WHO Prequalification

1. WHO Prequalification A catalyst for Quality Local Production – factors for success • 4 – 5 June 2019 • Deus Mubangizi • PQT Coordinator • mubangizid@who.int • Africa Pharma Conference 2019 • Johannesburg, South Africa

2. Outline of the presentation Purpose and status of national regulation and impact on access WHO PQ – responding to the need for access to quality assured health products PQ scope, procedures, workflow and pipeline PQ timelines, challenges and response measures Noted challenges to manufacturers and proposed solutions Benefits of PQ WHO-PQT: Looking to the future Take home messages

3. Purpose of regulation: Promoting and protecting public health Protecting Health: Market Control Promoting Health: Access

4. WHO GBT Performance Maturity Levels 3 2 1 4 ISO 9004 Continual improvement emphasized Stable formal system approach Reactive approach No formal approach WHO GBT Some elements of regulatory system exist Evolving national regulatory system that partially performs essential regulatory functions Stable, well-functioning and integrated regulatory system Regulatory system operating at advanced level of performance and continuous improvement Can ensure the quality of products if rely on ML 3/ ML 4 regulatory systems Target of WHA Resolution 67.20 Advanced and well resourced regulatory systems 50 Countries 100 Countries 44 Countries 74% 26% 4

5. Status of National Regulatory Systems by Maturity Levels (ML) 194 WHO Member States Facts • 51% have limited capacity to perform core regulatory functions • Applicants face a landscape of disparate regulations, frequent delays and limited transparency Implications • Access to quality assured and safe medicines and vaccines in countries at ML 1 & 2 • high risk of SF medical products • Cost of inefficient regulatory systems drives up prices • Regulators less prepared for public health emergencies

6. Background WHO responded to the need of procurement agencies and WHO Member States for quality-assured health products, by creating and applying quality-assurance mechanisms Vaccines Diagnostics Medicines Vector Control • Origin: Request by UNICEF and PAHOto evaluate quality, safety and efficacy of vaccines in the context of national immunization programmes • PQ beginning: 1987 • Origin: Request by WHO MS to assess the quality, safety and efficacy of low-cost and new FDCs HIV/AIDS generic medicines in response to MDGs • PQ beginning: 2001 • Origin: • Substandard performance of HIV assays in sub-Saharan Africa • Response: • HIV Test Kit Evaluation Programme (1988) • For initiation & monitoring Tx • PQ beginning: • 2010 • Origin: WHOPES set up in 1960 for evaluation of pesticides for public health. In 2015, WHO initiated reforms to foster innovation, improve efficiency, assure quality and align with other PQ programmes • PQ beginning: 2017

7. Prequalification workflow For each type of product, prequalification includes a comprehensive dossier assessment and a manufacturing site inspection, as well as other product-specific elements of evaluation Dossier submission Expression of interest (EOI) NRA functionality Programmatic suitability Screening Follow-up inspection Follow-up NOC Assessment Inspection capa Lab evaluation capa Inspection closing letter Letter of prequalification Web listing Public reports (WHOPAR, WHOPIR) Prequalification decision Maintenance and monitoring Collaborative registration Variations Annual reports Requalification Routine inspections Special inspections Handling complaints

8. https://extranet.who.int/prequal/key-resources/documents/summary-fpps-and-apis-invited-prequalificationhttps://extranet.who.int/prequal/key-resources/documents/summary-fpps-and-apis-invited-prequalification

9. Median times to PQ for FPPs- Full assessment route 270 days

10. PQ’s response to long manufacturer’s time • Measures to try to reduce manufacturer time to prequalification • Pre-submission meetings – Now mandatory for all new applicants – since late 2017. Gaps in QOS-PD discussed. • Strict response timelines for manufacturers introduced – 30, 60 or 90 days depending on the deficiencies – since late 2017 • Common Deficiencies in Finished Pharmaceutical Product (FPP) Dossiers – additional guidance to manufacturers - Feb 2018 • Annual PQ Quality workshop for manufacturers - 1st in July 2018 an 2nd in July 2019 in Copenhagen, Denmark • Model product dossier published to guide new applicants - 2016 • Specific guidance on Bioequivalence Studies– list of guidance continuously updated • PQ review of manufacturer BE protocols before studies – always strongly recommended

11. Fast track to prequalification • = prompt, complete, good-quality responses to PQ’s questions, throughout the process. Good quality dossier at submission +

12. Challenges and suggested solutions • Build R&D Capacity • Partner with academia and research institutions • Technology transfer • Sourcing of raw materials • Use prequalified APIs/CEPs • Strategic partnerships • Joint vendor audits • Pooling orders • BE studies • Pre-approved protocols • Use PQ listed comparators • Build CRO capacity • QMS/maintenance culture • Preventive maintenance • Develop a quality culture Limited R&D Inadequate pharmaceutical development Inadequate products and process knowledge Challenge addressing deviations and changes Challenge in sourcing and evaluation of raw materials Sourcing from brokers and distributors Batch to batch variations Inherent quality gaps built in the product Inadequate BE studies Poor design of BE studies Poor choice of comparator Poor GCP compliance Inadequate QMS/maintenance culture Deteriorating premises and equipment QMS not kept up-to-date

13. Benefits for stakeholders WHO prequalification serves as a guarantee of good quality for health products, is a reference in terms of internal technical expertise and has the power to convene external expertise Patients • Access to quality-assured products, adapted to their specific needs • Accurate prevention, diagnosis, and treatment WHO Member States & NRAs • Reduced burden for regulatory approval • Increased regulatory capacity & harmonization of regulatory practices in WHO MS • Implementation of specifically developed and road-tested international guidelines • Access to quality-assured products Donors, procurers and UN agencies • List of prequalified products • Increased availability of quality-assured products • Monitoring quality of prequalified products • Healthy market: diversity and affordability of products

14. Benefits for stakeholders WHO prequalification serves as a guarantee of good quality for health products, is a reference in terms of internal technical expertise and has the power to convene external expertise Manufacturers • Access to donor-sponsored tenders and MPP licences • Faster regulatory approval – using CRP • Timely assessment of variations and changes • PQ of APIs - Sources of quality APIs • International quality-assured product status (improved image) • Recognition of GMP status, beyond prequalified products • Increased capacity in quality management systems • Target Product Profiles • Harmonization of regulatory practices within WHO Member States • Reduced operating and manufacturing costs QC labs • International recognition of prequalified QCLs • Technical assistance and scientific advice

15. WHO-PQT: Looking to the future • Continue to assess and facilitate access to quality assured health products. • Gradually expand scope of PQ to cover more products on the EML through: • setting up criteria for prioritisation and gradual scope expansion • NCDs (Cancer/SBP pilot, Diabetes/Insulin, Hypertension, etc.) • IVDs for Cholera, TB, NCDs, NTDs/Dengue • Gradually expand the mechanisms for PQ through: • Expand the abridged assessment of products approved by WHO Listed Authorities assessed using the GBT. • Reliance on quality assured regional-network-joint-assessments. • Expand mechanisms to evaluate new products developed with special focus on LMICs and emergencies (EU Art.58, Swiss EUL) • Expand risk based approaches like ERP, ERPD and other mechanisms - Snake anti-venoms and other products on the EML.

16. Take home messages • WHO Prequalification: • Contributes to access and achieving SDGs and UHC • facilitates access to quality assured priority health products • Role recognized by WHO 13th General Programme of Work: 2019 - 2023: • The Organization will continue to support the availability of quality-assured generic products for procurement by global agencies and countries through the WHO prequalification programme, which will evolve to meet the changing health needs of countries. • Has been instrumental in building national capacity for the manufacture, regulation and monitoring of medicines – promoting harmonization and convergence • Stepped up global leadership: • PQ has been recognized as a stamp of quality and a point of reference for QA for UN, International, regional and national procurement

17. Diagnostics • Irena Prat • diagnostics@who.int • Medicines • Matthias Stahl • prequal@who.int • Vaccines • CarmenRodriguez Hernandez • vaccprequalification@who.int • Inspections • Johanna Gouws • prequalinspection@who.int • Technical assistance & laboratories • Rutendo Kuwana • prequallaboratories@who.int • Prequalification team • Deus Mubangizi • PQT Coordinator • mubangizid@who.int • https://www.who.int/medicines/regulation/prequalification/en/ • Vector control • Marion Law • pqvectorcontrol@who.int Collaborative registration procedure Luther Gwaza prequalreg@who.int Dankie