1. Manufacturers' perceptions of WHO medicines prequalification Arab Union of the Manufacturers of Pharmaceuticals and Medical Appliances Amman, Jordan, 13 June 2013 Jacqueline Sawyer

2. Surveys, interviews and the business case Survey: finished pharmaceutical product manufacturers in 2010 Investigation of "business case": prequalification manufacturers of medicines for HIV/AID, TB and malaria in 2011 Quality research: active pharmaceutical ingredient manufacturers in 2012 Investigation of "business case": prequalification for manufacturers of reproductive health medicines in 2012 Considering research into antiretroviral supply/market page n °2 Manufacturers' perceptions of WHO medicines PQ | Amman | June 2013

3. Why seek to understand our customers? Stakeholders requested that WHO conduct a review of the PQP process: e.g. Gates Foundation: "Instilling a service orientation …satisfying…customers is important to maintain a well functioning programme…" Successful companies understand why their customers appreciate them and what they must do to keep them satisfied Successful companies optimize use of their resources to provide greater customer satisfaction In 2010 PQP sensed that it was doing some things well but couldn't articulate these clearly or fully Neither could it clearly describe its weak "service" points Manufacturers' perceptions of WHO medicines PQ | Amman | June 2013 page n °3

4. Perceptions of FPP manufacturers (1): service quality measurement PQP assessment and inspection activities reflect those carried out by national regulatory authorities Therefore the survey was designed to:  measure the level of service provided by PQP  how these compared to the level of service expected/desired from regulatory authorities Covered:  process dimensions such as: consistency of policies and procedures; feedback mechanisms; problem-solving options, complaint handling  delivery (people) dimensions including: reliability; responsiveness; empathy; "tangibles” (e.g. visually appealing reports, etc.) page n °4 Manufacturers' perceptions of WHO medicines PQ | Amman | June 2013

5. Perceptions of FPP manufacturers (2): survey development process Obtained input from within PQP and from regulatory and quality assurance pharmaceutical professionals Internal working sessions and in-depth phone interviews with industry professionals familiar with PQP Emphasis on identifying, from a participant's point of view, important stages in the WHO medicines prequalification process: aspects that were work well and those that fell short of expectations Individuals invited to complete the questionnaire had participated in WHO prequalification during 2006 ‒ 2010 Questionnaire completed on-line (invitation only) page n °5 Manufacturers' perceptions of WHO medicines PQ | Amman | June 2013

6. page n °6 Manufacturers' perceptions of WHO medicines PQ | Amman | June 2013 Perceptions of FPP manufacturers (3): survey development process

7. Base: Manufacturers (Quality Assurance), n=23 Red = minimum Green = desired Blue (square) = PQP performance 6.3 6.1 6.3 6.2 5.5 5.7 5.6 5.8 6.0 4.2 5.0 4.7 5.1 4.3 1.0 2.0 3.0 4.0 5.0 6.0 7.0 Providing clear interpretation of GMP requirements Providing an efficient process to resolve issues and questions raised following the inspection A process that makes efficient use of manufacturers’ time The clarity of questions asked during the inspection process Including inspectors from your country or region on the inspection team Average Rating page Manufacturers’ perceptions of WHO medicines PQ | Amman | June 2013 n °7 Perceptions of FPP manufacturers (4): service design: inspections

8. Perceptions of FPP manufacturers (5): Survey findings PQP = well designed, well executed programme Manufacturers generally satisfied with PQP and find value in participating Manufacturers place a premium on feedback, communications and problem resolution during prequalification process – especially for assessment of product dossiers – and these were potential improvement areas in the service design of the PQP After survey PQP improved: guidance on in-person meetings with PQP team; guidance on action to take in event of disagreement with assessment or inspection findings; review of stringency of WHO GMP requirement s page n °8 Manufacturers' perceptions of WHO medicines PQ | Amman | June 2013

9. Perceptions of the business case: manufacturers of HIV/AIDS, TB and malaria medicines (1) page n °9 Manufacturers' perceptions of WHO medicines PQ | Amman | June 2013

10. Manufacturers' perceptions of the business case: manufacturers of HIV/AIDS, TB and malaria medicines (2) page n °10 Manufacturers' perceptions of WHO medicines PQ | Amman | June 2013 StrategyR&D/Regulatory Director Corporate StrategyAssociate VP Regulatory Affairs Sr Executive Strategic Trade DevelopmentDevelopment Director SVP Sales and Portfolio ManagementVP Technology

11. Manufacturers' perceptions of the business case: manufacturers of HIV/AIDS, TB and malaria medicines (3) "Business attractiveness" differs for different types of company depending on their "drivers" (motivations) page n °11 Manufacturers' perceptions of WHO medicines PQ | Amman | June 2013

12. Manufacturers' perceptions of the business case: manufacturers of HIV/AIDS, TB and malaria medicines(4) For example, "knowledge seekers": Want to be capable of participating in the global medicines market Aware would not pass stringent regulatory application with current manufacturing and/or skill sets Need training from experts, see PQP as a learning opportunity Value proposition PQP  produce quality-assured products for local or global markets For example, "international generics": Established access to international and local markets Manufacturing export-focused, sometimes part of larger multi-nationals Want to fill “low-cost” manufacturing capacity, focus on volume & margins Some degree of social responsibility Value proposition PQed products  incremental volume for PQed & other portfolio products page n °12 Manufacturers' perceptions of WHO medicines PQ | Amman | June 2013

13. Business attractiveness: direct and indirect benefits page n °13 Manufacturers' perceptions of WHO medicines PQ | Amman | June 2013

14. Manufacturers' perceptions of API prequalification (1) 2010 PQP established programme to prequalify active pharmaceutical ingredients (APIs) Unique programme because even stringent regulatory authorities do not publish a list of API-sources that are of assured quality and verified GMP With API PQ entering its third year, WHO wanted to assess the programme from the standpoint of participating manufacturers page n °14 Manufacturers' perceptions of WHO medicines PQ | Amman | June 2013

15. Manufacturers' perceptions of API prequalification (2) Areas of investigation Manufacturers’ rationale for participation in the PQ API How manufacturers would evaluate PQP's performance Sources of technical assistance manufacturers use to assist to prepare APIMF or reach GMP at manufacturing sites Impacts of prequalified APIs on manufacturers’ businesses (e.g. changes in market share, price levels, etc.) Benefits and drawbacks of the current programme. Manufacturer views on the API PQ programme going forward: In what ways will the programme be of (increasing) benefit over time? How will the programme affect market dynamics? page n °15 Manufacturers' experience with WHO medicines PQ | Amman | June 2013

16. Manufacturers' perceptions of API prequalification (3) Participants' objectives Manufacturers reported a wide range objectives for their involvement in the API-PQ, including: sell API to other manufacturers improve the company's management of APIs internal capacity building, improve the R&D function improve quality reputation of products and increase credibility Develop markets for products, improve market potential of firm, participation in tender offers, increase market share, entry into new markets Serving public health by achieving faster product approval via prequalification page n °16 Manufacturers' perceptions of WHO medicines PQ | Amman | June 2013

17. Manufacturers' perceptions of API prequalification (4) Disadvantages Audits are conducted on a product-by-product basis which can lead to multiple inspections at the same site Process takes a lot (or too much) time Potential for company to make money on products or obtain a good ROI is unclear WHO response times can be inconsistent WHO more strict than FDA or EMA (e.g. employee protection and environment protection) High costs to participate (e.g. re-modifying costs, production stoppages, etc.) After PQ, must still obtain registration in each country entered page n °17 Manufacturers' perceptions of WHO medicines PQ | Amman | June 2013

18. Manufacturers' perceptions of API prequalification (5) Benefits to participants Many benefits are aligned with previously-mentioned company objectives: develop new markets for products; increase sales volume; increase market share improved company management, R&D capabilities, product quality, quality management system, documentation (regulatory and GMP), business results a opportunity to sell prequalified APIs to other (FPP) manufacturers ability to charge higher prices for products "intangible" benefits: serving the needy; getting global recognition as one of the few firms participating in the programme page n °18 Manufacturers' perceptions of WHO medicines PQ | Amman | June 2013

19. Manufacturers' perceptions of API prequalification (6) Challenges Regarding APIMFs, e.g.: …research on and control of impurities…chemical characterization…dealing with WHO standard on solvent recovery…must check every batch for genotoxicity control…no clear guidelines on handling variations in the master file …assessors can differ significantly in how they review documents (i.e. different review styles) Regarding GMP, e.g.: …clean room requirements…movement of personnel, water and materials…process validation of core solvents and core materials…no guideline for API GMP other than TRS-937, which is actually intended for FPP manufacturers… qualification of equipment systems and utilities…differences between previous manufacturing standards and WHO GMP standards page n °19 Manufacturers' perceptions of WHO medicines PQ | Amman | June 2013

20. Manufacturers' perceptions of API prequalification (7) Corrective action Have not yet published APIMF specific amendment guidance, but have published one for FPP manufacturers and the technical content relating to APIs in this document is useful guidance pending issue of API-specific guidance. To ensure greater consistency between assessors, have increased level of internal guidance for assessors and introduced template questions for assessors when requesting further information (which often created perception of differences). Posted procedure on PQP web site for API manufacturers who have already received stringent authority approval and wish to use this for the purposes of an abridged assessment. page n °20 Manufacturers' perceptions of WHO medicines PQ | Amman | June 2013

21. page n °21 Manufacturers' perceptions of WHO medicines PQ | Amman | June 2013

22. Manufacturers' perceptions of API prequalification (8) Future of the API Programme If the API-PQ makes changes and evolves as a regulatory pathway: “New markets will open up because of programmes like API- PQ” API-PQ promotes “fair competition on price and quality” Programme participants can expect more business in both existing and new markets; participants will see improved market recognition and standing; new players will be able to compete at international level Programme itself can expect to see more molecules submitted for approval page n °22 Manufacturers' perceptions of WHO medicines PQ | Amman | June 2013

23. Perceptions of the business case: Manufacturers of reproductive health medicines (1) Evaluate the differences in the business case between [HIV, TB, malaria, studied previously] and reproductive health (RH) medicines Assess the impact of being prequalified on … Revenue potential for pharmaceutical companies manufacturing reproductive health medicines. Improved market access (institutional/donor and non-institutional markets) Understand the impact of implementing a “PQP strategy” on manufacturers. Create a market segmentation scenario for RH manufacturers. page n °23 Manufacturers' perceptions of WHO medicines PQ | Amman | June 2013

24. Perceptions of the business case: Manufacturers of reproductive health medicines (2) RH market seen as less competitive than e.g. ARV or anti-TB markets Consumer focused – brand awareness  Often tenders request a branded product, especially at Ministry of Health level  NGOs can be loyal customers, often create their own brands  Some manufacturers create new brands for the institutional / donor market Many manufacturers focused on RH alone Planning by government or agencies usually poor; “family planning mindset” needed Ramifications of poor quality are not directly life or death and governments and local procurers often do not fully appreciate the benefits of quality page n °24 Manufacturers' perceptions of WHO medicines PQ | Amman | June 2013

25. Perceptions of the business case: Manufacturers of reproductive health medicines (3) Donor markets are more injectable and implant focused than US/Europe, which are focused on oral contraceptives Local private markets (which are larger than institutional markets) are also more oral contraceptive focused RH medicines have higher margins than first line ARVs, TB and malaria page n °25 Manufacturers' perceptions of WHO medicines PQ | Amman | June 2013

26. Antiretrovirals Changes in treatment guidelines Analysis of current situation for ARVs Capacity to meet new treatment needs Case study for tenofovir Do (historical or current) medicines shortages in other therapeutic areas have any lessons here? Concerned to ensure good balance between price and quality page n °26 Manufacturers' perceptions of WHO medicines PQ | Amman | June 2013