February 2007

Frequently-Asked Questions (FAQs) about Quality-Control Testing of Pharmaceutical Products Used in the Prevention and Treatment of HIV/AIDS, Tuberculosis and Malaria to be Purchased with Global Fund Resources
Introduction and Generalities Quality Control Requirements for Multi-source Pharmaceutical Products Quality Control Requirements for Single- and Limited Pharmaceutical Products complying with A and B options Quality Control Requirements for Single- and Limited Pharmaceutical Product complying with C option

Introduction and Generalities

1 What is quality control? Quality control is one element of the overall Quality Assurance (QA) process and refers to the testing of samples of all pharmaceutical products against specific standards. The objective of testing medicines in a certified laboratory is to evaluate the continuous compliance of the products with the manufacturers requirements and specifications. 2 - Should each pharmaceutical product purchased with Global Fund resources be tested? Yes. Under the Global Funds procurement policy, multi-source as well as single- and limitedsource pharmaceutical products (whether under the definition of Option A, B or C) should be tested. 3 What do the terms multi-source and single- and limited-source pharmaceutical product refer to? The full definition of multi-source and single- and limited-source pharmaceutical product is available on the Global Fund website at: http://www.theglobalfund.org/en/about/procurement/quality For the Global Fund, the main difference between the two categories of product is the following: Multi-source pharmaceutical products are products for which there is a publicly-available monograph for the finished-dosage form in the International Pharmacopoeia, the British Pharmacopoeia or the United States Pharmacopoeia. For single- and limited-source pharmaceutical products, there is no monograph for the finished-dosage form publicly available.

4 - What do the terms Option A, Option B and Option C refer to? The Global Fund' policy regarding the eligibility of single- and limited-source medicines for s purchase with Global Fund resources specifies three acceptable QA standards. Option A includes all products pre-qualified by the WHO Prequalification Program. Option B refers to products authorized for use by a stringent regulatory authority Option C includes Ci and Cii options: Ci is for those products for which an application have been sent for approval to WHO Prequalification Program or to a stringent Regulatory Authority and which are manufactured

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at a site that is compliant with the standards of good manufacturing practices (GMP), as certified (after inspection) by WHO or a stringent regulatory authority.

Cii is for those products which are manufactured at a site that is compliant with the standards of good manufacturing practices (GMP), as certified (after inspection) by WHO or a stringent regulatory authority.

5 - Should each batch of pharmaceutical product purchased with Global Fund resources be tested? No. It is not necessary for every batch to be tested. Batches will be randomly selected for testing by the entity responsible for testing activity.

Quality Control Requirements for Multi-source Pharmaceutical Products

1 - Who is responsible for the testing of Multi-source pharmaceutical products? For these pharmaceutical products, it is the responsibility of the purchasing entity (PR or subrecipient) to ensure that the samples are tested according to the Global Funds QA policy. The costs of testing should be included in their budget. This responsibility is generally assumed by the person responsible for the overall QA of the grant. 2 - At what point should these pharmaceutical products be tested? For all these pharmaceutical products, the entity responsible for QA under a grant must systematically draw samples of each pharmaceutical batch. Then the samples should randomly be subjected to quality control testing. 3 - Who will perform the tests for these pharmaceutical products? The PR responsible for the grant must select the testing laboratory, which must be either the NDRA laboratory or a laboratory recognized by the NDRA of the recipient country. The laboratory should have sufficient capacity to conduct full pharmacopoeia testing. They must meet one of the following criteria: Acceptance for collaboration with WHO Prequalification Project ( refer to the pre-qualified laboratory list on WHO website); http://mednet3.who.int/prequal/default.htm Accreditation in accordance with ISO 17025; Acceptance by a stringent authority.

4 Can the laboratory selected by the GF Secretariat for Quality Control of C pharmaceutical products be also selected by the PR? Yes, a PR can select the laboratory contracted by the GF for quality control of C pharmaceutical products, to perform the tests. The entire process falls under the PRs responsibilities. (This laboratory is SGS laboratory) 5 - What is the testing process which will be followed for these pharmaceutical products? The PR should agree with the selected laboratory the relevant assays to be performed (normally those tests which would show deterioration of the product, if any).

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The main national and/or international requirements applicable to quality control of pharmaceutical products should be followed. 6 - What are the possible outcomes of the quality control testing process of pharmaceutical product? If the results of the tests are not acceptable (meaning outside the limits of the specifications) the PR and the supplier should be immediately informed. The PR must find an alternative product to procure and replace the products, if necessary.

Quality Control Requirements for Single- and Limited-Source Pharmaceutical Products Complying with Option A or Option B
1 - Who is responsible for the testing of samples under Option A or Option B? For these pharmaceutical products it is the responsibility of the purchasing entity (PR or subrecipient) to ensure that the samples are tested according to the Global Funds QA policy. The costs of testing should be included in their budget. This responsibility is generally assumed by the person responsible for the overall QA of the grant. 2 - At what point should these pharmaceutical products be tested? For all these pharmaceutical products, the entity responsible for QA under a grant must systematically draw samples of each pharmaceutical batch. Then the samples should randomly be subjected to quality control testing. 3 - Who will perform the tests for these pharmaceutical products? The PR responsible for the grant must select the testing laboratory, which must be either the NDRA laboratory or a laboratory recognized by the NDRA of the recipient country. The laboratory should have sufficient capacity to conduct full pharmacopoeia testing. They must meet one of the following criteria: Acceptance for collaboration with WHO Prequalification Project ( refer to the pre-qualified laboratory list on WHO website); http://mednet3.who.int/prequal/default.htm Accreditation in accordance with ISO 17025; Acceptance by a stringent regulatory authority.

4 Can the laboratory selected by the GF Secretariat for Quality Control of C pharmaceutical products be also selected by the PR? Yes, a PR can select laboratory contracted by TGF for quality control of C pharmaceutical products, to perform the tests. The entire process falls under the PRs responsibilities 5 - What is the testing process which will be followed for these pharmaceutical products? The PR should agree with the selected laboratory on the relevant assays to be performed (normally those tests which would show deterioration of the product, if any). The main national and/or international requirements applicable to quality control of pharmaceutical product should be followed.

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6 - What are the possible outcomes of the quality control testing process of pharmaceutical product? If the results of the tests are not acceptable (meaning outside the limits of the specifications) the PR and the supplier should be immediately informed. The PR must find an alternative product and replace the products, if necessary.

Quality Control Requirements for Single- and Limited-Source Pharmaceutical Products Complying with Option C (Ci and Cii)
1 Who is responsible for the testing of samples? For pharmaceutical products purchased under Option C, it is the responsibility of the Global Fund Secretariat to order and pay for the tests. 2 - At what point should pharmaceutical products be tested? Pharmaceutical products purchased under Option C should be tested as soon as the purchase of such product is planned and before any shipments of batches stored at the manufacturing site (or at procurement agent facilities) are expedited to the recipient. 3 What is the specific procedure mandatory for and applicable to Option C pharmaceutical products? The quality control testing procedure for products purchased under Option C is the following: If the Principal Recipient (PR) intends to buy pharmaceutical products under Option C, they must notify in written the Fund Portfolio Manager (FPM). The Global Fund Quality Assurance Officer (QA Officer) reviews the compliance of the selected pharmaceutical products with the Global Fund QA Policy. If the Global Fund QA Officer has no objections, they will inform both the laboratory and the PR. Laboratory contacts the supplier to request the relevant documentation. Laboratory selects batches for testing and performs the required tests. The QA Officer takes the final decision on the basis of the laboratory report . The QA Officer, together with the FPM, informs the PR and the supplier of the final test results and the Global Funds decision.

4 - Can the supplier send Option C pharmaceutical products which are being tested to the PR before receiving Global Funds decision? No, all the batches which are being tested should be kept by the supplier at the manufacturing site or by the procurement agent at procurement agent warehouse site, until the end of the testing and receipt of the Global Funds decision.

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5 - Who will perform the tests for the pharmaceutical products procured under Option C? One laboratory, SGS Netherland B.V, was selected through a competitive process, as recommended by the Board. The contract between SGS and the Global Fund was signed in October 2006. 6 What is the testing process which will be followed for Option C pharmaceutical products? The quality control testing will include the following steps: Step A - Sampling at manufacturing sites SGS will select random samples of different batches (two to five batches) at the manufacturing site. Step B - Implementation of manufacturers methods SGS will review the manufacturers methods for quality control, using for this review the Standard Operating Procedures developed by the manufacturer, the validation data obtained by the manufacturers and the Certificate of Analysis of each batch tested. Tests will also be performed to evaluate the feasibility of the methods and to implement them. Step C - Routine quality control tests of batches After implementation of the methods, SGS will then duplicate the manufacturers quality control testing on the batches selected at random at the manufacturing site. 7 - Which parameters will be tested? The following parameters will be tested and reported: Appearance; Identification, assay, and impurity control; Dissolution or disintegration (for tablets and capsules); Content uniformity or weight variation (for tablets and capsules); pH and microbial limits for the solutions (if in the specifications); Sterility and bacterial endotoxin test (for injectables).

8 - What will the SGS laboratory request from the supplier in order to undertake testing activity on pharmaceuticals purchased under Option C? For implementation of the manufacturers methods: Manufacturers standard operating procedures for quality control; Manufacturers validation report for test methods; Characterized standards and reference materials in sufficient quantity for method installation, debugging and final method transfer testing with certificates containing at least: content, purity, water content, expiry date; Manufacturers specification sheets for each product formulation with testing parameters and acceptance limits; Sufficient samples from two different batches of each product formulation to perform testing for method transfer; Certificates of analysis (CoA) of the product batches involved in method transfer; List of QC/QA contact persons for each manufacturer for technical discussions on analytical methods.

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For routine quality control tests (for each batch): Packaging order number, packing list (including product details) and batch numbers, sampling address, etc; Sufficient samples from two sets of tests for each product batch selected; Certificates of analysis of the product batches involved.

For the interpretation of the results, the specifications used will be those which were submitted to the NDRA of the purchasing country as part of the products registration process.

9 - What information will SGS laboratory provide to the Global Fund Quality Assurance Officer for decision-making? SGS will provide the Global Fund QA Officer with the report of the implementation of the methods, the Certificate of Analysis of batches tested, the full analytical report of the test performed by SGS as well as their conclusions, and the recommendations. 10 - What are the possible outcomes of the quality control testing process of Option C pharmaceutical products? The product can be supplied to the PR only if the results have been found to be within the manufacturers specifications. If the results of the tests are not acceptable (meaning outside the limits of the specifications) the PR and the supplier are immediately informed and the PR must find an alternative product to procure. 11 - Will the test results be publicly available? The test results will not be publicly available. Only the supplier and the PR and/or the procurement agency will receive the results. However, to avoid duplication of work, the Global Fund reserves the right to share the results with its partners upon request. 12 - How is the confidentiality of information provided by the supplier ensured? SGS has signed a confidentiality agreement as part of its contract with the Global Fund. Information received by the Global Fund will remain confidential.

For any additional questions, please contact your Fund Portfolio Manager or Joelle Daviaud, Procurement Team at: joelle.daviaud@theglobalfund.org and Tel : +41 22 791 17 58

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_________________________________________________________________________ The Global Funds Quality Control Requirements