World Bank Training Program on HIV/AIDS Drugs

Transcription

1 World Bank Training Program on HIV/AIDS Drugs Training Module 4 Quality Assurance PART 2 based on the World Bank document Battling HIV/AIDS: A Decision Maker s Guide to the Procurement of Medicines and Related Supplies World Bank, 2004 adapted from presentation by Zubin Austin, PhD June 2005

2 Learning Objectives Upon completion of this module, you will be able to Explain the need for a systematic quality assurance process for pharmaceutical products Describe key elements of the quality assurance process for pharmaceuticals Discuss the procedures and standards for prequalification of suppliers of pharmaceuticals Apply quality assurance and supplier selection principles to case discussions

3 Rationale for this Module QUOTE ( WHO ): It is not the colour of the cat that it is important as long as it is able to catch the mouse.

4 Unit 3 Quality considerations in Pharmaceutical Procurement THE PROCUREMENT AGENT

5 Selecting and Sourcing Multi- Source Products Innovator vs. generic issues Specific issues related to interchangeability of products - stability, bioavailability, bioequivalence, etc. How are you, as a procurement agent, going to ensure QUALITY?

6 Product Selection Issues Unique nature of medicines heightens need for effective quality assurance All medicines used must be safe, effective, and of consistent quality Failure to select proper products will lead to treatment failure, drug resistance, wasted resources and human suffering 6

7 Identifying Product Suppliers requires a systematic approach Pre-qualification of suppliers and products Specifying supplier conditions in contract Monitoring quality of product and processes Continuous evaluation of supplier performance and product performance in clinical practice 7

8 Procedures for Prequalification of Suppliers Rationale More meaningful, effective, efficient and less expensive to eliminate sub-standard manufacturers and products at the opening of bidding/tendering than during the process Purpose Simplifying the process during adjudication makes it easier to ensure that products are manufactured in compliance with GMP and products meet established quality standards 8

9 Procedures for Prequalification of Manufacturers Local Procurement Committee comprising managerial, technical, and professional staff Manufacturers submit dossiers for review; must be reviewed/re-inspected at least every 3-5 years to ensure adherence to policies Review/re-inspection also performed if product changes occur that may impact on safety, efficacy, quality, manufacturing method, or location of manufacturing 9

10 Procedures for Prequalification of Manufacturers (Cont.) Verification of compliance with GMP Evaluation of Product Dossier Verification of compliance with good distribution practices Role of national drug regulatory organizations (in compliance with WHO standards) Random testing of samples 10

11 Prequalification: Evaluation of Product Dossier Specifications (in WHO guidelines) Must include details regarding: - Regulatory status - Pharmaceutically active ingredient(s) - Manufacturing processes / site - Finished product specifications (stability, bioavailability, interchangeability etc.) - Packaging/labeling/storage details - Product/patient information 11

12 Procedures for Prequalification of Manufacturers (Cont.) Other considerations: Financial viability of the supplier Production capacity Supply history supplier performance over period of time Lead times? 12

13 Prequalification: Evaluation of Product Dossiers Multi-source Products For products manufactured and registered in countries with a stringent regulatory authority, the product dossier presented may be the same as that presented to the regulatory authority Appropriate documentation/certification has to be provided if product differs in any way from product registered in original country (e.g. packaging, formulation, strength, manufacturing site, etc.) 13

14 Prequalification: Evaluation of Product Dossiers Single/Limited Source Products Include specifications of in-house quality-control and quality management practices in sufficient detail to allow replication by another laboratory Validation of in-house methods must be provided by manufacturer Quality assessment of products to be undertaken by external laboratory 14

15 Prequalification: On-going control / Testing of Samples Undertaken to verify compliance with standards and references provided in dossier Certificates of analysis, pre-shipment inspections Test samples should be from supplies, not from pre-supply batches On-going random sampling and quality control analysis post-supply Sampling framework when, what to test for? 15

16 Prequalification Verifications Compliance with GMP Inspections and certification of facilities Reliance on national regulatory authorities Data verification during follow up inspections Compliance with good distribution practices Quality assurance methods for selection of raw material suppliers, storage of products, transportation delivery of final product, etc. 16

17 Identifying Product Suppliers requires a systematic approach Pre-qualification of suppliers and products Specifying supplier conditions in contract Monitoring quality of product and processes Continuous evaluation of supplier performance and product performance in clinical practice 17

18 Contractual conditions Enforcing technical specifications in contracts Link technical specifications into contracts, to ensure enforcement of contractual agreements Include right to perform inspections and recertification of facilities, notification of changes minor changes, major changes Keep it simple (efficient), but effective 18

19 BUZZ Group Exercise 3 ( max 15 minutes ) QUESTION: Existing strategies for prequalifying suppliers and applying quality principles in contracts? Discuss in your group how countries in the MENA region are performing prequalification Identify the three things that are working well Identify three limitations / actions that do not really add benefit to the process 19

20 Unit 4 Quality considerations in Pharmaceutical Procurement THE WHO Pre-Qualification process 20

21 Pilot Procurement Quality and Sourcing Project To assess acceptability in principle of HIV/AIDS Drugs and Diagnostics for purchase by UN Agencies In an attempt to address the problem identified, WHO started a Pilot Project : Objective: Creating unified standards for performing inspections at manufacturing sites to assess compliance with WHO Good Manufacturing Practices. Evaluating information on product quality specifications of products submitted by suppliers. Taking the best from existing quality systems, filling the gaps and creating a single, harmonized quality system and assessment system for use by WHO and other UN Agencies. 21

22 Simplified process: WHO Perspective Issue Guidelines Receive Submissions Evaluate Submissions Communicate Decision Perform Inspections 22

23 Simplified Process: Manufacturer s Perspective Submit EOI Submit Site Master File Submit Product Dossier Submit Additional Data if needed Submit Corrective Action Plan if needed 23

24 Summary of Prequalification Processes 1. Dossier evaluation. Dossiers thoroughly evaluated for compliance with WHO recommendations and guidelines ("Marketing Authorization of Pharmaceutical Products with special Reference to Multisource (Generic) Products: a Manual for a Drug Regulatory Authority, WHO/DMP/RGS/98.5) and bio-equivalence data (Annex 9, WHO Technical Report Series No 863) 24

25 Summary of Prequalification Processes 1. Dossier evaluation (cont). ICH guidelines where appropriate to complement the aforesaid WHO recommendations and guidelines Where only in-house specifications exist, best expert judgement available today 25

26 Summary of Prequalification Processes Each dossier evaluated by a team of evaluators from both developed and developing countries Suppliers are informed of the outcome of the evaluation and are given the opportunity to submit additional data and information requested. Technical assistance provided to become PQ 26

27 Result A list of products, suppliers are provided on the internet and are regularly updated Data include manufacturing site and packaging materials, but not the source of the raw materials Procurement agencies that do not have the capacity to evaluate products can benefit from the list NO DELAY IN STARTING PROGRAMMES UNICEF/WHO partnership collect samples, forward to WHO for evaluation, linked to follow up inspections with data-verification 27

28 BUZZ Group Exercise 4 QUESTION: Experiences with WHO prequalification challenges in 2004 solutions generated in MENA region Open discussion 28

29 Conclusions GMP are aimed at reducing risks inherent in pharmaceutical production Qualification and validation provides confidence in manufacturers processes Prequalification provides greatest assurance regarding quality of pharmaceutical products, based on GMP inspections and product dossier evaluation Prequalification without effective contractual engagement has no benefit 29