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Drug Regulatory Authority of Pakistan

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1. Lot Release

NCLB implements Lot release and Lab testing of Biological Drugs as per Schedule I of DRAP Act, 2012 (Act No. XXI of 2012)

and is part of DRAP Authority under Section 3 of this Act.

2020 is 20th year of service of NCLB

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Lot Release

Lot Release SOP for the importers and manufacturers of Biological drugs

for printing of LR Request form use the separate form

SOP No.                                             036/A-NCL-LRE-08

Title:                                       Procedure for Lot Release of Biological Products

Effective Date:                       January, 2020

Version:                                    08

Next Review date:                 December, 2021

 

Revised by:

Zafar Mahmood Minhas

Deputy Director,

National Control Laboratory for Biologicals Islamabad.

 

Approved/ Authorized  by:

Abdul Samad Khan

Director,

National Control Laboratory for Biologicals Islamabad.

 

 

Document History:

Version

Effective date

Significant Changes

Previous Version

00

Sep.2006

Initial version

-

01

Feb.2007

Revision after discussion with stake holder

00

02

Oct.2010

This version was developed to change the format of the SOPs to an improved form and style.

01

03

2013

After the 18th Amendment and devolution of Ministry of Health, in the header the word Ministry of Health has been replaced with the words Ministry of National Health Services, Regulations & Coordination, Drug Regulatory Authority of Pakistan and accordingly some changes are made in the text where applicable.

02

04

2015

Routine revision and following corrections. additions/deletions/changes were made: sop version no.,Sec.1.2,2.2,,3.1,3.2,4.2,.4.4,4.5,5.1.1,5.1.3,  5.1.4, 5.2.1,rearrangement of paragraphs for logical understanding of events, sec.2.4 for non application  of lot release system to the veterinary drugs, changes in some sections to make the sop in line with the DRAP Act 2012 and Sec. 5.3.3 added for clarification of field and lot release samples   

03

05

2017

Routine revision

04

06

2019

Routine revision

05

07

2019

Sub Sec. 5.4.4-5.4.7 added for LTR exemption and fast track release.

06

08

2020

Sub Sec. 3.3,5.1.2, 5.1.3, 5.2.2, 7.2 and 7.3 for inclusion of revised lot release request form.

07


1.      PURPOSE:

1.1.          The purpose of this SOP is to describe the method to obtain lot release certificate from National Control Laboratory for Biologicals for release of the Drugs into the market.

1.2.          Lot release of biological products is performed within the framework of section 14 of the Drugs Act 1976 (XXXI of 1976) and Schedule I of the DRAP Act 2012

           by National Control Laboratory for Biologicals.

1.3            The schedule I of DRAP Act 2012 shall apply for the definition of  Lot Release and of the Biological Drugs( Please see section 2.4).

1.4            Lot release and field sample clarification is given in section 5.3.3

2.      SCOPE:

2.1.          Verification that the Biological Drugs, whether imported or locally manufactured are in conformity with the approved specifications i.e. they conform the Drugs (Specifications) Rules, 1978 and DRAP Act, 2012.

2.2.          This applies to all the Biological Drugs as described under rule 2 (bd) of The Drugs (Licensing, Registering & Advertising) Rules 1976, whether imported or locally manufactured. Added as per SRO 779(1) / 2000 dated 5th November 2001 (Please see section 2-4 for Veterinary Biological Drugs) and as per schedule I of the DRAP Act, 2012.

2.3.          The approved specifications are to be used as a reference for the evaluation of each lot submitted for lot release. The updated relevant product dossier must be available for ready reference in the Library of NCLB.

2.4.          The present SOP is related to the release of Biological Drugs meant for human use and is based on W.H.O. recommendations (TRS 978, Annex 2; 2013), it is not meant and is not applicable to veterinary biological drugs that are manufactured and controlled under OIE guidelines

3.      RESPONSIBILITIES:

3.1.          It is the responsibility of the Importers and/or manufacturers to follow this procedure described in this SOP while submitting the request for lot release of already registered Biological Drug.

3.2.          Authorized officer (Officer notified by the Federal Government for the release of imported biological products) is responsible for ensuring that this procedure is being followed.

3.3.          Director / Federal Government Analyst, National Control Laboratory for Biologicals, is responsible to issue lot release certificate on the prescribed form (Controlled Document-003.1).

4.      REQUIREMENTS:

4.1.          Summary protocols of each lot. (Summary Protocol: A document summarizing all manufacturing steps and tests performed along with results for that particular lot of vaccines, sera and interferon, which is certified and signed by the authorized person of the manufacturing company).

4.2.          Lot release certificate from NRA (National Regulatory Authority) of exporting country (for imported finished dosage form of biological drugs only) or exemption certificate in case the lot release does not apply to the imported biological drugs in the country of origin.

4.3.          Batch Production Record (BPR) of the particular lot (for locally manufactured products).

4.4.          Lot release fee for each lot as specified by National Control Laboratory for Biologicals. The Lot release fee may be revised from time to time as the National Control Laboratory for Biologicals deems necessary with the approval of the Policy Board of the DRAP (Annex-4).

4.5.          Copy of the paid challan and invoice

4.6.          Samples of each lot in quantity as specified by National Control Laboratory for Biologicals. The quantity may be revised from time to time as the National Control Laboratory for Biologicals deems necessary. (Annex-1).

5.      PROCEDURE:

5.1.          Imported Biological Drugs:

5.1.1.         Upon arrival of the shipment/consignment the importer applies for the grant of provisional release of the consignment. The authorized officer (Officer notified by the Federal Government for the release of imported biological products) at the port of entry, who grants provisional release of the consignment, this is to take the consignment from port to importer’s warehouse cold room for proper storage, within a time period not exceeding two working days, with the direction to obtain lot release certificate from National Control Laboratory for Biologicals before release of the biological drug into the market.

5.1.2.         Upon receiving the consignment the importer applies for the lot release of each lot / batch, within a week, directly to National Control Laboratory for Biologicals to obtain lot release certificate, on prescribed form (Controlled Document-001.1) and sends the specified quantity of samples of each lot / batch if required with in a week to the National Control Laboratory for Biologicals along with the documents and lot release fee as described in section 4.

5.1.3.         Upon receiving the request for issuance of lot release certificate, the National Control Laboratory for Biologicals will apply the prescribed procedure applicable to each biological drug and issue a certificate on prescribed form (Controlled Document-003.1), within a time frame ranging from two weeks to eight weeks depending upon the assessment applicable, as per WHO recommendations.

5.1.4.         Upon receiving the lot release certificate from National Control Laboratory for Biologicals the importer submits it to the authorized officer (Officer notified by the Federal Government for the release of imported biological drug at the port of entry) to get permission for the sale of the biological drug accordingly.

5.1.5.         The authorized officer (Officer notified by the Federal Government for the release of imported biological products) will grant permission to the importer, within two working days of receipt of lot release certificate, to place the product on the market for use.

5.2.          LOCALLY MANUFACTURED BIOLOGICAL PRODUCTS:

5.2.1.         Upon completion of manufacturing process and quality control testing and quality assurance review of each lot, the manufacturer sends the sample of each lot/batch, within a week, directly to National Control Laboratory for Biologicals to obtain lot release certificate, on prescribed form (Controlled Document-003) in quantity specified by National Control Laboratory for Biologicals along with the documents and lot release fee as described in section 4.

5.2.2.         Upon receiving the request for issuance of lot release certificate, the National Control Laboratory for Biologicals will issue a certificate on prescribed form (Controlled Document-003.1) within a time frame ranging from two weeks to eight weeks depending upon the assessment applicable, as per WHO recommendations for that particular biological drug.

5.2.3.         As per schedule I of the DRAP Act 2012, the companies are to clearly specify in the BPRs which type of biological drugs they are manufacturing

5.3.          SAMPLING:

5.3.1.         Representative samples of each lot are collected by importer and/or manufacturer, in quantity specified by National Control Laboratory for Biologicals.

5.3.2.         Samples are to be provided in their approved commercial packing in which the drug is to be marketed or supplied to the government and are to be from the lot that is being applied for lot release and Sample containers are properly sealed and marked by name, signature and stamp of the authorized person (the person authorized by the importer/ manufacturer for the said purpose) with date of sampling.

5.3.3.         Suppliers are encouraged to ensure the physical inspection of their government supplies to be conducted by the concerned government stores department. It is the responsibility of the suppliers and concerned government departments to ensure the implementation of SOP for cold chain management and to ensure physical inspection; Lot Release Certificate is neither a substitute of a complete physical inspection of stores to be conducted by government departments nor is to be used in court proceedings for field samples. Field samples are to be picked up by the relevant FID or PDI as per approved and notified procedure under DRAP Act, 2012 and Drugs Act, 1976 and  are to be retested by NCLB, only these reports could be produced in the Court. The passing of a lot and the testing of the field sample are two different procedures, they should not be confused. A field or market samples of a passed lot may fail due to a number of reasons that need to be investigated on scientific lines.

5.3.4.         Sealed samples are sent to the Director / FGA, National Control Laboratory for Biologicals, on prescribed form along with the requirements as described in section 4 at the postal address given below:

The Director/ Federal Government Analyst,

National Control Laboratory for Biologicals,

Prime Minister National Health Complex Chak Shehzad Park Road, Islamabad.

5.3.5.         The samples should be sent in accordance with the  temperature                         requirements of the biological drugs.

5.4.          GUIDENCE FOR INDUSTRY

5.4.1.         Lot release is applicable to every batch/lot in a shipment which means If there are one or more batches/lots, lot release will be applicable to each and every batch separately, for which separate fee shall be deposited.

5.4.2.         If same batch is imported again in a different shipment, again the lot release will be applied and lot release fee will be deposited.

5.4.3.         Fee Schedule will be according to SRO 461 (I) / 2013 dated 30-05-2013 and annex.4 of the SOP.

5.4.4.         For the imported biologicals originating from other countries as a result of a pandemic or in response to an emergency such as epidemic or disaster as defined in WHO Document for Disaster Management, sampling and testing shall not be applicable at the import stage.

5.4.5.         The pandemic vaccine of Avian Influenza shall have the special status that it shall require extreme speed in clearing due to the exigency of matter of immunization required for saving the available lives. Advance clearance or lot release may be issued in all such cases where speed is of utmost significance in pandemics. The required formulation in these cases cannot be predefined due to the nature of the virus; hence the WHO Website data and local Avian Influenza Programme officials may be contacted for information gathering. No sample testing of the vaccine shall be done in these cases at the import level; however representative samples may be kept for reference purposes in NCLB.

5.4.6.         In the situations of exigency like Earthquakes, floods, natural disasters,   pandemics, major epidemics and war etc. in the public interest, laboratory has the provision for exemption from lot release and this is in the pretext of SRO 779(I)/2000, dated 5th November 2001 that permits this exemption

5.4.7.         NCLB also have a mechanism for fast track release of the biological products in cases of an emergency such as Earthquakes, floods, natural disasters,   pandemics, major epidemics and war etc., in the larger public interest. In these cases products are released out of que on top priority basis. However the manufacturers/importers are bound to fulfill the requirements mentioned earlier in the SOP.

6.      APPEALS AGAINST DECISION OF NATIONAL CONTROL LABORATORY FOR BIOLOGICALS:

6.1.          In case of the final rejection of the request for release of a lot / batch of biological drug the aggrieved party may file an appeal against the decision of the National Control Laboratory for Biologicals as per procedure described under section 22 of the Drugs Act 1976.

7.      REFERENCE DOCUMENTS:

7.1.          Annex-1: Quantity of samples.

7.2.          Controlled Document-001.1: Lot release request form.

7.3.          Controlled Document-003.1: Lot release certificate.

7.4.          Annex-4:  Schedule of lot release Fees.

8.      Change Control History:

Annex-1

Quantity of vaccines, sera & interferon required for the issuance of lot release certificate.

 

Product

Quantity (vials/unit packs)

Imported*

Locally Manufactured

Tetanus Toxoid.

§  0.5 ml

§  5.0 ml

 

25

05

 

80

30

Anti Tetanus Sera.

§  1.0 ml

§  3.0 ml

§  5.0 ml

 

10

05

05

 

40

30

30

Oral Polio Vaccine.

§  5.0 ml

 

05

 

40

Measles Vaccine.

§  5.0 ml

 

05

 

40

Rabies Vaccines.

§  0.5 ml

 

20

 

80

Hepatitis-B Vaccine.

§  0.5 ml

§  1.0 ml

§  5.0 ml

 

15

10

05

 

40

30

30

Snake Venom Anti Sera.

§  5.0 ml

§  10.0 ml

 

05

05

 

40

30

Interferon

05

40

             Note: The lot release certificate for biological drugs other than mentioned in above list will be issued on the basis of summary protocol review only, due to non availability of testing facility at present. Therefore the request for the release of such products is required to be accompanied by summary protocol, lot release certificate from NRA (National Regulatory Authority) of exporting country and samples in quantity 02 vials/unit packs for physical examination and verification of labeling requirements as per Drugs Act 1976 and Rules framed there under.

 * The quantity of samples for imported products is based on minimum requirement to carry out the most essential tests and applies only to those products which are accompanied by lot release certificate from NRA (National Regulatory Authority) of exporting country. The request for the release of imported products, accompanied by exemption certificate from NRA (National Regulatory Authority) of exporting country, will be subjected to full range of testing and requirements (lot release fee and quantity of samples) applicable to locally manufactured Biological drugs.


 

 

Controlled Document-001.1

 

 

 

(For Official se only)

 

L.R No.

 

 

Date of Receipt

 

 

 

 

 

Lot Release Request Form

 

The Director / Federal Government Analyst,                    Reference No. _________________ 

National Control Laboratory for Biologicals,                    Dated:             ________________________

Drug Regulatory Authority of Pakistan,

Ministry of National Health Services, Regulations and Coordination,

Prime Minister’s National Health Complex,

Park Road, Chak Shahzad,

Islamabad.

 

            Please issue the lot release certificate in respect of the biological product as detailed below. All the required documents are enclosed along with. The sample of the product will be provided if required:-

 

Importer/ Manufacturer Details

 

Name  and address of the Importer/manufacturer

 

 

 

 

Commercial Invoice No.

 

Invoice Date

 

Date of Receipt of Shipment

 

Date of Endorsement of Invoice

 

Mode of Shipment

 

Port of Receipt of Shipment

 

Name and Address of the Indent Holder (if applicable)

 

Product details

 

Name of Product

 

 

Generic Name of Product

 

 

Registration No.

 

 

Lot No.

 

 

Manufacturing Date (dd/mm/yyyy)

 

 

Expiry Date (dd/mm/yyyy)

 

 

Storage Temp

 

 

Transportation Temp.

 

 

Name and address of Manufacturer

 

 

Pharmaceutical form

 

 

Type of Container

 

 

Number of Doses per container

 

 

Volume per container

 

 

Strength

 

 

 

Solvent/ Diluent Details (in case of Freeze Dried Product)

 

Solvent/ Diluent Name

 

Lot No.

 

Type of container

 

Volume per container

 

Registration No.

 

Mfg. Date

 

Exp. Date

 

Name & address of Manufacturer

 

Details of Fee Deposited 

 

Bank Name 

 

Bank Code

 

Deposit Date

 

Deposit Slip No.

 

Amount Deposited 

 

Endorsement from DRAP

□ Yes

Lot Release Requested By Authorized Person

 

Name

 

Designation

 

Signature

 

Date

 

Telephone No.

 

Cell No.

 

Name of Firm/ Pharmaceutical Company

 

Complete Address

 

Official Stamp

 

 

 


For Official Use only:

1.

Summary Protocol Received

□ Yes

 

2.

Lot release certificate from NRA of exporting country received (in case of imported products)

□ Yes

□ Exemption Certificate

3.

Batch Production Record received (for locally manufactured products).

□ Yes

□ No

4.

Copy of the Registration Letter received.

□ Yes

 

5.

Copy of the endorsed paid bank challan received.

□ Yes

 

6.

Copy of endorsed Invoice received.

□ Yes

 

Date of Receipt

 

Received By (sig)

 

Application accepted

□ Yes

Name

 

If rejected (reason)

 

Designation

 

 

 

 

 

Assessment required

□ Summary protocol review

□ Laboratory Access

Assigned reviewer

 

 

Deadline for assessment

 

 

 

 

 

 

 

 

 

 

 

Director/FGA

 


Controlled Document-003-1

 

LOT RELEASE CERTIFICATE

(For Human Biological Drug-Imported in Finished Form)

Examined under authority vide DRAP Act, 2012 (Act XXI of 2012) dated Nov 13, 2012 and in accordance with the Standard Operational Procedure for the Lot Release of Biological Products.

 


Certificate Reference Number

 

Date of Receipt of release application

 

Date of Issue

 

 

Trade Name:

 

International non-proprietary Name/common name :

 

Registration number:

 

Type of container:

 

Dosage form

 

Batch number appearing on the package:

 

Total number of containers of this batch received in the country:

vide invoice no and

date:

 

Date of manufacture:

 

Date of expiry:

 

Name and address of the present Registration number holder and importer:

 

Storage temperature

 

 

It is certified that as a minimum this release certificate is based on the review of protocols for manufacturing and quality control test results therein. The lot mentioned above has been approved for release based on the information as provided by the importer in the Summary Protocol submitted according to approved market authorization dossier and the lot release certificate of country of origin.

 

This certificate relates to the quality of the mentioned lot when it is imported, packed, stored and distributed under proper cold chain, and when the records are available for verification of the same.

 

 

_________________________________

Director /Federal Government Analyst

 

           

Annex-4

 

Schedule of Lot Release Fees

 

Imported Vaccines, Sera and Interferon:

The lot release fee for all the imported vaccines, sera and interferon is Rs. 20,000.00 per lot/sample.

 

Locally Manufactured Vaccines, Sera and Interferon:

            The lot release fee for locally manufactured products is given below:

 

Product

Fee per sample (in rupees)

Tetanus Toxoid.

30,000.00

Anti Tetanus Sera.

30,000.00

Oral Polio Vaccine.

20,000.00

Measles Vaccine.

20,000.00

Rabies Vaccines.

30,000.00

Hepatitis-B Vaccine.

20,000.00

Snake Venom Anti Sera.

30,000.00

Interferon

20,000.00

 

Note:

            The lot release fee should be submitted at any branch of Allied Bank on the prescribed deposit slip available in the branches of Allied Bank in favor of head of account as given below:

                        Account No:               0010008463700018

                        Bank:                           Allied Bank

                        Branch:                        Civic Centre G-6, Islamabad.

                        Title of Account:         Drug Regulatory Authority of Pakistan.

 


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