11/11/2013
Lot Release
SOP (STANDARD OPERATING PROCEDURE)
SOP No. 036/A-NCL-LR
Title: Procedure for Lot Release of Biological Products.
Effective Date: May, 27, 2013
Version: 06
Next Review date: December, 2013
Document History:
Version
Effective date
Significant Changes
Previous Version
00
01.09.2006
Initial version
-
01
01.02.2007
Revision after discussion with stake holders
00
02
01.10.2010
Revision for: correction in job assignment of FA;
01
03
11.04.2011
Revision for: Correction of SOP number, correction of job assignment of FA; use of the term Biological Drug in place of words vaccine, sera, and biological product(s); provision of relevant rules (SRO) applicable to the activities; rearrangement of paragraphs for logical understanding of events; clarification when to submit LR request for locally manufactured biological drugs. Definition of Lot Release given.
02
04
31.05.2012
Clarification in sections 1.3, 2.2 and addition of section 2.4 regarding the non-application of lot release system to veterinary drugs.
03
05 01.02.2013 Change Section 1.3, lot release is now under DRAP Act, 2012 04
06 27.05..2013 Changes in following sections to make this SOP in line with DRAP Act, 2012 and recent court proceedings in differed cases to ensure safety of biological drugs.
Minor changes, additions and deletion in Sections 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.
New Section 1.4
Addition of section 5.2.3,
Clarification of field samples and lot release samples: Section 6.1.3
Changes in Annex I 05
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 a Biological Drugs into the market.
1.2. Lot Release of Biological Drugs is performed within the framework of Schedule I, of DRAP Act, 2012.
1.3. The Schedule I of DRAP Act, 2012 shall apply for the definition of “Lot Release” and of “Biological Drugs”, (please see section 2.4).
1.4 Lot release and field samples testing clarification is given in section 6.1.3
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 to the Drugs (Specifications) Rules, 1978.
2.2. This applies to all 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 782(I)/2000 dated 2nd November 2000, (please see section 2.4 for veterinary biological drugs) and as per Schedule I of 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 Biologicals Drugs meant for human use and is based on W.H.O. recommendations, 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 the procedure described in this SOP while submitting the request for Lot Release of an already registered Biological Drug.
3.2. Authorized officer (Officer notified by the Federal Government for the release of Biological Drug) 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 (Annex-3).
4. REQUIREMENTS:
4.1. Summary Protocols of each lot. (Summary Protocol is defined as: “A document summarizing all manufacturing steps and tests performed along with results for that particular lot of Biological Drug, 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 Drug in the country of origin.
4.3. Batch Production Record (BPR) of the particular lot (for locally manufactured Biological Drugs only).
4.4. Lot Release fee for each lot. The Lot Release fee may be revised from time to time by the Policy Board of DRAP.
4.5. Copy of the paid Bank Receipt.
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 to the Authorized Officer (Officer notified by the Federal Government for the release of imported Biological Drugs at the port of entry) who grants provisional release of the consignment. This is to take the consignment from port of entry to the importer’s warehouse cold room for proper storage, within a time period not exceeding two working days, with the directions 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 on the prescribed form (Annex-2) and sends the specified quantity of sample of each lot/batch, within a week, directly to National Control Laboratory for Biologicals to obtain Lot Release Certificate, 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 shall apply the prescribed procedure applicable to each Biological Drug and shall issue a Lot Release Certificate with information as prescribed (Annex-3). The time frame applicable for each lot review ranges 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 Drugs 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 Drugs at the port of entry) shall grant permission to the importer, within two working days of receipt of Lot Release Certificate, to place the particular Biological Drug on the market for use.
5.2. Locally manufactured biological products:
5.2.1. Upon completion of manufacturing process, quality control testing and quality assurance review of each lot, within a week the manufacturer submits the Batch Processing Record along with the sample of each lot/batch in quantity specified by National Control Laboratory for Biologicals, directly to National Control Laboratory for Biologicals to obtain Lot Release Certificate. The request is submitted on prescribed form (Annex-2) 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 shall initiate the internal process of lot review (as per SOP 36-NCL-LR) and shall issue a lot release certificate 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 their BPRs which type of Biological Drugs they are manufacturing. Manufacturers are encouraged to get their old registration letters updated by July 30, 2013 to clearly specify what is being manufactured locally from the imported material.
6. SAMPLING:
6.1.1. Representative samples of each lot are collected by importer and/or manufacturer, in quantity specified by National Control Laboratory for Biologicals.
6.1.2. Sample 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.
6.1.3. 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 used in court proceedings for field samples. Filed samples are to picked up by the relevant FID or PDI as per approved and notified procedure under DRAP Act, 2012 and Drugs Act, 1976 and the 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.
6.1.3. 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, Islamabad.
6.1.4. The samples should be sent in accordance with the temperature requirements of the Biological Drug.
7. APPEALS AGAINST DECISION OF NATIONAL CONTROL LABORATORY FOR BIOLOGICALS:
7.1. In case of the final rejection of the request for Lot Release of a 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.
8. REFERENCE DOCUMENTS:
8.1. Annex-1: Quantity of samples.
8.2. Annex-2: Lot Release request form.
8.3. Annex-3: Model Lot Release Certificate.
8.4. Annex-4: Schedule of testing Fees.
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Annex-1
Quantity of samples of Biological Drug 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. Therefore, the request for the release of such Biological Drugs 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..
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Annex-2
LOT RELEASE REQUEST FORM
The Director/Federal Govt. Analyst, No.
National Control Laboratory for Biologicals, Dated:
Cabinet Division
Islamabad.
Please find enclosed herewith sample of Biological Drug as detailed below along with the required documents, for the grant of Lot Release Certificate.
Product name _______________________________________________________________
Manufacturer ________________________________________________________________
Date of receipt of shipment (in case of imported products) ____________________________
Lot No. ____________________________ Lot size/quantity. _____________________
Mfg. date __________________________ Expiry date __________________________
Pharmaceutical form _________________ Doses/Vial __________________________
Diluent ____________________________ Diluent lot No. _______________________
Storage conditions ___________________ Quantity of sample ____________________
Sample conditions ____________________________________________________________
Requested By:
Name _____________________________ Title _______________________________
Signature __________________________ Date _______________________________
Address ____________________________________________________________________
____________________________________________________________________
For official use only:
Date of receipt _____________________ Quantity of samples __________________________
Sample conditions _______________________________________________________________
Summary protocol received □ Yes □ No
Lot release certificate from NRA of exporting country received (in case of imported products).
□ Yes □ No
Internal release certificate of the manufacturer received (for locally manufactured products).
□ Yes □ No
Copy of the paid bank challan received. □ Yes □ No
Copy of Invoice received. □ Yes □ No
Received by: __________________________
Assessment required: Summary protocol review / Laboratory access
Assigned reviewer: ______________________________________________________________
Deadline for assessment: _________________________________________________________
_____________________
Director / FGA
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Annex-3
LOT RELEASE CERTIFICATE
MINIMUM INFORMATION TO BE INCLUDED ON THIS CERTIFICATE,
ACTUAL MAY VARY FROM PRODUCT TO PRODUCT AND THE MANNER IT IS MANUFACTURED.
Ref. No. Dated:
The following Lot of ___________________________________________________ produced by __________________________________ in ______________________ whose lot number appears on the label of the final container, received from ___________________________________ bearing No. _______________________ dated _______________meets / does not meet:
i. All national requirements.
ii. W.H.O. Requirements for Biologicals _________________________________ Requirements for _________________________________________.
iii. W.H.O. General Requirements for Manufacturing Establishments and Control Laboratories.
Lot No.
Manufacturing Date
Expiry Date
Quantity
It is certified that as a minimum this release certificate is based on the scrutiny of the manufacturing and testing protocols.
THE ABOVE LOT OF THIS BIOLOGICAL PRODUCT IS APPROVED/ REJECTED FOR RELEASE.
_____________________________________
Director / Federal Government Analyst
*As a minimum this certificate is based on scrutiny of the manufacturing and testing protocols.
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Annex-4
9. Schedule of Lot Release Fees
Imported Biological Drugs:
FEES ARE TO BE DETERMINED BY THE POLICY BOARD OF THE DRAP AND ARE TO BE DEPOSITED AT THE DESIGNATED BRANCHES OF ALLIED BANK OF PAKISTAN ON SPECIALLY PRINTED DEPOSIT SLIPS.
REGULATORY MANAGERS OF THE COMPANIES ARE TO CONSULT THE ACCOUNTS OFFICER OF DRAP FOR LATEST DEVELOPMENTS IN THIS REGARD.
