before marketing the drug.

 The CDSCO will review applications for approval of clinical trials within
six months and ultimately bring down the timeline to one month.
 If at all, a placebo controlled trial needs to be done, it should be efficient;
ethical and appropriate.
 Audio-visual recording of the informed consent process will be
undertaken.
 An investigator cannot take part in over three trials at atime.
 Use of information technology shall be used at all points in the clinical
trial to ensure total transparency.
 If an investigator fails to report an SAE within 24 hours, he should give the
reason for delay to the satisfaction of the DCGI along with the SAE report.
 Amendments in Rules 122 DAB and Schedule XII are called upon
regarding compensation in injury or death discerned at a laterstage.
 Academic clinical trials may be approved by the Institutional Ethics
Committee.
 No restriction to the number of clinical trials carried out in the country and
no deletion of existing drugs needs to be done in case a new drug is
approved for a particular disease.
 Post marketing surveillance is to be conducted for 4 years as per
Schedule Y which needs to be extended for 6years.

In 2013, The Independent Expert Committee had already devised a formula for
compensation in case of clinical trial related death as:
Compensation= (B * F* R)/99.37
B= Base amount i.e. 8 lacs
F=Factor depending upon the age of the subject as per Annexure1
R= Risk factor depending upon the seriousness and severity of thedisease
0.5- terminally ill patient (expected survival not more than (NMT) 6months)
1.0 - Patient with high risk (expected survival between 6 to 24months)
2.0 Patient with moderate risk
3.0 Patient with mild risk
4.0 Healthy Volunteers or subject of norisk
In case of patients whose expected mortality is 90 % or more within 30 days,a
fixed amount of Rs. 2 lacs should be given.

APPENDIX UNDER SCHEDUE Y
APPENDIX I -Data submitted with application for permission to market a new
drug
APPENDIX IA-Data submitted grant of permission to import manufacture an
already approved new drug
APPENDIX II -Structure, Contents Format for Clinical Study Reports
APPENDIX III- Animal Toxicology (Non-clinical Toxicity Studies)
APPENDIX IV -Animal Pharmacology
APPENDIX V -Informed Consent
APPENDIX VI -Fixed Dose Combination (Fdcs)
APPENDIX VII -Undertaking by the Investigator
APPENDIX VIII -Ethics Committee (amended)
APPENDIX IX -Stability Testing of New Drugs

APPENDIX X -Contents of the Proposed Protocol for ConductingClinical
Trials
APPENDIX XI-Data Elements for reporting serious adverseevents
occuring in a clinical trial (New)
APPENDIX XII- Compensation in injury or death(New)

BIBLIOGRAPHY
• DRUGANDCOSMETICSACT1940 , RULES
1945 (ScheduleY)
• CDSCOGUIDELINES

SCHEDULE Y : Latest Amendment

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SCHEDULE Y : Latest Amendment