WHO Prequalification of in-vitro diagnostics, medicines and vaccines

Transcription

1 WHO Prequalification of in-vitro diagnostics, medicines and vaccines Overview of prequalification processes & supporting activities Deus Mubangizi PQT Coordinator 20 October 2016

2 2 WHO prequalification of in-vitro diagnostics, medicines and vaccines Outline Introduction Prequalification role Prequalification process Supporting activities and procedures Conclusion

3 3 WHO prequalification of in-vitro diagnostics, medicines and vaccines Outline Introduction Prequalification role Prequalification process Supporting activities and procedures Conclusion

4 4 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 Diagnostics Origin: Substandard performance of HIV assays in sub-saharan Africa Response: HIV Test Kit Evaluation Programme (1988) PQ beginning: 2010 Medicines Origin: Request by WHO MS to assess the quality, safety and efficacy of low-cost and new FDCs HIV/AIDS generic medicines PQ beginning: 2001 Vaccines Origin: Request by UNICEF and PAHO to evaluate quality, safety and efficacy of vaccines in the context of national immunization programmes PQ beginning: 1987

5 5 Background Today, the prequalification team is responsible for the qualityassurance of IVDs, MCDs, FPPs, APIs, QCLs, vaccines and immunization devices Diagnostics (Dx) assessment of in-vitro diagnostics (IVDs) & male circumcision devices (MCDs) Medicines (Rx) assessment of finished pharmaceutical products (FPPs) & active pharmaceutical ingredients (APIs) Vaccines (Vx) assessment of vaccines & immunization devices (ImDs) Laboratory evaluation & testing of Dx, Rx & Vx Inspections of manufacturing sites & Technical assistance to manufacturers, NRAs and other stakeholders Laboratory prequalification of Rx quality control laboratories (QCLs) Facilitation of National regulatory approval for Dx, Rx & Vx

6 VCPAG

7 Overview of the PQT grant Objectives Key activities 1 Improve quality and efficiency of vector control assessment Create and staff vector control assessment group within PQT based on model of other PQT groups and WHOPES Develop quality assessment systems for vector control products 2 Assist NRAs to optimize national registration times Identify and engage NRA contacts and pilot collaborative registration 1 procedure 3 Develop a sustainable PQT model Determine fee structure / funding model for vector control evaluation in PQT 4 Prequalify and maintain prequalification status of vector control products Conduct assessments of vector control products in PQT system as of 1/1/17, including quality, safety, and efficacy assessments Conduct post marketing quality inspections of manufacturing sites and finished products based on risk assessment protocols 5 Communicate with stakeholders to build strong trust in WHO prequalification systems Engage with relevant stakeholders to communicate changes in WHO vector control evaluation system, and build strong trust is WHO prequalification systems 1. Collaborative procedure with NRAs to facilitate the assessment and accelerated national registration of WHO-prequalified products

8 8 Key numbers Through the prequalification process, WHO has made available numerous quality-assured products to WHO Member State markets As of October 2016: 42 QCLs Medicines 415 FPPs 94 APIs Diagnostics 62 IVDs 2 MCDs Vaccines 145 Vx

9 9 Key successes WHO prequalification has also raised awareness of the importance of quality-assurance of health products in resource-limited settings, made available and facilitated the uptake of new products Common achievements Creation of awareness of quality issues to regulators, manufacturers and procurers Building of NRA capacity and regulatory harmonization Improvement of manufacturers GMP status and QMS Development and implementation of quality policies with procurement agencies Development of a robust mechanism applicable to different types of products and diseases Adaptation to the needs of stakeholders Creation of a sustainable and affordable market of quality-assured products

10 Vaccines Medicines Diagnostics 10 Key successes WHO prequalification has also raised awareness of the importance of quality-assurance of health products in resource-limited settings, made available and facilitated the uptake of new products Common achievements Advocating for medical devices regulation in countries Creation of Prequalification awareness of quality of point issues of care to devices regulators, manufacturers and procurers Building of NRA capacity and regulatory harmonization Improvement Bringing of manufacturers confidence GMP to the status quality and of generics QMS Development Introduction and implementation of the prequalification, of quality policies hence quality-assurance with procurement agencies of ARV monotherapies, FDCs and APIs Development of a robust mechanism applicable to different types of products and diseases Adaptation to the needs of stakeholders Establishment of prequalification as the sole quality-assurance Creation of a mechanism sustainable international and affordable donor-funded market of procurement quality-assured products

11 11 WHO prequalification of in-vitro diagnostics, medicines and vaccines Outline Introduction Prequalification role Prequalification process Supporting activities and procedures Conclusion

12 Goal 12 Goal, strategy & outputs The mission of WHO prequalification is to ensure timely availability of quality-assured health products for the prevention, diagnosis and treatment of priority diseases in low- and middle-income countries Make quality priority products available in a consistent and timely manner Ensure sustainable supply of quality-assured products Create national capacity to evaluate and monitor the ongoing quality of products Strategy Apply and promote unified quality, safety and efficacy/performance standards, for a comprehensive evaluation of health products Build the capacity of staff from NRAs, QC labs, manufacturers or CROs Key outputs List of prequalified products and QCLs WHO public reports Accelerated national registration of prequalified products Increased regulatory capacity at national level Improved GMP and QMS

13 13 Added-value WHO prequalification assesses the quality, safety and efficacy/performance of health products, while focusing on the specific needs of resource-limited settings Unique PQ characteristics Programmatic suitability: specific emphasis on issues of particular relevance to resource-limited settings, such as: Stability of products (heat conditions) Adapted specimen type (Dx)/ formulation (Rx)/ presentation (Vx) Labelling of products Ease of use (in terms of training and material) Efficacy/performance evaluated in the global population Life cycle management of products Strengthening manufacturers and NRAs capacity

14 Vaccines Medicines Diagnostics 14 Added-value WHO prequalification assesses the quality, safety and efficacy/performance of health products, while focusing on the specific needs of resource-limited settings Unique PQ characteristics Focus on the versions of products that have not been stringently assessed (RoW versions) Programmatic Risk suitability: classification specific rules applied emphasis with on a issues focus on of particular RLS, therefore relevance the to resource-limited stringency settings, of the such review as: is determined differently Stability of products (heat conditions) Adapted Prequalification specimen type (Dx)/ of APIs formulation and QCLs (Rx)/ presentation (Vx) Labelling Participative of products process: significant involvement of regulators for lowand middle-income countries Ease of use (in terms of training and material) Efficacy/performance evaluated in the global population Life cycle management Assessment of of NRA products functionality Strengthening Prequalification manufacturers of immunization and NRAs capacity devices

15 15 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

16 16 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 Faster regulatory approval Timely assessment of variations and changes 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

17 17 WHO prequalification of in-vitro diagnostics, medicines and vaccines Outline Introduction Prequalification role Prequalification process Supporting activities and procedures Conclusion

18 18 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 Screening CAPA Assessment Inspection Follow-up inspection CAPA Prequalification decision

19 19 Prequalification workflow such as the pre-submission form and laboratory evaluation for in vitro diagnostics Pre-submission form Dossier submission Screening CAPA Assessment Lab evaluation Inspection Follow-up inspection CAPA Prequalification decision

20 20 Prequalification workflow or NRA functionality and programmatic suitability for vaccines Dossier submission Screening NRA functionality Programmatic suitability CAPA Assessment Inspection Follow-up inspection CAPA Prequalification decision

21 21 Prequalification workflow In addition, SRA-approved products are evaluation according to the abbreviated prequalification procedure Information package submission Screening NRA functionality Programmatic suitability Review of SRA evaluation documents Assessment Lab evaluation Inspection Verification of GMP/QMS status Prequalification decision

22 22 Product eligibility Based on WHO Member States needs, WHO disease programmes set eligibility criteria and determine priorities for prequalification Diagnostics IVDs and MCDs HIV, HCV, HBV, Malaria RDT, HPV POC, G6PD IVDs Abbreviated assessment IVDs only Stringently assessed SRA-approved products & their RoW version if no substantial difference Medicines FPPs and APIs HIV/AIDS, HBV, HCV, Tuberculosis, Malaria, RH, Influenza, Diarrhoea, and NTDs EOI Priority criteria for evaluation Abbreviated assessment FPPs and APIs SRA-approved Vaccines Vaccines & immunization devices 24 priority diseases Eligibility criteria for evaluation, including NRA functionality Priority criteria, including fast-track procedure Abbreviated assessment Vaccines only SRA-approved

23 23 Standards & guidelines WHO prequalification exemplifies application of best international practice as the basis for evaluation and adapts the use of existing standards and guidelines to serve the specific needs of RLS Best international practice Validated international standards and guidelines, with a focus on the needs of RLS WHO guidance Examples Diagnostics ISO, IMDRF, GHTF, CLSI, WHO standards, guidelines and guidance Examples Medicines & Vaccines GMP International pharmacopoeia Performance specifications WHO quality and interchangeable guidelines for generic products Technical report series

24 Triggered Systematic 24 Post-PQ activities Ensuring the ongoing quality of prequalified products is an equally important responsibility of the prequalification team Post-PQ validation Post-marketing surveillance Annual report review Reinspection Requalification Sampling & testing Variations/changes assessment Adverse event monitoring

25 25 WHO prequalification of in-vitro diagnostics, medicines and vaccines Outline Introduction Prequalification role Prequalification process Supporting activities and procedures Conclusion

26 Principles 26 Collaborative procedure The collaborative procedure enables NRAs to accelerate the registration of prequalified products so that they can enter local markets more quickly WHO PQ shares the reports that served as the basis for the prequalification decision, so that NRAs do not conduct assessment and inspections National registration based on PQT evaluation Diagnostics Procedure in development Ongoing discussions with NRAs Medicines Started in 2012 As of July 2016: 28 countries participating 165 registrations in 19 countries for 65 different products Vaccines Procedure published in 2007, harmonized for medicines and vaccines as of 2014 In 2015: Adopted by expert committee (ECBS)

27 27 Other quality-assurance procedures Complementary procedures exist to identify products for which public health need is great but few or no quality assured products are available for procurement Expert Review Panel (ERP) for medicines or diagnostics Regular assessment of the potential risks/benefits associated with the procurement of products that have a high public health impact, but have not yet undergone a stringent assessment, either by WHO Prequalification or by another SRA Eligibility Product under assessment by WHO PQ or an SRA, or commitment from the manufacturer to submit to one of these (Dx only) GMP/QMS compliant Procedure Coordinated by WHO, twice a year Review of available data on quality, safety and efficacy/performance of products by external experts

28 28 Other quality-assurance procedures Complementary procedures exist to identify products for which public health need is great but few or no quality assured products are available for procurement Emergency Use Assessment and Listing (EUAL) Emergency quality assessment in order to expedite the availability of IVDs, medicines or vaccines needed in the context of a Public Health Emergency of International Concern Eligibility Public Health Emergency of International Concern No comprehensive pre-market regulatory assessment undertaken Manufactured in compliance with GMP/under functional QMS Applicant commits to complete the development of the product and apply for WHO prequalification Procedure Review of a simplified dossier, including QMS for diagnostics Laboratory evaluation (Dx only) Abbreviated EUAL assessment possible

29 29 Capacity building & support The prequalification team also builds manufacturing and regulatory capacity and provides technical assistance to produce and regulate quality assured products Capacity building Trainings & workshops to regulators, mfr, CROs and laboratories Participation of regulators in assessments and inspections as observers or rotational fellows Joint WHO-NRA assessments Joint NRA reviews of WHO assessments Technical support Technical assistance to mfr, laboratories, procurers (including UN) and WHO MS Scientific advice to mfr Programmatic advice to mfr Target product profiles Guidance Guidelines on PQ processes for mfr Model/sample dossier Q&A documents Guidance notes for NRAs Guidance notes for procurers

30 30 Capacity building & support The key objective of technical assistance is to facilitate prequalification of priority medicines/diagnostics Provision of consultants to advice on GMP or GCP compliance Data development and compilation of dossier Assistances are separated from the assessment / inspections Assistances may include specific trainings Assistance is provided in principle free of charge

31 31 Contacts Prequalification team Deus Mubangizi PQT Coordinator Diagnostics Irena Prat Medicines Matthias Stahl Vaccines Carmen Rodriguez Hernandez Inspections Deus Mubangizi Technical assistance & laboratories Milan Smid

32 32 Outline Annexes

33 Prequalified FPPs Sep HIV/AIDS MA TB RH IN NTD DI

34 APIMF/API PQ Applications 100 APIMFs accepted through APIMF procedure vs APIs Prequalified - since APIMF API PQ

35 WHO collaborative registrations Participating NMRAs 1 medicines registered 1 EOIs/submissions received No EOIs yet As at 19 September 2016

36 Established acceptance by manufacturers and NMRAs Total registrations: 162 (As at 19 September 2016) 36

37 Country (when started): submissions Pipeline of applications in countries No products registered or under review yet: Georgia, Lao PDR, Sierra Leone, Zanzibar As at 19 September

38 Time to registration ( to date, n=162) Including regulatory time and applicant time As at 19 September