MINUTES OF 332ND MEETING OF REGISTRATION BOARD

HELD ON 05TH DECEMBER, 2023

Item Detail of Item Page No

No.

I. Confirmation of minutes of 331st meeting of Registration Board 2

II. Division of Pharmaceutical Evaluation & Registration 2-5
III. Division of Biological Evaluation & Research 5-37

Drug Regulatory Authority of Pakistan

T.F. Complex, Mauve Area, G-9/4
Islamabad.
------------

Minutes of 332nd meeting of Registration Board (05th December, 2023) |1

 332nd meeting of Registration Board was held on 05th December, 2023 in the Committee
Room, Drug Regulatory Authority of Pakistan, G-9/4, Islamabad.
The meeting was chaired by Dr. Muhammad Fakhruddin Aamir, Chairman,
Registration Board, DRAP. The meeting started with recitation of the Holy Verses.

Following members attended the meeting:

Lt. Gen.(R) Prof. Dr. Karamat A. Karmat, (HI-M, SI-M),

1. Former Surgeon General Pakistan, Rawalpindi (On line) Co-opted
Member
Mr. Muhammad Aslam, Additional Draftsman, M/o Law &
2. Justice, Islamabad. Member

Mr. Sartaj Khan, Drug Analyst. Rep of Director DTL, Govt.

3. of KP Member

4. Dr. Ali Jan, Director, DTL, Govt. of Baluchistan Quetta Member

5. Mr. Iftikhar A. Chaudhary, Hospital Pharmacist, Lahore Co-opted

(Online) Member
6. Syed Adnan Rizvi, Director DTL. Govt. of Sindh. Karachi Member
(online)
7. Mr. Ajmal Sohail Asif, Director, Director, QA&LT, DRAP, Member
Islamabad.
8. Mr. Abdul Ghaffar, Additional Director, Rep. of Director, Member
Division of BE&R
9. Ch. Zeeshan Nazir Bajar, Additional Director Secretary
Mr. Saadat Ali Khan, Deputy Director, Rep. of Director,
10. MD&MC Division Member

11. Dr. Qurban Ali, Ex-Director General, NVL, Veterinary Co-opted

Expert (Online) Member

Mr. Nadeem Alamgir (Pharma Bureau), Mr. Jalal-ud-Din Zafar (online), PPMA and Mr. Ziaulhaq
(PCDA) attended the meeting as observers.

Minutes of 332nd meeting of Registration Board (05th December, 2023) |2

Item No. I. Confirmation of Minutes of 331st meeting of Registration Board

331st meeting of Registration Board was held on 31st October, 2023 to 2nd November, 2023.
Accordingly, draft minutes of the meeting were prepared and circulated among the members through email
and Whatsapp group of Registration Board on 19th November, 2023 for their perusal / approval / comments
(if any) at the earliest except draft minutes of Biological Division. No comments received and fair minutes
were circulated on 20.11.2023. Hence minutes of 331st meeting of RB stand approved. Draft minutes of
Biological Division were circulated among the members through email and Whatsapp group of Registration
Board on 24th November, 2023 for their perusal / approval / comments (if any) at the earliest. No comments
received and fair minutes were circulated on 30.11.2023.

After approval of Chairman, Registration Board, approved minutes of 331st meeting of Registration
Board has been circulated among relevant Divisions / Sections for implementation / compliance of decisions.

Decision: Registration Board noted the information and unanimously confirmed the minutes of
331st meeting of Registration Board.

Item No. II Division of Pharmaceutical Evaluation & Registration

Case No.01 Suspension of Registration of Drugs in compliance with Directions of Drug Court
Rawalpindi.

Mr. Nadeem Babar Khan, Chairman /Judge Drug Court, Rawalpindi Division, Rawalpindi vide letter No. 194-
95/DC dated 07-08-2023 has referred the case No. 3995/Judl/DC/RWP/2019 with title “the state versus M/s.
Flow Pharmaceuticals(Pvt) Ltd., 17-Km, Sheikhupura Road, Lahore and others Case No.
3995/Judl/DC/RWP/2019” and states as under:

‘The above mentioned case has been filed against FLOW Pharmaceuticals (Pvt) Ltd, and others on
the charge of manufacturing and sale of substandard drug and for issuing false warranty. The accused
(C.E.O, Production Manager, QC Manager and Warrantor) being the alleged responsible officers of
the accused company at the relevant time are being summoned by this court but their service has not
yet been affected as they are intentionally hiding from the process of law. Since the firm is
manufacturer of drugs which require registration by DRAP. Therefore, you are directed to suspend
the registration of the all drugs being manufactured by the firm with immediate effect and restoration
of registration of drugs shall be subject to appearance of accused before the court and issuance formal
order of restoration by this court.’

The case was presented before the 331st meeting of Regsistration Board, wherein the Board decided as under:

Decision of 331st Meeting of the Board:-

"Registration Board referred the case to Licensing Division.”

Mr. Nadeem Babar Khan, Chairman Drug Court, Rawalpindi vide letter No. 276-77/DC, Rawalpindi
dated 07th November, 2023 has directed to Chairman, Registration Board to appear before the Court on 28th
November, 2023.

Minutes of 332nd meeting of Registration Board (05th December, 2023) |3

 In compliance Dr. Muhammad Fakhruddin Aamir, Chairman Registration Board appeared before the
Court on 28th November, 2023. The Chairman Drug Court, Rawalpindi has directed to comply direction of
court and submit compliance report on or before 11th November, 2023.

The case is presented before the Board in the light of directions of Mr. Nadeem Babar Khan,
Chairman Drug Court, Rawalpindi, please.

Decision: Registration Board deliberated on the matter in the presence of Mr. Muhammad Aslam,
Additional Draftsman, Ministry of Law & Justice, Islamabad in compliance with the directions of Drug
Court, Rawalpindi decided to suspend all the drug products registered in the name of M/s. Flow Pharma
(Pvt) Ltd. 17-Km Sheikhupura Road Lahore with immediate effect. The court further directed that the
registrations will remain suspend till appearance of accused persons before the Drug Court, Rawalpindi
and issuance of formal order for restoration of registrations of products by the Drug Court, Rawalpindi.
The Board further decided that in order to comply directions of Drug Court, Rawalpindi partial
minutes of the meeting of this case shall be issued today, positively.

Minutes of 332nd meeting of Registration Board (05th December, 2023) |4

Furthermore, letter of Drug Court, Rawalpindi regarding details of CNICs and whereabouts of the
technical staff of M/s. Eros Pharmaceuticals (Pvt) Ltd., Karachi has already been referred to Licensing
Division vide E-office Diary No. 898-Dir (PE&R) dated 22.11.2023.

Item No. II. Division of Biological Evaluation & Research

CASES OF DD-I (MR. MUHAMMAD KASHIF)

CHANGE IN MANUFACTURING SITE (Humulin R 100IU/mL vial).

M/s. Eli Lilly Pakistan (Pvt) Limited, Karachi has applied for the change in manufacturing site of their
already registered biological product as per following details:
Sr. Reg. No. Brand Name Existing Marketing Demanded New Manufacturing Site:
and date Authorization Holder
& Manufacturer
1. 008302 Humulin R, Manufacturer: Manufacturer & Product License
Dated 100IU/mL Vial M/s Eli Lilly and Holder (As per CoPP):
24-09-1985 Each vial Company Indianapolis, M/s. Gland Pharma Limited, Sy No.
contains: IN 46285, 143 to 148, 150 & 151, Near
Human insulin USA Gandimaisamma Cross Roads, D.P.
Regular Product License Holder: Pally, Dundigal Post, Dundigal -
(rDNA Origin) Not Mentioned Gandimaisamma Mandal, Medchal-
Malkajgiri District, Hyderabad - 500
043, Telangana, INDIA.
Product License Holder (As per
Agreement between M/s Eli Lilly &
M/s. Gland Pharma Limited & as per
Authorization letter and copy of New
submitted CoPP):
M/s Eli Lilly and Company
Indianapolis, IN 46285, USA.

The applications have been evaluated as per approved SOPs and tabulated below:
Documents required as per SOP Documents submitted by the firm
Application Submitted
Required fee. Fee of Rs. 150,000/-
Online Slip Number: 82260366338
Copy of registration letter and last renewal Submitted
status Copy of Registration letter to Ali Gohar and Company,
dated 24-09-1985.
Copy of transfer of Registration letter from Ali Gohar and
Company to M/s. Eli Lilly Pakistan (Pvt) Limited, dated
07-06-2000.
Copy of all renewals dated 04-05-2005, 26-04-2010, 05-
09-2014, 24-04-2015.
Copy of last renewal submission dated 11-05-2020 has
been submitted
Original and legalized Certificate of • Firm has submitted Original Legalized Indian CoPP for
Pharmaceutical Product as per WHO format Humulin R, 100IU/mL Vial – 10ml (Certificate#
for new manufacturer’s name OR Original 3920591/TS/2023) with issue date: 28.02.2023 valid until
and legalized GMP certificate of new 15.01.2026 issued by Drug Control Administration, India.
manufacturing site with free sale certificate • The CoPP specifies free sale status of applied product in
from regulatory body of country of origin. exporting country.
• The CoPP also confirms GMP compliant status of the
manufacturer.
Site Master file Submitted

Minutes of 332nd meeting of Registration Board (05th December, 2023) |5

 Revised Sole Agency Agreement and any Submitted
proof/evidence of the contract between
Product License Holder & manufacturer
(with changed/new name), where the
manufacturer and product license holder are
different entities
Comparative manufacturing process at two Submitted
sites
Manufacturing Process and Batch Analysis Submitted
Data of both Manufacturing Sites
Undertaking that provided information/ Submitted
documents are true & correct.
Copy of Approval is submitted by the firm that M/s. Gland Pharma Limited is approved by Korea Ministry of
Food and Drug Safety (MFDS) to Manufacture Humulin R and Korea is the member of PIC/S.
Copy of Contract is submitted between Eli Lilly and Company and M/s. Gland Pharma Limited to manufacture
Humulin R, 100IU/ml Vial.
In the submitted copy of contract, it is clarified that MAH Holder of the above stated product will be M/s Eli
Lilly.
Original Letter of Authorization submitted from Eli Lilly and Company USA for Eli Lilly Pakistan and
mentioning Gland Pharma their source of supply for Humulin 70/30 Vial.
The firm has submitted technology transfer report from M/s Eli Lilly to M/s. Gland Pharma Limited.
The pharmaceutical concerns has submitted copy of revised CoPP in which the Marketing Authorization
Holder is M/s Eli Lilly and Company Indianapolis, IN 46285, USA.

CHANGE IN MANUFACTURING SITE (Humulin N, 100IU/mL Vial)

M/s. Eli Lilly Pakistan (Pvt) Limited, Karachi has applied for the change in manufacturing site of their
already registered biological product as per following details:
2. Reg. No. Brand Name Existing Marketing Demanded New Manufacturing
and date Authorization Holder Site:
& Manufacturer
008300 Humulin N, Manufacturer: Manufacturer & Product License
Dated 100IU/mL Vial M/s Eli Lilly and Holder (As per CoPP):
24-09-1985 Each vial Company Indianapolis, M/s. Gland Pharma Limited, Sy No.
contains: IN 46285, 143 to 148, 150 & 151, Near
Human insulin USA Gandimaisamma Cross Roads, D.P.
NPH Isophane Product License Holder: Pally, Dundigal Post, Dundigal -
Suspension Not Mentioned Gandimaisamma Mandal, Medchal-
(rDNA Origin) Malkajgiri District, Hyderabad - 500
043, Telangana, INDIA.
Product License Holder (As per
Agreement between M/s Eli Lilly &
M/s. Gland Pharma Limited & as per
Authorization letter and copy of New
submitted CoPP):
M/s Eli Lilly and Company
Indianapolis, IN 46285, USA.

The applications have been evaluated as per approved SOPs and tabulated below:
Documents required as per SOP Documents submitted by the firm
Application Submitted
Required fee. Fee of Rs. 150,000/-
Online Slip Number: 971519155338
Copy of registration letter and last renewal status Submitted
Copy of Registration letter to Ali Gohar and
Company, dated 24-09-1985.
Copy of transfer of Registration letter from Ali
Gohar and Company to M/s. Eli Lilly Pakistan
(Pvt) Limited, dated 07-06-2000.

Minutes of 332nd meeting of Registration Board (05th December, 2023) |6

 Copy of all renewals dated 04-05-2005, 26-04-
2010, 24-04-2015.
Copy of last renewal submission dated 11-05-
2020 has been submitted

• Firm has submitted Original Legalized Indian

Original and legalized Certificate of Pharmaceutical
Product as per WHO format for new manufacturer’s CoPP for Humulin N, 100IU/mL Vial – 10ml
name OR Original and legalized GMP certificate of (Certificate# 3941082/TS/2023) with issue date:
new manufacturing site with free sale certificate 25.02.2023 valid until 15.01.2026 issued by Drug
from regulatory body of country of origin. Control Administration, India.
• The CoPP specifies free sale status of applied
product in exporting country.
• The CoPP also confirms GMP compliant status
of the manufacturer.
Site Master file Submitted
Revised Sole Agency Agreement and any Submitted
proof/evidence of the contract between Product
License Holder & manufacturer (with changed/new
name), where the manufacturer and product license
holder are different entities
Comparative manufacturing process at two sites Submitted
Manufacturing Process and Batch Analysis Data of Submitted
both Manufacturing Sites
Undertaking that provided information/ documents Submitted
are true & correct.

Copy of Approval is submitted by the firm that M/s. Gland Pharma Limited is approved by Korea Ministry of
Food and Drug Safety (MFDS) to Manufacture Humulin R and Korea is the member of PIC/S.
Copy of Contract is submitted between Eli Lilly and Company and M/s. Gland Pharma Limited to manufacture
Humulin N, 100IU/ml Vial.
In the submitted copy of contract, it is clarified that MAH Holder of the above stated product will be M/s Eli
Lilly.
Original Letter of Authorization submitted from Eli Lilly and Company USA for Eli Lilly Pakistan and
mentioning Gland Pharma their source of supply for Humulin 70/30 Vial.
The firm has submitted technology transfer report from M/s Eli Lilly to M/s. Gland Pharma Limited.

The pharmaceutical concerns have submitted copy of revised CoPP in which the the Marketing Authorization
Holder is M/s Eli Lilly and Company Indianapolis, IN 46285, USA.

Deferred cases in 331st Registration Board Meeting.

CHANGE IN MANUFACTURING SITE (Humulin 70/30, 100IU/mL Vial)

M/s. Eli Lilly Pakistan (Pvt) Limited, Karachi has applied for the change in manufacturing site of their
already registered biological product as per following details:
3. Reg. No. Brand Name Existing Marketing Demanded New Manufacturing Site and
and date Authorization Product License Holder:
Holder &
Manufacturer

Minutes of 332nd meeting of Registration Board (05th December, 2023) |7

 011149 Humulin 70/30, Manufacturer: Manufacturer & Product License Holder (As
Dated 100IU/mL Vial M/s Eli Lilly and per CoPP):
28-07- Company M/s. Gland Pharma Limited, Sy No. 143 to
1990 Each vial Indianapolis, IN 148, 150 & 151, Near Gandimaisamma Cross
contains: 46285, Roads, D.P. Pally, Dundigal Post, Dundigal -
70% human USA Gandimaisamma Mandal, Medchal-
insulin isophane Product License Malkajgiri District, Hyderabad - 500 043,
suspension, Holder: Telangana, INDIA.
30% human Not Mentioned Product License Holder (As per Agreement
insulin (rDNA between M/s Eli Lilly & M/s. Gland Pharma
Origin) Limited & as per Authorization letter):
M/s Eli Lilly and Company Indianapolis, IN
46285, USA.

The case has been evaluated as per approved Guidelines: Post Registration Variation Guidelines and tabulated
below:
Documents required as per Guidelines Documents submitted by the firm
Application Submitted
Required fee as per relevant SRO. Humulin 70/30, 100IU/mL Vial
Fee Challan of Rs. 150,000/-
Online Slip Number: 11740145 dated 09-05-2023 has
been submitted
Copy of registration letter and last renewal Submitted
status Copy of Registration letter to Ali Gohar and Company,
dated 28-07-1990.
Copy of transfer of Registration letter from Ali Gohar
and Company to M/s. Eli Lilly Pakistan (Pvt) Limited,
dated 07-06-2000.
Copy of all renewals dated 04-05-2005, 26-04-2010, 05-
09-2014, 24-04-2015.
Copy of last renewal submission dated 11-05-2020 has
been submitted
Original and legalized Certificate of • Firm has submitted Original Legalized Indian
Pharmaceutical Product as per WHO format for CoPP for Humulin 70/30, 100IU/mL Vial – 10ml
new manufacturer’s name OR Original and (Certificate# 4126448/TS/2023) with issue date:
legalized GMP certificate of new 06.04.2023 valid until 06.02.2026 issued by Drug
manufacturing site with free sale certificate Control Administration, India.
from regulatory body of country of origin. • The CoPP specifies free sale status of applied
product in exporting country.
• The CoPP also confirms GMP compliant status
of the manufacturer.
Site Master file Submitted
Revised Sole Agency Agreement and any Submitted
proof/evidence of the contract between Product
License Holder & manufacturer (with
changed/new name), where the manufacturer
and product license holder are different entities
Comparative manufacturing process at two Submitted
sites
Manufacturing Process and Batch Analysis Submitted
Data of both Manufacturing Sites
Undertaking that provided information/ Submitted
documents are true & correct.
Copy of Approval is submitted by the firm that M/s. Gland Pharma Limited is approved by Korea
Ministry of Food and Drug Safety (MFDS) to Manufacture Humulin 70/30 and Korea is the member of PIC/S.
Copy of Contract is submitted between Eli Lilly and Company and M/s. Gland Pharma Limited Limited to
manufacture Humulin 70/30, 100IU/ml Vial.
In the submitted copy of contract, it is clarified that MAH Holder of the above stated product will be M/s Eli
Lilly.
Minutes of 332nd meeting of Registration Board (05th December, 2023) |8
Original Letter of Authorization submitted from Eli Lilly and Company for Eli Lilly Pakistan and mentioning
Gland Pharma their source of supply for Humulin 70/30 Vial.
The firm has submitted technology transfer report from M/s Eli Lilly to M/s. Gland Pharma Limited.

Registration Board in its 307th meeting delegated its power/functions for Change of contract
manufacturer/ manufacturing site of already registered products to the Chairman Registration Board.

The case was placed in 331st Registration Board Meeting and the Registration Board decided as under.

Decision of 331st DRB: Registration Board deferred the case for following:

1) Submission of valid legalized CoPP indicating that M/s Eli Lilly USA is Market
Authorization Holder of Humulin 70/30, 100IU/mL Vial manufactured by M/s. Gland
Pharma Limited, Sy No. 143 to 148, 150 & 151, Near Gandimaisamma Cross Roads,
D.P. Pally, Dundigal Post, Dundigal - Gandimaisamma Mandal, Medchal-Malkajgiri
District, Hyderabad - 500 043, Telangana, INDIA.
2) Approval of product manufactured by M/s. Gland Pharma Limited, Sy No. 143 to 148,
150 & 151, Near Gandimaisamma Cross Roads, D.P. Pal)ly, Dundigal Post, Dundigal
-Gandimaisamma Mandal, Medchal-Malkajgiri District, Hyderabad - 500 043,
Telangana, INDIA in reference regulatory authorities.
3) Data as per DRAP notified post registration variation guideline for change of
manufacturing site.

The pharmaceutical concerns submitted Original and Legalized CoPP in which the Marketing Authorization
Holder is M/s Eli Lilly and Company Indianapolis, IN 46285, USA.

Decision: The Board was apprized that Special Investment and facilitation council, Prime Minister’s Office
vide letter No.F-5 (30) 09 / SIFC Islamabad dated 23rd November, 2023 has also forwarded
request of the company for support needed in the interest of diabetes patients.
Keeping in view data / documents / information alongwith original legalized CoPP clearly
indicating Marketing Authorization Holder as M/s Eli Lilly and Company Indianapolis, IN
46285, US, the Board acceded to request of the pharmaceutical concern for change of
manufacturing site from M/s Eli Lilly and Company Indianapolis, IN 46285, USA to M/s. Gland
Pharma Limited, Sy No. 143 to 148, 150 & 151, Near Gandimaisamma Cross Roads, D.P. Pally,
Dundigal Post, Dundigal - Gandimaisamma Mandal, Medchal-Malkajgiri District, Hyderabad -
500 043, Telangana, INDIA for already registered products namely; Humulin R 100IU/ml vial,
Humulin N 100IU/ml vial and Humulin 70/30 100IU/ml vial subject to submission of legalized
GMP certificate issued by Korea Ministry of Food & Drug Safety and compliance to current
import policy for finished drugs. Reference shall be sent to Cost & Pricing division for price
confirmation.

ADDITION OF MANUFACTURING SITE (Insulatard HM 100IU/mL, 10 mL Vial)

M/s Novo Nordisk Pharma (Pvt.) Limited, Karachi has applied for the addition of a manufacturing
site for their already registered biological products as per the following details:
4. Reg. No. Brand Name and Existing Registered Demanded Additional
and date Composition Manufacturing Site Manufacturing Site
010205 Insulatard HM M/s Novo Nordisk Eskayef Pharmaceuticals Limited,
Dated 100IU/ml, 10 ml Production SAS, 45 400 Squibb Road, Tongi Industrial
11-11- Vial. Avenue d’ Orleans, F- Area, Tongi, Ghazipur 1711,
2005 Suspension for 28000 Chartres, France. Bangladesh.
injection in 10ml
Vial.

The applications have been evaluated as per approved SOPs and tabulated below:
Documents required as per SOP Documents submitted by the firm
Application on Form-5F Submitted
Required fee as per relevant SRO. PKR 150,000/-: dated 03/02/2023
Deposit Slip No. 02835880

Minutes of 332nd meeting of Registration Board (05th December, 2023) |9

Copy of registration letter and last renewal status Registration letter: dated 11-11-2005
Renewal application 13-05-2010
Renewal application 16-04-2015
Site change 16-03-2017.
Copy of last renewal submission dated 04-05-2020
Original and legalized Certificate of Firm has submitted legalized copy of CoPP (No.
Pharmaceutical Product as per WHO format for DA/6-39/05/2408) dated 19-01-2023 issued by
new manufacturer’s name OR Original and Directorate General of Drug Administration. The
legalized GMP certificate of new manufacturing CoPP specifies free sale of the product in exporting
site with free sale certificate from regulatory country. The CoPP also confirms the GMP status of
body of country of origin. the firm
Site master file of new manufacturing site in case Submitted
of change of manufacturing site/ source
Revised Sole Agency Agreement when there is Submitted
change in MAH
Undertaking that provided information/ Submitted
documents are true & correct.

Form 5F Assessment report is as follows:

FORM 5-F ASSESSMENT REPORT

Insulatard® HM Vial 100IU/mL, 10 mL Vial.
Documents required as per SOP Documents submitted by the firm
Name, address of Applicant / Marketing M/s Novo Nordisk Pharma (Private) Limited,
Authorization Holder 113, Shahrah-e-Iran, Clifton, Karachi-75600., Pakistan
Details of Drug Sale License of importer Novo Nordisk Pharma (Pvt.) Limited
Address:
113, Shahrah-e-Iran, Clifton, Karachi, Pakistan.
Address of go-down:
208/1, Sector 23, KIA, Karachi
Validity: 09-04-2023
Status: License to sell drugs by way of Wholesale.
Name and address of marketing M/s Novo Nordisk A/S,
authorization holder/ Product License Novo Allé, DK-2880 Bagsværd, Denmark.
Holder (abroad)
Name, address of manufacturer(s) Eskayef Pharmaceuticals Limited
400 Squibb Road, Tongi Industrial Area,
Tongi, Gazipur 1711, Bangladesh
Name of exporting country Bangladesh
Detail of certificates attached (CoPP, CoPP:
Freesale certificate, GMP certificate) Firm has submitted legalized copy of CoPP (No. DA/6-
39/05/2408) dated 19-01-2023 issued by Directorate General
of Drug Administration Bangladesh.
The CoPP specifies free sale of the product in exporting
country.
The CoPP also confirms the GMP status of the firm.
Details of letter of authorization / sole Firm has submitted an attested and legalized letter of product-
agency agreement specific authorization from Senior Vice President
(Submissions and Life Cycle Management) of Novo Nordisk
A/S, Denmark. According to the letter, the firm Novo
Nordisk A/S, Denmark has a contract manufacturing site in
Bangladesh in name of Eskayef Pharmaceuticals. Further,
Novo Nordisk A/S has provided sole authorization to Novo
Nordisk Pharma (Private) Limited” to import, Distribute, and
sale the registered product Insulatard® HM Vial 100IU/ml 10
ml Vial. The letter was issued on 07-February-2023.

Minutes of 332nd meeting of Registration Board (05th December, 2023) | 10

Status of the applicant ☐ Manufacturer
☒ Importer
☐ Is involved in none of the above (contract giver)
Status of application ☒ New Drug Product (NDP)
☐ Generic Drug Product (GDP)
Intended use of pharmaceutical product ☒Domestic sale
☐ Export sale
☐Domestic and Export sales
For imported products, specify one the ☒ Finished Pharmaceutical product import
these ☐ Bulk import and local repackaging
☐ Bulk import and local repackaging for export purpose only
Dy. No. and date of submission Dy. No. 8142 dated 22-03-2023
Details of fee submitted PKR 150,000/-: dated 03/02/2023
Deposit Slip No. 02835880
The proposed proprietary name / brand
INSULATARD® HM 100 IU/ml, 10 ml Vial
name
Suspension for injection

Strength / concentration of drug of Active Active ingredient(s)

Pharmaceutical ingredient (API) per unit Insulin Human (rDNA) Ph.Eur. [Suspension of isophane
(NPH) insulin]

Quantity/100ml
383.142 mg (Eq. to 350.000 mg as 100% potency eq. to
10000 IU of Human insulin)

*Human insulin is produced in Saccharomyces cerevisiae by

recombinant DNA technology
Dosage form of applied drug Suspension for injection
Pharmacotherapeutic Group of (API) Drugs used in diabetes. Insulins and analogues for injection,
Intermediate-acting, insulin (human).
ATC code: A10AC01
Reference to Finished product
Ph. Eur Specs
specifications
Proposed Pack size Each Pack contains:
1 x 10ml Vial®
Proposed unit price MRP already available
Insulatard® HM Vial Reg.No.010205
Shelf Life 30 Months

Storage Conditions Store in refrigerator (2°C – 8°C).

The status in reference regulatory Novo Nordisk A/S holds registration in Reference
authorities Authorities. Eg: EMA & FDA
Novo Nordisk A/S, Denmark. According to the letter, the
firm Novo Nordisk A/S, Denmark has a contract
manufacturing site in Bangladesh in name of Eskayef
Pharmaceuticals. Further, Novo Nordisk A/S has provided
sole authorization to Novo Nordisk Pharma (Private)
Limited” to import, Distribute and sale the registered product
Insulatard®. The letter was issued on 07-February-2023
For generic drugs (me-too status) Not Applicable

Minutes of 332nd meeting of Registration Board (05th December, 2023) | 11

Module-II (Quality Overall Summary) Firm has submitted QOS as per ICH guidelines. Firm has
summarized information related to nomenclature, structure,
general properties, manufacturer, description of the
manufacturing process and process controls, control of
materials, control of critical steps and intermediates, process
validation and/or evaluation, manufacturing process
development, impurities, specifications, analytical
procedures and its validation, batch analysis and justification
of specification, reference standard or material, container
closure system and stability studies of drug substance and
drug product. The firm has also submitted non-clinical and
clinical overviews and summaries
Name, address of drug substance Address Activity
manufacturer
M/s Novo Nordisk A/S, Production of Master cell bank
Novo Allé, DK-2880 and working cell bank.
Bagsværd, Denmark. Storage of Master Cell Bank and
Working Cell Bank.

Novo Nordisk A/S Storage and stability testing of

Hallas Allé 4400 Master Cell Bank and Working
Kalundborg Cell Bank.
Denmark Recovery from fermentation
broth.
Purification of insulin human
Quality control of in-process
samples and drug substance.

Module-III Drug Substance: Firm has submitted detailed drug substance data related to
nomenclature, structure, general properties, solubilities,
physical state, manufacturers, description of manufacturing
process and controls, impurities, specifications, analytical
procedures and its validation, batch analysis and justification
of specification, reference standard or material, container
closure system and stability studies of drug substance.
Stability Studies of Drug Substance Firm has submitted stability study data of 3 batches of API at
(Conditions & duration of Stability long term and accelerated time conditions. The long-term
studies) stability data is conducted at -18°C±2°C for 60 months with
3 batches as per claim shelf life of 60 months. The accelerated
study conducted at +5 °C±3°C for 12 months.
Module-III (Drug Product): Firm has submitted data of drug product including its
description, composition, pharmaceutical development,
manufacture, manufacturing process and process control,
process validation protocols, control of excipients, control of
drug product, specifications, analytical procedures,
validation of analytical procedures, batch analysis,
justification of specifications, reference standard or
materials, container closure system and stability.
Analytical method validation/verification The firm has submitted analytical methods as per
of product specifications/Ph. Eur. The methods are validated as per
SOPs. The Analytical methods are listed below
Macroscopy (Ph. Eur.)
Microscopy (Ph. Eur.)
Identity of Human insulin (Ph. Eur.)
Assay of insulin (Ph. Eur.)
pH (Ph. Eur. / USP / JP)
Insulin in the supernatant (Ph. Eur.)
Minutes of 332nd meeting of Registration Board (05th December, 2023) | 12
 High molecular weight proteins (Ph. Eur. / USP)
A21 Desamido insulin (Ph. Eur.)
Other related impurities (Ph. Eur.)
Zinc total (Ph. Eur. / USP / JP)
Bacterial endotoxins (Ph. Eur. Method D)
Sterility (Ph. Eur. / USP / JP)
Total dissolved insulin (A2619a )
Isophane confirmation (A2361a)
Identity of preservatives (A2461a)
Phenol (A2461a)
Metacresol (A2461a)
Particulate matter (Ph. Eur. / USP / JP)
Container closure system of the drug The vial is made of colorless glass with a hydrolytic
product resistance as defined in Ph Eur and USP (type I glass). The
plunger is made of bromobutyl rubber.
Stability study data of drug product, shelf Firm has submitted comparability report for 3 PPQ batches
life and storage conditions of stability manufactured at site Chartres and at Contract
Manufacturing Site Eskayef stored for 30 months at long term
conditions at 5°C±3°C.
Module 4 & Module 5 No change Statement concerning to Module 4 and Module 5.
(Non-Clinical & Clinical Documentation)
1. The firm has not submitted any evidence that the applied product is registered in any reference
country.
2. The application has been sent to Legal Affairs Division, DRAP and their opinion regarding grant of
additional manufacturing site is still awaited.
Decision of 331st DRB: The Board noted that opinion of the legal division for grant of additional
manufacturing site is yet to come and therefore decided to defer the case and to place the matter before the
Board after seeking opinion from Legal Affairs Division of the DRAP.

The comments of Legal Affairs Division are as under:

“Reference para 289/N. The Registration Board, in its 330th meeting held on 24th to 26th July, 2023,
referred the matter of M/s Novo Nordisk Pharma (Pvt.) Limited, Karachi for the addition of a manufacturing
site for its already registered biological products. The existing manufacturing site is M/s Novo Nordisk
Production SAS, 45 Avenue d’ Orleans, F-28000 Chartres, France and the demanded additional
manufacturing site is M/s Eskayef Pharmaceuticals Limited, 400 Squibb Road, Tongi Industrial Area, Tongi,
Ghazipur 1711, Bangladesh.

The case has been examined and it is found that the law is silent on the issue of allowing an additional
manufacturing site for a registered product. Previously, during the pandemic of Covid-19, M/s Roche Pakistan
Limited, Karachi made a similar request which was considered in 295th meeting of the Registration Board
held on 8th to 11th June, 2020 and the Board approved the addition of M/s Genetech Inc., 4625 NE Brookwood
Parkway, Hillsboro, OR 97124, USA as manufacturing site for Actemra 400mg/20ml (Reg. No. 083136) as an
interim measure subject to certain conditions due to the fact that the firm’s global supply chain is unable to
fulfill the demand of many international markets from the existing manufacturing facility (M/s Utsunomiya
Plant of Chugai Pharma Manufacturing Co., Limited, 16-3, Kiyohara Kogyodanchi, Utsunomiya-city,
Tochigi, Japan).

The instant case may be considered in light of the aforesaid decision of the Registration Board as
insulins are included in the Model List of Essential Medicines – 23rd List (2023) published by the World Health
Organization (WHO) and notified by the Ministry of National Health Services, Regulations and Coordination
vide Notification No. F.8-43/2021-DD(PS) dated 2nd October, 2023 under paragraph 2(1)(xi) of the Drug
Pricing Policy, 2018.

The Registration Board may develop guidelines for allowing additional manufacturing sites keeping
in view the safety, efficacy and quality parameters of a product.”

Minutes of 332nd meeting of Registration Board (05th December, 2023) | 13

ADDITION OF MANUFACTURING SITE (Actrapid HM 100 IU/mL, 10 mL Vial)
Case: M/s Novo Nordisk Pharma (Pvt.) Limited, Karachi has applied for the addition of a manufacturing
site for their already registered biological products as per the following details:
5. Reg. No. Brand Name and Existing Registered Demanded Additional
and date Composition Manufacturing Site Manufacturing Site
010204 Actrapid HM 100 M/s Novo Nordisk M/s Eskayef Pharmaceuticals
Dated IU/mL, 10 mL Vial Production SAS, 45 Limited,
11-11-2005 Suspension for Avenue d’ Orleans, F- 400 Squibb Road, Tongi Industrial
injection in 10mL 28000 Chartres, France. Area, Tongi, Ghazipur 1711,
Vial. Bangladesh.
The application has been evaluated as per approved SOPs and tabulated below:
Documents required as per SOP Documents submitted by the firm
Application on Form-5F Submitted
Required fee as per relevant SRO. PKR 150,000/-: dated 03/02/2023
Deposit Slip No. 25106201728
Copy of registration letter and last renewal Registration letter: dated 11-11-2005
status Renewal application 13-05-2010
Renewal application 16-04-2015
Site change letter dated 06-03-2017
Copy of last renewal submission dated 04-05-2020
Original and legalized Certificate of The firm has submitted legalized of CoPP (No. DA/6-
Pharmaceutical Product as per WHO format 39/05/2410) dated 19-01-2023 issued by the Directorate
for new manufacturer’s name OR Original and General of Drug Administration Mohakhali, Dhaka-
legalized GMP certificate of new 1212. The CoPP specifies free sale status of the product
manufacturing site with free sale certificate in the exporting country. The CoPP also confirms the
from regulatory body of country of origin. GMP status of the firm.
Site master file of new manufacturing site in Submitted
case of change of manufacturing site/ source
Revised Sole Agency Agreement when there Submitted
is change in MAH
Undertaking that provided information/ Submitted
documents are true & correct.

FORM 5-F ASSESSMENT REPORT

Actrapid® HM 100 IU/mL, 10 mL Vial
Documents required as per SOP Documents submitted by the firm
Name, address of Applicant / Marketing M/s Novo Nordisk Pharma (Private) Limited,
Authorization Holder 113, Shahrah-e-Iran, Clifton, Karachi-75600
Pakistan
Details of Drug Sale License of Importer Novo Nordisk Pharma (Pvt.) Limited
Address:
113, Shahrah-e-Iran, Clifton, Karachi, Pakistan.
Address of go-down:
208/1, Sector 23, KIA, Karachi
Validity: 09-04-2023
Status: License to sell drugs by way of Wholesale.
Name and address of marketing authorization M/s Novo Nordisk A/S,
holder/ Product License Holder (abroad) Novo Allé, DK-2880 Bagsværd, Denmark.
Name, address of manufacturer(s) Eskayef Pharmaceuticals Limited
400 Squibb Road, Tongi Industrial Area,
Tongi, Gazipur 1711, Bangladesh
Name of exporting country Bangladesh
Detail of certificates attached (CoPP, CoPP:
Freesale certificate, GMP certificate) Firm has submitted legalized copy of CoPP (No. DA/6-
39/05/2410) dated 19-01-2023 issued by Directorate General
of Drug Administration Mohakhali, Dhaka-1212. The CoPP

Minutes of 332nd meeting of Registration Board (05th December, 2023) | 14

 specifies free sale status of the product in the exporting
country. The CoPP also confirms the GMP status of the firm.
Details of letter of authorization / sole agency Firm has submitted attested and legalized letter of product
agreement specific authorization from Senior Vice President
(Submissions and Life Cycle Management) of Novo Nordisk
A/S, Denmark. According to the letter, the firm Novo
Nordisk A/S, Denmark has a contract manufacturing site in
Bangladesh in name of Eskayef Pharmaceuticals. Further,
Novo Nordisk A/S has provided sole authorization to Novo
Nordisk Pharma (Private) Limited” to import, Distribute and
sale the registered product Actrapid® HM Vial 100IU/ml 10
ml Vial. The letter was issued on 07-February-2023.
Status of the applicant ☐ Manufacturer
☒ Importer
☐ Is involved in none of the above (contract giver)
Status of application ☒ New Drug Product (NDP)
☐ Generic Drug Product (GDP)
Intended use of pharmaceutical product ☒Domestic sale
☐ Export sale
☐Domestic and Export sales
For imported products, specify one the these ☒ Finished Pharmaceutical product import
☐ Bulk import and local repackaging
☐ Bulk import and local repackaging for export purpose only
Dy. No. and date of submission Dy. No. 8141 dated 24-03-2023
Details of fee submitted PKR 150,000/-: dated 03/02/2023
Deposit Slip No. 25106201728
The proposed proprietary name / brand name ACTRAPID® HM 100 IU/mL, 10 mL Vial
Solution for injection
Strength/concentration of drug of Active Active ingredient(s)
Pharmaceutical ingredient (API) per unit Insulin Human (rDNA) Ph.Eur.

Quantity /100Ml
383.142 mg (Eq. to 350.000 mg as 100 % potency eq. to
10000 IU of Human insulin)

*Human insulin is produced in Saccharomyces cerevisiae by

recombinant DNA technology
Dosage form of applied drug Solution for injection
Pharmacotherapeutic Group of (API) Drugs used in diabetes. Insulins and analogues for injection,
fast-acting, insulin (human).
ATC code: A10AB01.
Reference to Finished product specifications Ph. Eur Specs
Proposed Pack size Each Pack contains:
1 x 10mL Vial®
Proposed unit price MRP already available
Actrapid® HM Vial Reg.No.010204
Shelf Life 30 Months
Storage Conditions Store in refrigerator (2°C – 8°C).

The status in reference regulatory authorities Novo Nordisk A/S holds registration in Reference
Regulatory Authorities. Eg: EMA & FDA

Minutes of 332nd meeting of Registration Board (05th December, 2023) | 15

 Novo Nordisk A/S, Denmark. According to the letter, the
firm Novo Nordisk A/S, Denmark has a contract
manufacturing site in Bangladesh in name of Eskayef
Pharmaceuticals. Further, Novo Nordisk A/S has provided
sole authorization to Novo Nordisk Pharma (Private)
Limited” to import, Distribute and sale the registered product
Insulatard®. The letter was issued on 07-February-2023
For generic drugs (me-too status) Not Applicable

Module-II (Quality Overall Summary) Firm has submitted QOS as per ICH guidelines. Firm has
summarized information related to nomenclature, structure,
general properties, manufacturer, description of
manufacturing process and process controls, control of
materials, control of critical steps and intermediates, process
validation and/or evaluation, manufacturing process
development, impurities, specifications, analytical
procedures and its validation, batch analysis and justification
of specification, reference standard or material ,container
closure system and stability studies of drug substance and
drug product. The firm has also submitted the non-clinical
and clinical overviews and summaries
Name, address of drug substance Address Activity
manufacturer
M/s Novo Nordisk A/S, Production of Master cell bank
Novo Allé, DK-2880 and working cell bank.
Bagsværd, Denmark Storage of Master Cell Bank
and Working Cell Bank.
M/s Novo Nordisk A/S, Storage and stability testing of
Novo Allé, 4400 Master Cell Bank and Working
Kalundborg, Denmark. Cell Bank.
Recovery from fermentation
broth.
Purification of insulin human
Quality control of in-process
samples and drug substance.
Module-III Drug Substance: Firm has submitted detailed drug substance data related to
nomenclature, structure, general properties, solubilities,
physical state, manufacturers, description of manufacturing
process and controls, impurities, specifications, analytical
procedures and its validation, batch analysis and justification
of specification, reference standard or material, container
closure system and stability studies of drug substance.
Stability Studies of Drug Substance Firm has submitted stability study data of 3 batches of API at
(Conditions & duration of Stability studies) long term and accelerated time conditions. The long term
stability data is conducted at -18°C±2°C for 60 months with
3 batches as per claim shelf life of 60 months. The accelerated
study conducted at +5 °C±3°C for 12 months.
Module-III (Drug Product): Firm has submitted data of drug product including its
description, composition, pharmaceutical development,
manufacture, manufacturing process and process control,
process validation protocols, control of excipients, control of
drug product, no change statement concerning to Actrapid®
100IU/ml,10 ml, specifications, analytical procedures,
validation of analytical procedures, batch analysis,
justification of specifications, reference standard or
materials, container closure system and stability.

Minutes of 332nd meeting of Registration Board (05th December, 2023) | 16

Analytical method validation/verification of The firm has submitted analytical methods as per
product specifications/Ph. Eur. The methods are validated as per
SOPs. The Analytical methods are listed below
Macroscopy (Ph. Eur.)
Microscopy (Ph. Eur.)
Identity of Human insulin (Ph. Eur.)
Assay of insulin (Ph. Eur.)
pH (Ph. Eur. / USP / JP)
Insulin in the supernatant (Ph. Eur.)
High molecular weight proteins (Ph. Eur. / USP)
A21 Desamido insulin (Ph. Eur.)
Other related impurities (Ph. Eur.)
Zinc total (Ph. Eur. / USP / JP)
Bacterial endotoxins (Ph. Eur. Method D)
Sterility (Ph. Eur. / USP / JP)
Total dissolved insulin (A2619a )
Isophane confirmation (A2361a)
Identity of preservatives (A2461a)
Phenol (A2461a)
Metacresol (A2461a)
Particulate matter (Ph. Eur. / USP / JP)
Container closure system of the drug product The vial is made of colorless glass with a hydrolytic
resistance as defined in Ph Eur and USP (type I glass). The
plunger is made of bromobutyl rubber.
Stability study data of drug product, shelf life Firm has submitted comparability report for 3 PPQ batches
and storage conditions of stability manufactured at site Chartres and at Contract
Manufacturing Site Eskayef stored for 30 months at long
term conditions at 5°C±3°C.
Module 4 & Module 5 No change Statement concerning to Module 4 and Module 5.
(Non-Clinical & Clinical Documentation)
1. The firm has not submitted any evidence that the applied product is registered in any reference
country.
2. The application has been sent to Legal Affairs Division, DRAP and their opinion regarding grant of
additional manufacturing site is still awaited.

Decision of 331st DRB: The Board noted that opinion of the legal division for grant of additional
manufacturing site is yet to come and therefore decided to defer the case and to place the matter before the
Board after seeking opinion from LegalAffairs Division of the DRAP.

The comments of Legal Affairs Division are as under:

Reference para 289/N. The Registration Board, in its 330th meeting held on 24th to 26th July, 2023,
referred the matter of M/s Novo Nordisk Pharma (Pvt.) Limited, Karachi for the addition of a manufacturing
site for its already registered biological products. The existing manufacturing site is M/s Novo Nordisk
Production SAS, 45 Avenue d’ Orleans, F-28000 Chartres, France and the demanded additional
manufacturing site is M/s Eskayef Pharmaceuticals Limited, 400 Squibb Road, Tongi Industrial Area, Tongi,
Ghazipur 1711, Bangladesh.

The case has been examined and it is found that the law is silent on the issue of allowing an additional
manufacturing site for a registered product. Previously, during the pandemic of Covid-19, M/s Roche Pakistan
Limited, Karachi made a similar request which was considered in 295th meeting of the Registration Board
held on 8th to 11th June, 2020 and the Board approved the addition of M/s Genetech Inc., 4625 NE Brookwood
Parkway, Hillsboro, OR 97124, USA as manufacturing site for Actemra 400mg/20ml (Reg. No. 083136) as an
interim measure subject to certain conditions due to the fact that the firm’s global supply chain is unable to
fulfill the demand of many international markets from the existing manufacturing facility (M/s Utsunomiya
Plant of Chugai Pharma Manufacturing Co., Limited, 16-3, Kiyohara Kogyodanchi, Utsunomiya-city,
Tochigi, Japan).

Minutes of 332nd meeting of Registration Board (05th December, 2023) | 17

 The instant case may be considered in light of the aforesaid decision of the Registration Board as
insulins are included in the Model List of Essential Medicines – 23rd List (2023) published by the World Health
Organization (WHO) and notified by the Ministry of National Health Services, Regulations and Coordination
vide Notification No. F.8-43/2021-DD(PS) dated 2nd October, 2023 under paragraph 2(1)(xi) of the Drug
Pricing Policy, 2018.

The Registration Board may develop guidelines for allowing additional manufacturing sites keeping
in view the safety, efficacy and quality parameters of a product.

Decision: Registration Board deliberated the matter in detail. Representative from M/o Law and
Justice, Islamabad opined that there is no provision under law to grant additional
manufacturing site. Accordingly keeping in view legalized CoPP, availability of product in
country of origin i.e. Bangladesh & MA Holder on CoPP i.e M/s Novo Nordisk, Denmark and
release of batch from manufacturer, after approval from MA Holder i.e M/s Novo Nordisk,
Denmark, Registration Board, decided to approve new manufacturing site i.e., M/s Eskayef
Pharmaceuticals Limited, 400 Squibb Road, Tongi Industrial Area, Tongi, Ghazipur 1711,
Bangladesh for Insulatard HM 100IU/mL, 10 mL Vial and Actrapid HM 100 IU/mL, 10 mL
Vial, subject to compliance of current import policy for finished drugs. Moreover, reference
shall be sent to cost & pricing division for confirmation of price. The Board further decided
to call the management for personal hearing to initiate the process of cancellation of said
products from existing site i.e. M/s Novo Nordisk, France.

Priority / Out of Queue consideration of Heparin & Enoxaparin Injections

DRAP Authority in its 144th meeting held on 26-08-2022 while considering the shortage of Heparin
& Enoxaparin injections decided as follows:
“The Authority, as a one-time exercise, approved out of queue consideration of submitted
registration applications of following drugs in order to ensure their smooth and continuous supply in the
market:
Paracetamol (Tablets, lnfusion and Syrup / Suspension)
Albumin bound Paclitaxel lnjection
Heparin and Enoxaprin lnjection
PE&R and BE&R Divisions are advised to process the cases of abovementioned drugs without
waiting for formal approval of minutes.”

Imported Heparin Injection from non-Reference countries:

Name, address of Applicant / M/s Hakimsons (Impex) (Pvt.) Ltd.,
6. Marketing Authorization Holder Address: Hakimsons Building, 19 T-30 West Wharf Road
Karachi 74000 Pakistan
Product license holder LABORATORIOS FARMACEUTICOS ROVI, S.A.
Julián Camarillo, 35
28037 Madrid – Spain
Name, address of Manufacturing site. Manufacturing and primary and secondary
packaging site of the finished product;

ROVI PHARMA INDUSTRIAL SERVICES, S.A.

Paseo de Europa, 50, San Sebastian de los Reyes
28703 Madrid-Spain

Batch control and batch Release site;

ROVI PHARMA INDUSTRIAL SERVICES,
S.A./ Julián Camarillo, 35
28037 Madrid – Spain

Marketed by;
Merilios Global Private Ltd.
16th Floor, Hoechst House, Nariman Point,
Mumbai- 400-021, Maharashtra, India.
Minutes of 332nd meeting of Registration Board (05th December, 2023) | 18
 Name of exporting country Spain
Status of the applicant ☒ Importer
☐ Manufacturer
☐ Is involved in none of the above (contract)
Status of application ☐ New Drug Product (NDP)
☒ Generic Drug Product (GDP)
Intended use of pharmaceutical ☒ Domestic sale
product ☐ Export sale
☐ Domestic and Export sales
Dy. No. and date of submission Diary No. 982 dated 18th October 2023.
Details of fee submitted PKR 150000.0/- Dated 27/09/2023
The proposed proprietary name / brand
Heparin Rovi 1000 IU/ml
name
Strength / concentration of drug of Each 5ml vial contains:
Active Pharmaceutical ingredient Heparin Sodium………….5000 IU
(API) per unit
Pharmaceutical form of applied drug Solution for injection
Pharmacotherapeutic Group of (API) Injectable anticoagulants drugs (B01A2),
ATC Code: B01AB, antithrombotic
Reference to Finished product
Ph.Eur Specifications
specifications
Proposed Pack size Box of 100 Vial of 5ml
Proposed unit price 4.20 € /vial
The status in reference regulatory Heparin Sodium Solution for injection 1000IU/ml is
authorities Registered in the country of the origin Spain.
Drug Name: HEPARIN SODIUM, API: HEPARIN
SODIUM, Strength: 10,000 IU/ml. Dosage Form:
INJECTABLE;INJECTION, Company Name: FRESENIUS
KABI USA
For generic drugs (me-too status) Gratin Inj, 1000IU/ml, Reg. No. 085774
GMP status of the Finished product Firm has submitted Legalized GMP certificate
manufacturer (ES//110HVI/2Ib) valid till dated 03-06-2024
Name and address of API Yantai Dongcheng Biochemical Co., Ltd.
manufacturer. No.07, Changbaishan Road, Yantai Development Zone,
Shandong Province, P.R. China.
Module-II (Quality Overall Summary) Firm has submitted QOS as per WHO QOS-PD template.
Firm has summarized information related to nomenclature,
structure, general properties, solubilities, physical form,
manufacturers, description of manufacturing process and
controls, specifications, analytical procedures and its
validation, batch analysis and justification of specification,
reference standard, container closure system and stability
studies of drug substance and drug product.
Module III (Drug Substance) Firm has submitted detailed drug substance data related to
nomenclature, structure, general properties, solubilities,
physical form, manufacturers, description of manufacturing
process and controls, specifications, analytical procedures and
its validation, batch analysis and justification of specification,
reference standard, container closure system and stability
studies of drug substance.
Stability studies Stability study conditions:

Minutes of 332nd meeting of Registration Board (05th December, 2023) | 19

 Real time: 25°C ± 2°C / 60 ± 5%RH
Accelerated: 40°C ± 2°C / 75 ± 5%RH
Batches: (Real time: 25 ± 2 °C / 60 ± 5%RH
Accelerated: 40°C ± 2°C / 75 ± 5%RH)
Module-III (Drug Product): Firm has submitted data of drug product including its
description, composition, pharmaceutical development,
manufacture, manufacturing process and process control,
process validation protocols, control of excipients, control of
drug product, specifications, analytical procedures, validation
of analytical procedures, batch analysis, justification of
specifications, reference standard or materials, container
closure system and Stability.
Analytical method Firm has submitted analytical method validation studies for
validation/verification of product the applied product.
Container closure system Vial: Type I glass (European Ph. <3.2.1.>).
Stopper: Bromobutyl rubber elastomer Type I (European Ph.
<3.2.9.>).
Coloured aluminium protective cap.
Stability data of Drug Product The firm has submitted stability study data of 3 batches under
following conditions:
Accelerated, 6 months, 40°C ± 2°C/ 75%±5%RH
Intermediate, 36 months, 30°C ± 2°C/ 65%±5%RH

Batch no. Batch size Mfg. date

110501 42 L (Pilot batch) Dec. 2011
110502 350 L (Ind. Batch) Dec. 2011
110503 350 L (Ind. Batch) Dec. 2011

Remarks  The firm has claimed Ph. Eur. Specifications while the
product is available in British Pharmacopoeia.
Decision: The case was discussed in 331st meeting and deferred for clarification regarding finish
product specification. No response received from the firm. Registration Board again deferred the case
for clarification of finished product specifications (as the product is available in British Pharmacopoeia,
while the firm requested for Ph. Eur. Specification) and role of marketed by. As it is mentioned on
Form-5 that the product is marketed by Merilios Global Private Ltd. 16th Floor, Hoechst House,
Nariman Point, Mumbai- 400-021, Maharashtra, India.
7. Name, address of Applicant / M/s Himmel Pharmaceuticals (Pvt.) Ltd.
Importer Ground Floor,6- Judicial Colony Phase-I (Ext.) Shahrah Nazaria
e Pakistan, Lahore
Details of Drug Sale License of License No: 05-352-0065-016174-D
importer Address: Ground Floor,6- Judicial Colony Phase-I (Ext.)
Shahrah Nazaria e Pakistan, Lahore
Address of Godown: NA
Validity: 06. Feb. 2024
Status: License to sell drugs as distributor
Name and address of marketing M/s BEACON Pharmaceuticals Limited
authorization holder (abroad) Plant address: Kathali, Bhaluka, Mymensingh Bangladesh.
Name, address of manufacturer(s) M/s BEACON Pharmaceuticals Limited
Plant address: Kathali, Bhaluka, Mymensingh Bangladesh.
Name of exporting country Bangladesh
Detail of certificates attached (CoPP, CoPP: Original legalized CoPP (No. DA/ 6-110/ 2016/ 13526)
Free sale certificate, GMP dated 19-07-2023 valid upto 19-07-2025 issued by Government
certificate) of the people’s republic of Bangladesh, Ministry of Health &
Family welfare, Directorate General of Drug Administration,

Minutes of 332nd meeting of Registration Board (05th December, 2023) | 20

 Oushad Bhaban, Mohkhali Dhaka-1212, and Bangladesh. The
certificate confirms free sale status of the product in the country
of origin as well as GMP status.
GMP: Copy of GMP certificate No. DA/ 6-110/ 06/ 6751 dated;
23.03.2023 issued by M/s Beacon Pharmaceuticals Limited.
Details of letter of authorization / Firm has submitted copy of letter of authorization certificate
sole agency agreement from Beacon Pharmaceuticals limited. The letter specifies that
the manufacturer appoints M/s Himmel Pharmaceuticals Pvt.
Ltd. to register their products in Pakistan.
Status of the applicant ☐ Manufacturer
☒ Importer
☐ Is involved in none of the above (contract giver)
Status of application ☐ New Drug Product (NDP)
☒ Generic Drug Product (GDP)
Intended use of pharmaceutical ☒ Domestic sale
product ☐ Export sale
☐ Domestic and Export sales
For imported products, specify one ☒ Finished Pharmaceutical product import
the these ☐ Bulk import and local repackaging
☐ Bulk import and local repackaging for export purpose only
Dy. No. and date of submission Dy. No. 325 ; Dated: 06-09-2023
Details of fee submitted PKR. 150,000/- Dated: 16-08-2023
The proposed proprietary name / Heparon Injection
brand name
Strength / concentration of drug of Each 5ml contains:
Active Pharmaceutical ingredient Heparin Sodium……….25000 IU
(API) per unit
Pharmaceutical form of applied drug Liquid Injection
Pharmacotherapeutic Group of (API) Anti-coagulant
Reference to Finished product BP Specifications
specifications
Proposed Pack size 1’s
Proposed unit price As per SRO
The status in reference regulatory Heparin sodium 25,000 I.U./ml solution for injection
authorities (Wockhardt UK Ltd, UK)
For generic drugs (me-too status) PINE 5000 IU/5ml injection (Heparin sodium) by; HSC
Module-II (Quality Overall Firm has submitted QOS as per WHO QOS-PD template. Firm
Summary) has summarized information related to nomenclature, structure,
general properties, solubilities, physical form, manufacturers,
description of manufacturing process and controls, impurities,
specifications, analytical procedures and its validation, batch
analysis and justification of specification, reference standard,
container closure system and stability studies of drug substance.
Name, address of drug substance Suzhou Erye Pharma Co., Ltd. No. 2 Anmin Road Dongqiao
manufacturer Huangtai Town, Xiangcheng District, Suzhou City, Jiangsu,
P.R. China
Module-III Drug Substance: Firm has submitted detailed drug substance data for both sources
related to nomenclature, structure, general properties,
solubilities, physical form, manufacturers, description of
manufacturing process and controls, impurities, specifications,
analytical procedures.
Minutes of 332nd meeting of Registration Board (05th December, 2023) | 21
 Stability Studies of Drug Substance Firm has submitted stability study data of 3 batches at long term
(Conditions & duration of Stability conditions at 25℃ ± 2℃ / 60% RH ± 5% RH for 18 months.
studies) The accelerated stability data is conducted at 40°C±2℃ /
60%±5%RH for 06 months for accelerated conditions.
Module-III Drug Product: Firm has submitted data of drug product including its
description, composition, pharmaceutical development,
manufacture, manufacturing process and process control,
process validation protocols, control of excipients, control of
drug product, specifications, analytical procedures, validation of
analytical procedures, batch analysis, justification of
specifications, reference standard or materials, container closure
system and stability.
Analytical method Firm has submitted analytical method validation studies for the
validation/verification of product applied product.
Container closure system of the drug 5 ml clear glass Vial, 20 mm Rubber Stopper, 20 mm Flip off
product seal with ash color top.
Stability study data of drug product, Firm has submitted stability study data of 3 batches.
shelf life and storage conditions Accelerated stability studies have been conducted at 40°C±2°C
and 75%±5% RH for 6 months.
Real time stability studies conducted at 30°C ±2°C and 75% ±
5% for 36 months.
2460054
2460055
2460056
Remarks of Evaluator Non- clinical and Clinical trial data are not submitted by the
firm. Registration Board in its 271st meeting considered that
Heparin Sodium Injection is non-rDNA pharmacopoeial product
hence, revised its decision of 260th meeting and granted the
approvals on the basis of valid legalized CoPP & availability in
country of origin.
The firm has claimed BP specifications however, the test of Zone
electrophoresis has not been performed for Identification.
Previous Decision: Deferred for submission of analytical procedure indicating test of Zone electrophoresis
for identification of the product as per British Pharmacopoeia (M-331).
Evaluation by BE&R: The firm has submitted analytical method validation protocol and report for
identification of Heparin sodium in Heparon 25000 IU/5ml injection by Zone Electrophoresis.
Decision: On the basis of documents/information/data along with legalized CoPP indicating product
availability in the country of origin, Registration Board after detailed deliberation approved
the product subject to compliance to current Import Policy for finished drugs and provision
of legalized GMP certificate from drug substance manufacturer.
8. Name, address of Applicant / M/s Safemed Technologies,
Importer APT, 3, 2nd Floor, Retoon Plaza, Mini Market, Sector G-15/1,
Islamabad.
Details of Drug Sale License of License No: DHO-ISB-333
importer Address:
APT, 3, 2nd Floor, Retoon Plaza, Mini Market, Sector G-15/1,
Islamabad.
Validity: 24-08-2024
Status: Distribution License
Name and address of marketing M/s Hebei Changshan Biochemical Pharmaceutical Co. Ltd.,
authorization holder (abroad) No. 71 Menglong Street, South District of Zhengding High-tech
Industrial Development Zone, Zhengding Area of China (Hebei)
Pilot Free Trade Zone (050800), China
Name, address of manufacturer(s) M/s Hebei Changshan Biochemical Pharmaceutical Co. Ltd.,

Minutes of 332nd meeting of Registration Board (05th December, 2023) | 22

 No. 71 Menglong Street, South District of Zhengding High-tech
Industrial Development Zone, Zhengding Area of China (Hebei)
Pilot Free Trade Zone (050800), China
Name of exporting country China
Detail of certificates attached (CoPP, Firm has submitted legalized CoPP (No. Hebei 20210440) dated
Free sale certificate, GMP 15-10-2021 valid till 14-10-2023 issued by Hebei Province Drug
certificate) Administration. The certificate specifies the GMP status of the
manufacturer. The certificate specifies the Free Sale status of the
product in country of origin.
Details of letter of authorization / Firm has submitted product specific Letter of Authorization
sole agency agreement from Enterprise Legal Person of M/s Hebei Changshan
Biochemical Pharmaceutical Co., Ltd., According to the letter,
the firm M/s Hebei Changshan exclusively authorizes “Safemed
Technologies” to register, sale and quote the product. The letter
was issued on 06-04-2022 and valid till 30-03-2025.
Status of the applicant ☐ Manufacturer
☒ Importer
☐ Is involved in none of the above (contract giver)
Status of application ☐ New Drug Product (NDP)
☒ Generic Drug Product (GDP)
Intended use of pharmaceutical ☒ Domestic sale
product ☐ Export sale
☐ Domestic and Export sales
For imported products, specify one ☒ Finished Pharmaceutical product import
the these ☐ Bulk import and local repackaging
☐ Bulk import and local repackaging for export purpose only
Dy. No. and date of submission Dy. No. 14234 (R&I) Dated 13-06-2022
Details of fee submitted Rs. 150,000/- dated 02-06-2022
The proposed proprietary name / Metaparin Injection
brand name
Strength / concentration of drug of Each vial (5ml) contains:
Active Pharmaceutical ingredient Heparin Sodium……………25000IU
(API) per unit
Dosage form of applied drug Injection
Pharmacotherapeutic Group of (API) Anticoagulant
Reference to Finished product BP Specifications
specifications
Proposed Pack size 5’s Vials
Proposed unit price Rs. 1600/Vial
Shelf Life 03 Years
Storage Conditions 25±2℃/60±5% RH
The status in reference regulatory Heparin Panpharma of M/s Panpharma, France.
authorities
For generic drugs (me-too status) Vaxcel Heparin Sodium Injection of M/s Ghazali Brothers (Reg.
No. 088528).
Module-II (Quality Overall Firm has submitted QOS. Firm has summarized information
Summary) related to nomenclature, structure, general properties,
solubilities, physical form, manufacturers, description of
manufacturing process and controls, impurities, specifications,
analytical procedures and its validation, batch analysis and
Minutes of 332nd meeting of Registration Board (05th December, 2023) | 23
 justification of specification, reference standard, container
closure system and stability studies of drug substance and drug
product. The firm has also submitted the non-clinical and
clinical overviews and summaries.
Name, address of drug substance M/s Hebei Changshan Biochemical Pharmaceutical Co. Ltd.,
manufacturer No. 71 Menglong Street, South District of Zhengding High-tech
Industrial Development Zone, Zhengding Area of China (Hebei)
Pilot Free Trade Zone (050800), China
Module-III Drug Substance: Firm has submitted detailed drug substance data related to
nomenclature, structure, general properties, solubilities,
physical form, manufacturers, description of manufacturing
process, Characterization, impurities, specifications, analytical
procedures and its validation, batch analysis and justification of
specification, reference standard, container closure system and
stability studies of drug substance.
Stability Studies of Drug Substance Firm has submitted stability study data of 3 batches of Drug
(Conditions & duration of Stability Substance at real time conditions for 36 months and accelerated
studies) conditions for 06 months. The real time stability data conducted
at 250C±20C/60±5%RH.
Module-III Drug Product: Firm has submitted data of drug product including its
description, composition, pharmaceutical development,
manufacture, manufacturing process and process control,
process validation protocols, control of excipients, control of
drug product, specifications, analytical procedures, validation of
analytical procedures, batch analysis, justification of
specifications, reference standard or materials, container closure
system and stability.
Analytical method Firm has submitted validation of Analytical methods of Anti-
validation/verification of product factor IIa Activity, Anti-factor Xa activity, Benzyl Alcohol
determination & Sterility test.
Firm has submitted verification of Analytical methods of
Related substances & Bacterial Endotoxin test.
Container closure system of the drug EP Type I Colorless Glass vial, Grey Halogenated Butyl Rubber
product stopper, Aluminum & Plastic combined caps.
Stability study data of drug product Firm has submitted stability study data of 03 batches. The
accelerated stability study data is conducted at
40±2°C/75%RH±5% for 6 months. The real time stability study
data is conducted at 25±2°C/60%±5RH for 36 months.
Remarks of Evaluator Non- clinical and Clinical trial data are not submitted by the
firm. Registration Board in its 271st meeting considered that
Heparin Sodium Injection is non-rDNA pharmacopoeial
product, hence, revised its decision of 260th meeting and granted
the approvals on the basis of valid legalized CoPP & availability
in country of origin.
Previous Decision: Keeping in view the availability of product in country of origin as per submitted CoPP
and Heparin Injection being non-rDNA pharmacopoeial product; Registration Board approved the product as
per current Import Policy for finished drugs (M-320).
Evaluation by BE&R: Initially, the applied product was considered and approved in 320th meeting of
Registration Board. After that, the panel comprising of Mr. Muhammad Kashif and Mr. Faisal Shehzad
conducted virtual GMP inspection on 10-04-2023 & 11-04-2023 and concluded as following:

“Based on the proceedings of virtual inspection, documents reviewed and videos of the unit seen,
and considering the fact that Heparin sodium is a polysaccharide (no killed/attenuated
organism in final product), the panel has concluded that the firm has adequate systems to
manufacture heparin sodium and appeared to comply with the cGMP requirements. However,
the panel also observed during virtual inspection documentary review that the manufacturer

Minutes of 332nd meeting of Registration Board (05th December, 2023) | 24

 does not hold CoPP for applied strength of 25000 IU in China. Hence, the panel
recommended that the provisions under DRAP Act, 2012 and relevant rules must be checked
for grant of registration for such biological drugs. The importing firm may also be directed to
update DRAP for inclusion of manufacturing of any other biological drug in bulk production
and / or filling area by the manufacturer along with their NRA approval, QRM report and re-
validation of cleaning, if added in future.”

During further processing of the case, it was observed that the product is not licensed to be placed on the
market for use in China. Recently, the firm has submitted that our product is manufactured under license of
Ministry of Health of China. The product is also being exported and registered with health authorities of
Republic of the Philippines, Uzbekistan and Bolivia. Copies of registration certificates for these countries
have been provided.
Decision: Registration Board deferred the case for evidence of availability of product in the country of
origin or in RRA or in any three eastern European countries from same manufacturer.
9. Name, address of Applicant / Importer M/s PAK CHINA INTERNATIONAL,
498-C Feroz Shah Mehta Road, Karachi.
Details of Drug Sale License of importer License No: 0117
Address: 498-D Hume Road, Quaideen Colony, Near 3
Star Hall, Jamshed Road, Karachi
Validity: 18-04-2023.
Name and address of M/s Cisen Pharmaceutical Co. Ltd.,
marketing authorization Tongji Tech Industry Garden, Jining High and New
holder (abroad) Technology Industries Development Zone, Jining,
Shandong Province, P.R. China.
Name, address of M/s Cisen Pharmaceutical Co. Ltd.,
manufacturer(s) Tongji Tech Industry Garden, Jining High and New
Technology Industries Development Zone, Jining,
Shandong Province, P.R. China.
Name of exporting country China
Detail of certificates attached (CoPP, Free CoPP:
Sale certificate, GMP certificate) The firm has submitted original, legalized CoPP
(Shandong2036072) issued by Shandong Provincial
Medical Products Administration. The certificate
confirm that the product is actually on the market in the
exporting country and facilities and operations conform
to GMP as recommended by WHO.
The certificate is valid till 03-12-2024.
Details of letter of authorization / sole Copy of product specific sole agency agreement from
agency agreement manufacturer abroad hereby authorizes M/s Pak China
International, Karachi to act as authorized representative
to conduct all the formalities related to import, sell,
distribute in the territory of Pakistan.
Status of the applicant ☐Manufacturer
☒Importer
☐Is involved in none of the above (contract giver)
Status of application ☐New Drug Product (NDP)
☒Generic Drug Product (GDP)
Intended use of ☒ Domestic sale
pharmaceutical product ☐ Export sale
☐ Domestic and Export sales
For imported products, ☒ Finished Pharmaceutical product import
specify one the these ☐ Bulk import and local repackaging

Minutes of 332nd meeting of Registration Board (05th December, 2023) | 25

 ☐ Bulk import and local repackaging for export purpose
only
Dy. No. and date of submission Diary No. 804, Dated: 06-10-2023
Details of fee submitted Rs: 150,000/- Dated: 04-10-2023
Deposit Slip No. 640275156
The proposed proprietary name / brand name HEPARIN INJECTION 5ml/25000IU
Strength / concentration of drug of Active Each 5ml vial contains:
Pharmaceutical ingredient (API) per unit Heparin Sodium……………..25000 IU
Dosage form of applied drug Liquid Injection
Pharmacotherapeutic Group of (API) Anticoagulant
Finished product specifications BP specifications
Proposed Pack size 1 × 5 ml vial
Proposed unit price As per SRO
Shelf Life 24 months
Storage Conditions Store at 20°C – 25°C
Reference Regulatory Authorities Heparin sodium Injection, USFDA Approved.
For generic drugs (me-too status) PINE 5000 IU/5ml injection (Heparin sodium) by; HSC
Module-II (Quality Firm has submitted QOS as per WHO. Firm has
Overall Summary) summarized information related to nomenclature,
structure, general properties, manufacturers, description
of manufacturing process and controls, Characterization
(Elucidation of Structure and Other Characteristics),
impurities, specifications, analytical procedures, batch
analysis and justification of specification, reference
standard, container closure system and stability studies
of drug substance and drug product.
Name, address of drug substance M/s Dongying Tiandong Pharmaceutical Co Ltd.
manufacturer Address: No. 1236, Nan-er Road, Dongying City,
Shandong, P.R. China
Module-III Drug Firm has submitted detailed drug substance data related
Substance: to nomenclature, structure, general properties,
solubilities, physical form, manufacturers, description
of manufacturing process and controls, impurities,
specifications, analytical procedures and its validation,
batch analysis and justification of specification,
reference standard, container closure system and
stability studies of drug substance
Stability Studies of Drug Substance Firm has submitted stability study data of 3 batches at
long term conditions at 25℃ ± 2℃ / 60% RH ± 5% RH
for 18 months. The accelerated stability data is
conducted at 40°C±2℃ / 60%±5%RH for 06 months for
accelerated conditions.
Module-III Drug Product: Firm has submitted data of drug product including its
description, composition, pharmaceutical development,
manufacture, manufacturing process and process
control, process validation protocols, control of
excipients, control of drug product, specifications,
analytical procedures, validation of analytical
procedures, batch analysis, justification of
specifications, reference standard or materials, container
closure system and stability.

Minutes of 332nd meeting of Registration Board (05th December, 2023) | 26

 Analytical method Validation / verification of Firm has submitted the details of analytical method
the product validation.
Container closure system of the drug product 5ml vial low borosilicate glass tubing
Stability study data of Firm has submitted stability study data of 3 batches of
drug product, shelf life Heparin Injection at accelerated and real time
and storage conditions conditions.

The real time stability data conducted at 30°C ± 2°C /

65% RH ± 5%RH for 36 months and accelerated
stability data conducted at 40°C ± 2°C/75% RH ±
5%RH for 06 months for 3 batches.
170426
170427
170428
Remarks of Evaluator  Non- clinical and Clinical trial data are not submitted
by the firm. The same is not required as Registration
Board in its 271st meeting considered that Heparin
Sodium Injection is non-rDNA pharmacopoeial
product hence, revised its decision of 260th meeting
and granted the approvals on the basis of valid
legalized CoPP & availability in country of origin.
 The product was already registered with Pak china
International (Reg # 013266) dated 5th July 1992 with
same exporter as applied in the instant case i.e.Ningbo
Nuobai Pharmaceutical Co.,Ltd, China, However, the
firm did not submit the renewal application after 2007.
As per SRO when the renewal is submitted after the
lapse of one year of due date of submission of renewal
application, the product is automatically deregistered.
Therefore, the firm has submitted new application.
Previous Decision: Deferred for the clarification regarding the availability in the country of origin (M-331).
Decision: Registration Board deferred the case for evidence of availability of product in the country of
origin or in RRA or in three eastern European countries from same manufacturer.
10. Name, address of Applicant / Importer M/s AMB HK Enterprises (Pvt) Ltd.,
2nd Floor, Plaza 60, Commercial Block K, Phase-1
DHA, Lahore.
Godown address: House 27, Street 4-A Sanda Bhatian
Wala Gulshan Ravi, Lahore
Details of Drug Sale License of importer License No: 05-352-0058-104514D
Validity: 08-05-2028
Address of Godown: House 27, Street 4-A Sanda
Bhatian Wala Gulshan Ravi, Lahore
Status: License to sell drugs by way of whole sale.
Name and address of M/s Skymap Pharmaceuticals Pvt. Ltd.,
marketing authorization B-2 Dev Bhoomi Industrial Estate, Puhana Iqbalpur
holder (abroad) Road, Roorkee-247667 Distt. Haridwar Uttarakhand
India.
Name, address of M/s Skymap Pharmaceuticals Pvt. Ltd.,
manufacturer(s) B-2 Dev Bhoomi Industrial Estate, Puhana Iqbalpur
Road, Roorkee-247667 Distt. Haridwar Uttarakhand
India.
Name of exporting country India
Detail of certificates attached (CoPP, Free CoPP:
Sale certificate, GMP certificate) The firm has submitted copy of CoPP
(26/1/Drug/92/2019/19184) issued by Food Safety and
Drug Administration Authority, Directorate General of
Minutes of 332nd meeting of Registration Board (05th December, 2023) | 27
 Medical health & Family Welfare Uttarakhand, India.
The certificate confirm that the product is actually on the
market in the exporting country and facilities and
operations conform to GMP as recommended by WHO.
The certificate is valid till 07-06-2025.
Details of letter of authorization / sole Copy of sole agency agreement from manufacturer
agency agreement abroad hereby authorizes M/s AMB HK Enterprises Pvt
Ltd, Lahore to act as authorized representative to
conduct all the formalities related to import, sell,
distribute in the territory of Pakistan.
Status of the applicant ☐Manufacturer
☒Importer
☐Is involved in none of the above (contract giver)
Status of application ☐New Drug Product (NDP)
☒Generic Drug Product (GDP)
Intended use of ☒ Domestic sale
pharmaceutical product ☐ Export sale
☐ Domestic and Export sales
For imported products, ☒ Finished Pharmaceutical product import
specify one the these ☐ Bulk import and local repackaging
☐ Bulk import and local repackaging for export purpose
only
Dy. No. and date of submission Diary No. 17338, Dated: 11-07-2023
Details of fee submitted Rs: 150,000/- Dated: 10-07-2023
Deposit Slip No. 852401390
The proposed proprietary name / brand name Heparin Injection 5ml / 5000IU
Strength / concentration of drug of Active Each 5ml vial contains:
Pharmaceutical ingredient (API) per unit Heparin Sodium……………..5000 IU
Dosage form of applied drug Liquid Injection
Pharmacotherapeutic Group of (API) Anticoagulant
Finished product specifications BP specifications
Proposed Pack size 1 × 5 ml vial
Proposed unit price As per SRO
Shelf Life 24 months
Storage Conditions Store at a temperature not exceeding 30 °C.
Reference Regulatory Authorities Heparin sodium Injection, MHRA Approved.
For generic drugs (me-too status) Vaxcel Heparin Sodium Injection of M/s Ghazali
Brothers (Reg. No. 088528).
Module-II (Quality Firm has submitted QOS as per WHO. Firm has
Overall Summary) summarized information related to nomenclature,
structure, general properties, manufacturers, description
of manufacturing process and controls, Characterization
(Elucidation of Structure and Other Characteristics),
impurities, specifications, analytical procedures, batch
analysis and justification of specification, reference
standard, container closure system and stability studies
of drug substance and drug product.
Name, address of drug substance M/s Hebei Changshan Biochemical Pharmaceutical Co.,
manufacturer Ltd. No. 71, Menglong street, South District of

Minutes of 332nd meeting of Registration Board (05th December, 2023) | 28

 Zhengding High-Tech Industrial Development Zone,
Zhengding Area of China (Hebei) Pilot Free Trade Zone
P.R. China.
Module-III Drug Firm has submitted detailed drug substance data related
Substance: to nomenclature, structure, general properties,
solubilities, physical form, manufacturers, description
of manufacturing process and controls, impurities,
specifications, analytical procedures and its validation,
batch analysis and justification of specification,
reference standard, container closure system and
stability studies of drug substance
Stability Studies of Drug Substance Firm has submitted stability study data of 3 batches at
long term conditions at 25℃ ± 2℃ / 60% RH ± 5% RH
for 48 months. The accelerated stability data is
conducted at 40°C±2℃ / 60%±5%RH for 06 months for
accelerated conditions.
Module-III Drug Product: Firm has submitted data of drug product including its
description, composition, pharmaceutical development,
manufacture, manufacturing process and process
control, process validation protocols, control of
excipients, control of drug product, specifications,
analytical procedures, validation of analytical
procedures, batch analysis, justification of
specifications, reference standard or materials, container
closure system and stability.
Analytical method Validation / verification of Firm has submitted the details of analytical method
the product validation.
Container closure system of the drug product A colourless or straw coloured liquid free from turbidity
filled from turbidity filled in 5ml light amber colour,
tubular glass vials, plugged with 13mm bromo butyl
rubber stopper and sealed with 13 mm white flip off.
Stability study data of Firm has submitted stability study data of 3 batches of
drug product, shelf life Heparin Injection at accelerated and real time
and storage conditions conditions.

The real time stability data conducted at 30°C ± 2°C /

65% RH ± 5%RH for 24 months and accelerated
stability data conducted at 40°C ± 2°C/75% RH ±
5%RH for 06 months for 3 batches.
A20LV129
A20LV130
A20LV138
Remarks of Evaluator  Non- clinical and Clinical trial data are not submitted
by the firm. The same is not required as Registration
Board in its 271st meeting considered that Heparin
Sodium Injection is non-rDNA pharmacopoeial
product hence, revised its decision of 260th meeting
and granted the approvals on the basis of valid
legalized CoPP & availability in country of origin.
 Original, legalized CoPP issued by concerned
authority of country of origin is required to be
submitted.
 Original / notarized copy of sole agency agreement
are required to be submitted.
Decision: Deferred for submission of following:
 Legalized CoPP issued by concerned authority of country of origin.
 Original product specific sole agency agreement / Letter of Authorization.
Minutes of 332nd meeting of Registration Board (05th December, 2023) | 29
  Legalized GMP certificate of drug substance manufacturer.
11. Name, address of Applicant / Importer M/s AMB HK Enterprises (Pvt) Ltd.,
2nd Floor, Plaza 60, Commercial Block K, Phase-1
DHA, Lahore.
Godown address: House 27, Street 4-A Sanda Bhatian
Wala Gulshan Ravi, Lahore
Details of Drug Sale License of importer License No: 05-352-0058-104514D
Validity: 08-05-2028
Address of Godown: House 27, Street 4-A Sanda
Bhatian Wala Gulshan Ravi, Lahore
Status: License to sell drugs by way of whole sale.
Name and address of marketing authorization M/s Skymap Pharmaceuticals Pvt. Ltd.,
holder (abroad) B-2 Dev Bhoomi Industrial Estate, Puhana Iqbalpur
Road, Roorkee-247667 Distt. Haridwar Uttarakhand
India.
Name, address of M/s Skymap Pharmaceuticals Pvt. Ltd.,
manufacturer(s) B-2 Dev Bhoomi Industrial Estate, Puhana Iqbalpur
Road, Roorkee-247667 Distt. Haridwar Uttarakhand
India.
Name of exporting country India
Detail of certificates attached (CoPP, Free CoPP:
Sale certificate, GMP certificate) The firm has submitted copy of CoPP
(26/1/Drug/92/2019/19184) issued by Food Safety and
Drug Administration Authority, Directorate General of
Medical health & Family Welfare Uttarakhand, India.
The certificate confirm that the product is actually on the
market in the exporting country and facilities and
operations conform to GMP as recommended by WHO.
The certificate is valid till 07-06-2025.
Details of letter of authorization / sole Copy of sole agency agreement from manufacturer
agency agreement abroad hereby authorizes M/s AMB HK Enterprises Pvt
Ltd, Lahore to act as authorized representative to
conduct all the formalities related to import, sell,
distribute in the territory of Pakistan.
Status of the applicant ☐Manufacturer
☒Importer
☐Is involved in none of the above (contract giver)
Status of application ☐New Drug Product (NDP)
☒Generic Drug Product (GDP)
Intended use of ☒ Domestic sale
pharmaceutical product ☐ Export sale
☐ Domestic and Export sales
For imported products, ☒ Finished Pharmaceutical product import
specify one the these ☐ Bulk import and local repackaging
☐ Bulk import and local repackaging for export purpose
only
Dy. No. and date of submission Diary No. 17339, Dated: 11-07-2023
Details of fee submitted Rs: 150,000/- Dated: 10-07-2023
Deposit Slip No. 8120832213
The proposed proprietary name / brand name Heparin Plus Injection 5ml / 25,000IU
Strength / concentration of drug of Active Each 5ml vial contains:
Pharmaceutical ingredient (API) per unit Heparin Sodium……………..25000 IU

Minutes of 332nd meeting of Registration Board (05th December, 2023) | 30

 Dosage form of applied drug Liquid Injection
Pharmacotherapeutic Group of (API) Anticoagulant
Finished product specifications BP specifications
Proposed Pack size 1 × 5 ml vial
Proposed unit price As per SRO
Shelf Life 24 months
Storage Conditions Store at a temperature not exceeding 30 °C.
Reference Regulatory Authorities Heparin sodium Injection, USFDA Approved.
For generic drugs (me-too status) Vaxcel Heparin Sodium Injection of M/s Ghazali
Brothers (Reg. No. 088528).
Module-II (Quality Firm has submitted QOS as per WHO. Firm has
Overall Summary) summarized information related to nomenclature,
structure, general properties, manufacturers, description
of manufacturing process and controls, Characterization
(Elucidation of Structure and Other Characteristics),
impurities, specifications, analytical procedures, batch
analysis and justification of specification, reference
standard, container closure system and stability studies
of drug substance and drug product.
Name, address of drug substance M/s Hebei Changshan Biochemical Pharmaceutical Co.,
manufacturer Ltd. No. 71, Menglong street, South District of
Zhengding High-Tech Industrial Development Zone,
Zhengding Area of China (Hebei) Pilot Free Trade Zone
P.R. China.
Module-III Drug Firm has submitted detailed drug substance data related
Substance: to nomenclature, structure, general properties,
solubilities, physical form, manufacturers, description
of manufacturing process and controls, impurities,
specifications, analytical procedures and its validation,
batch analysis and justification of specification,
reference standard, container closure system and
stability studies of drug substance
Stability Studies of Drug Substance Firm has submitted stability study data of 3 batches at
long term conditions at 25℃ ± 2℃ / 60% RH ± 5% RH
for 48 months. The accelerated stability data is
conducted at 40°C±2℃ / 60%±5%RH for 06 months for
accelerated conditions.
Module-III Drug Product: Firm has submitted data of drug product including its
description, composition, pharmaceutical development,
manufacture, manufacturing process and process
control, process validation protocols, control of
excipients, control of drug product, specifications,
analytical procedures, validation of analytical
procedures, batch analysis, justification of
specifications, reference standard or materials, container
closure system and stability.
Analytical method Validation / verification of Firm has submitted the details of analytical method
the product validation.
Container closure system of the drug product A colourless or straw coloured liquid free from turbidity
filled from turbidity filled in 5ml light amber colour,
tubular glass vials, plugged with 13mm bromo butyl
rubber stopper and sealed with 13 mm white flip off.

Minutes of 332nd meeting of Registration Board (05th December, 2023) | 31

 Stability study data of Firm has submitted stability study data of 3 batches of
drug product, shelf life Heparin Injection at accelerated and real time
and storage conditions conditions.

The real time stability data conducted at 30°C ± 2°C /

65% RH ± 5%RH for 24 months and accelerated
stability data conducted at 40°C ± 2°C/75% RH ±
5%RH for 06 months for 3 batches.
A20LV141
A20LV142
A21LV032
Remarks of Evaluator  Non- clinical and Clinical trial data are not submitted
by the firm. The same is not required as Registration
Board in its 271st meeting considered that Heparin
Sodium Injection is non-rDNA pharmacopoeial
product hence, revised its decision of 260th meeting
and granted the approvals on the basis of valid
legalized CoPP & availability in country of origin.
 Original, legalized CoPP issued by concerned
authority of country of origin is required to be
submitted.
 Original / notarized copy of sole agency agreement
are required to be submitted.
Decision: Deferred for submission of following:
 Legalized CoPP issued by concerned authority of country of origin.
 Original product specific sole agency agreement / Letter of Authorization.
 Legalized GMP certificate of drug substance manufacturer.
12. Name, address of Applicant / Importer M/s We Care
Address: Flat B-6 Block 12 D 2nd Floor G-8 Markaz
Islamabad Pakistan.
Details of Drug Sale License of License No: DHO-ISB-930
importer Address: Flat B-6 Block 12 D 2nd Floor G-8 Markaz
Islamabad Pakistan
Validity: 19-06-2025
Status: License to sell drugs as distributor
Name and address of marketing M/s PT PRATAPA NIRMALA
authorization holder (abroad) JL. INDUSTRI VI TANGERANG 15135-INDONESIA
Name, address of manufacturer(s) M/s PT PRATAPA NIRMALA
JL. INDUSTRI VI TANGERANG 15135-INDONESIA
Name of exporting country Indonesia
Detail of certificates attached (CoPP, Firm has submitted legalized CoPP
Free sale certificate, GMP certificate) (No.RG.01.05.32.321.05.22.3865) dated 17-05-2022
valid till 17-05-2024 issued by National Agency of Drug
and Food control Jl. Percetakan Negara No. 23,
JAKARTA- INDONESIA. The certificate specifies the
GMP status of the manufacturer. The certificate specifies
the Free Sale status of 5’s x 5ml vial in country of origin.
Details of letter of authorization / sole Firm has submitted legalized LOA dated 26-04-2022 and
agency agreement legalized distribution agreement dated 21-04-2022 (signed
by both firms) valid for five years.
Status of the applicant ☐ Manufacturer
☒ Importer
☐ Is involved in none of the above (contract giver)
Status of application ☐ New Drug Product (NDP)
☒ Generic Drug Product (GDP)
Intended use of ☒ Domestic sale
pharmaceutical product ☐ Export sale

Minutes of 332nd meeting of Registration Board (05th December, 2023) | 32

 ☐ Domestic and Export sales
For imported products, specify one the ☒ Finished Pharmaceutical product import
these ☐ Bulk import and local repackaging
☐ Bulk import and local repackaging for export purpose
only
Dy. No. and date of submission Dy. No. 5109 (R&I) dated 21-02-2023
Details of fee submitted Deposit Slip # 8167115543 of PKR. 150,000/- dated 22-
02-2023
The proposed proprietary name / brand Inviclot Injection
name
Strength / concentration of drug of Each ml contains:
Active Pharmaceutical ingredient (API) Heparin Sodium……………5000IU
per unit
Dosage form of applied drug Liquid Injection
Pharmacotherapeutic Group of (API) Anticoagulant
Reference to Finished product -
specifications
Proposed Pack size 5’s x 5ml vial
Proposed unit price Not Provided
Shelf Life 24 months
Storage Conditions Store Below 30℃
The status in reference regulatory Not provided
authorities
For generic drugs (me-too status) Vaxcel Heparin Sodium Injection of M/s Ghazali Brothers
(Reg. No. 088528).
Module-II (Quality Firm has submitted QOS. Firm has summarized
Overall Summary) information related to nomenclature, structure, general
properties, solubilities, physical form, manufacturers, flow
of manufacturing process, analytical procedures,
justification of specification.
Name, address of drug substance Company: Adeste Indústria de Produtos Animais LTD
manufacturer Address:Rua Paes Leme, 524, 6º andar Grupo 63 - CEP
054 24 904 Pinheiros – São Paulo – Brazil Phone: 55 11
30975544 Fax: 55 11 30975545
Module-III Drug Firm has submitted drug substance data related to
Substance: nomenclature, structure, general properties, solubilities,
physical form, manufacturers, specifications, analytical
procedures, batch analysis and justification of
specifications.
Stability Studies of Drug Substance Firm has provided stability studies of 3 batches of drug
substance.
Module-III Drug Product: Firm has summarized data of drug product including its
composition, manufacturing process, control of drug
product, process verification, specifications, batch
analysis, container closure system and stability.
Analytical method Firm has submitted validation of Analytical methods
validation/verification of product
Container closure system of the drug Heparin Sodium 5000 units/mL is supplied as 5-mL
product volume injection, in a vial made of type I glass and packed
in a box. Each container bears printed information
concerning product characteristics (name, active
ingredient, pharmaceutical form, strength) and batch
characteristics (batch number and expiration date). The
suitability of the primary packaging is confirmed by the
Certificate of Quality from the vial manufacturer.
Incompatibilities with primary packaging or excipients
used were not observed; however, during the stability

Minutes of 332nd meeting of Registration Board (05th December, 2023) | 33

 study there were not any particles leaked and the
parameters tested remained within the requirements.
Stability study data of drug product Firm has submitted stability study data of 03 batches. The
accelerated stability studies are conducted at
40±2°C/75%RH±5% for 6 months. The real time stability
studies are conducted at 30±2oC/75%±5RH for 36 months
for one batch. While at 30±2oC/60%±5RH for other two
batches.
Bacterial Endotoxin test and sterility test are performed at
0,6,24 and 36 months in real time stability studies while at
0 and 6 months in accelerated stability studies.
Remarks of Evaluator The firm has not performed testing as per official
pharmacopeia.
Decision of RB in 331st meeting Registration Board deferred the case for submission of
specifications, analytical procedures and COAs as per
official pharmacopoeia.
Decision: The case was discussed in 331st meeting of Registration Board. No response received from
the firm. Case was deferred for clarification by the firm.

Imported Human Biological (GDK Flu Quadrivalent Vaccine) applied by M/s Lab Diagnostic Systems
(SMC) Pvt. Ltd.

13. Name, address of Applicant / Lab Diagnostic Systems (SMC) Pvt. Ltd.
Importer Plot 36-A, PSIC SIE, Taxila Rawalpindi
Details of Drug Sale License of importer License No: 01-374-0006-96845D
Address: 36-A, PSIC, SIE, Taxila Rawalpindi
Validity: 04/08/2024
Name and address of marketing Name: Jiangsu GDK Biological Technology Co., Ltd.
authorization holder (abroad) Address: No. 12, Yujin Road, Taizhou Pharmaceutical Hi
tech Industrial Development Zone, Jiangsu Province,
China
Name, address of manufacturer(s) Name: Jiangsu GDK Biotechnology Technology Co., Ltd.
Address: No. 12, Yujin Road, Taizhou Pharmaceutical Hi
tech Industrial Development Zone, Jiangsu Province,
China
Name of exporting country China
Detail of certificates attached (CoPP, Firm has submitted legalized CoPP (No.Jiangsu20230116)
Free Sale certificate, GMP issued by Jiangsu Medical Product Administration, China.
certificate) The COPP specifies that the product is licensed for sale in
country of origin. The COPP also specifies the GMP status
of manufacturer.
Details of letter of authorization / sole Firm has submitted legalized Distribution Certificate from
agency agreement M/s Jiangsu GDK Biological Technology Co., Ltd. China.
Status of the applicant ☐ Manufacturer
☒ Importer
☐ Is involved in none of the above (contract giver)
Status of application ☐ New Drug Product (NDP)
☒ Generic Drug Product (GDP)
Intended use of pharmaceutical product ☒ Domestic sale
☐ Export sale
☐ Domestic and Export sales
For imported products, specify one the ☒ Finished Pharmaceutical product import
these ☐ Bulk import and local repackaging
☐ Bulk import and local repackaging for export purpose
only
Dy. No. and date of submission Form -5F
Minutes of 332nd meeting of Registration Board (05th December, 2023) | 34
 Dy. No.: 478
R&I dated: 13/09/2023
Details of fee submitted Rs: 150,000
Dated: 18/08/2023
Deposit Slip No. 9971882166
The proposed proprietary name / brand GDK Flu Quadrivalent Vaccine
name
Strength / concentration of drug of Each 0.5 mL dose contains 15 μg of hemagglutinin protein
Active (60 μg total) from each of the following four influenza
Pharmaceutical ingredient (API) per unit subtypes or lineages: A/H1N1, A/H3N2, B Victoria, B
Yamagata 0.5ml/piece/box.
Dosage form of applied drug Pre-Filled Syringe
Pharmacotherapeutic Group of (API) Quadrivalent influenza Vaccine
Reference to Finished product Chinese Pharmacopoeia
specifications
Proposed Pack size 1’s PFS
Proposed unit price As per SRO
Shelf Life 12 months
Storage Conditions 2°C – 8°C
The status in reference regulatory INFLUVAC® Tetra 2021 USFDA
authorities
For generic drugs (me-too status) -
Module-II (Quality Overall Summary Firm has submitted QOS as per ICH guidelines. Firm has
summarized information related to general properties,
manufacturers, description of manufacturing process and
controls, characterization, specifications analytical
procedures and its validation, batch analysis and
justification of specification, reference standard, container
closure system and stability studies of drug substance and
drug product. The firm has also submitted the non-clinical
and clinical overviews and summaries.
Name, address of drug substance Name: Jiangsu GDK Biological Technology Co., Ltd.
manufacturer Address: No. 12, Yujin Road, Taizhou, Jiangsu Province,
China
Module-III Drug Substance: Firm has submitted detailed drug substance data related to
nomenclature, structure, general properties, solubilities,
physical form, manufacturers description of manufacturing
process and controls, impurities, specifications, analytical
procedures and its validation, batch analysis, container
closure system.
Stability Studies of Drug Substance Firm has submitted stability data of 3 batches as;
(Conditions & Long term stability data (6±2oC) at 0,1,2,3,6,9,12 and 15
duration of Stability studies) months.
Stress testing (37±2oC) at 0,1,3,5,7,10,14, and 21 days.
Accelerated stability study (25±2oC) at 0,1,3,5,7,10,14 and
21 days.
Module-III Drug Product: Firm has submitted data of drug product including its
description,
composition, pharmaceutical development, manufacture,
manufacturing process and process control, process
validation protocols, control of excipients, control of drug
product, specifications, analytical procedures, validation of
analytical procedures, batch analysis, justification of
specifications, reference standard or materials, container
closure system and stability.
Analytical method validation Method verification was carried out for identification,
/verification of product osmotic pressure molar concentration, free formaldehyde
content, hemagglutinin content, protein content,
ovalbumin content, sterility test and bacterial endotoxin

Minutes of 332nd meeting of Registration Board (05th December, 2023) | 35

 test on applied vaccine. Chinese Pharmacopeia was
followed for specifications.
Container closure system of the drug The container closure system consists of primary
product packaging materials and secondary packaging materials.
The primary packaging materials include assemblages for
prefilled syringes (with stainless steel needles), chlorobutyl
rubber stoppers for prefilled syringes and plungers for
prefilled syringes; secondary packaging materials include
labels, package inserts, boxes, medium boxes, cartons,
PVC sheets, and composite films.
Stability study data of drug product, Firm has submitted stability study data of 3 batches at real
shelf life and storage conditions time and accelerated conditions. The real time stability data
provided is conducted at 6 ± 2 °C for 18 months. The
accelerated stability data provided is of 03 batches and is
conducted at 25 ± 2 °C for 06 months.
Module-IV (Non-Clinical) Firm has submitted;
Toxicity study in mice.
Active systemic anaphylaxis study in guinea pigs.
Muscle irritation study in rabbits.
Module-V (Clinical) Firm has submitted,
 A single center open label phase 1 clinical trial
investigating safety in 41 health individuals aged 18-
49 years old.
 A phase III clinical trial with single center,
randomized, double blind, positive controlled, non-
inferiority design investigating immunogenicity and
safety in volunteers over 3 years of age.
Remarks of Evaluator  The brand name on CoPP is different from the brand
name on Form5-F (CTD).
 Stability data submitted by the firm does not include
batch size, relative humidity and pack size.
 Repeat dose toxicity studies are not provided in detail
in Module 4 of CTD.
 Phase III clinical trial is monocentric.
Decision of RB in 331st meeting Registration Board after due deliberation decided to
defer the case for submission of following deficient
information/documents:
1) Repeat Dose Toxicity Studies,
2) Rationale/guideline for selection of monocentric phase
III clinical trial,
3) clarification of brand name and parameters of stability
data i.e batch size, relative humidity and pack size.
The matter of short availability of influenza vaccine in the
country was discussed in detail and the board noted that in
order to make the product available in the country, more
competitors should come in market, the Board constituted
the following panel for virtual GMP inspection of
manufacturer abroad:
 Ms. Haleema Sharif (Deputy Director BE&R)
 Mr. Akbar Ali (Deputy Director QA&LT)
Remarks of BE&R The firm has submitted the following;
 Repeat dose toxicity studies
 Stability data with required parameters/conditions
 Clarification on brand name that the CoPP is with
Generic name and Form 5-F is with brand name and
Letter of Authorization from manufacturer is also
with brand name.
 The firm has submitted declaration from principal
that all the Chinese manufacturers of influenza
Minutes of 332nd meeting of Registration Board (05th December, 2023) | 36
 vaccine are conducting monocentric phase III clinical
trials.
The manufacturer has developed the product as per
“Chinese Pharmacopoeia” while the product monograph
is available in “European Pharmacopoeia”.
Decision: Keeping in view above; Registration Board after detailed deliberation, legalized CoPP
and availability of product in country of origin, approved the product subject to compliance of
specifications as per Drug Specification Rules 1978 and current Import Policy for finished drugs.

End of Document

Minutes of 332nd meeting of Registration Board (05th December, 2023) | 37