WHO vaccine standardization: an update

Transcription

1 PDVAC WHO vaccine standardization: an update Dr, WHO/HIS/EMP/TSN/NSB 10 th June 2016 Geneva

2 Outline Standardization and regulatory evaluation of vaccines and biotherapeutic products Development of measurement and written standards Standards adopted by the ECBS 2015 Plan for 2016 and 2017 Selected topic: Revision of guidelines on clinical evaluation of vaccines Standardization of RSV vaccines

3 WHO norms and standards for biologicals Global written standards Total 86 docs (Recommendations/ Guidelines) General docs that apply to both vaccines & BTP: 9 General documents that apply to all vaccines: 10 Vaccine specific: 60 BTP specific: 7 Scientific evidence 1) Standardization of assays 2) Further development and refinement of QC tests 3) Scientific basis for setting specifications Global measurement standards Measurement standards: essential elements for development, licensing and lot release

4 Role of WHO WHO is a specialized agency of the United Nations system Not a regulatory agency Key role in ensuring global availability of vaccines and biologicals of assured quality Setting global norms and standards and promoting their implementation WHO assessment and regulatory capacity building of National Regulatory Authorities WHO prequalification

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6 ECBS 2015: Reference Preparations established for vaccines 3 rd International Standard for Diphtheria Toxoid for Flocculation Test 1 st International Standards for Meningococcal serogroup A and X polysaccharides 1st International Standard for anti-ev71 antibodies. 1 st International Reference Reagent for Ebola antibodies 1 st International Reference Reagent for Ebola NAT (Ebola virus RNA) New Work agreed IS for meningococcal serogroup W and Y polysaccharides : antibodies (human) to Clostridium difficile

7 New Guidance documents adopted by the 66th WHO Expert Committee on Biological Standardization (ECBS) Title Brief description WHO Guidelines on Good Manufacturing Practices (GMP) for Biological Products (Revised) WHO Guidelines on Stability Evaluation of Vaccines for use under Extended Controlled Temperature Conditions (New) WHO Recommendations to assure the Quality, Safety and Efficacy of Recombinant Human Papilloma Virus-like Particle Vaccines (Revised) Regulatory assessment of approved rdna-derived biotherapeutics, Addendum to: WHO TRS 987, Annex 4 (New) Major revision. Biocontainment now included for products like poliovirus vaccines. Describes stability evaluation of a specific vaccine when exposed to a planned short term temperature excursion outside the cold chain immediately prior to administration. Avoids off-label vaccine use. Revision covers use of immunological endpoints; development of HPV vaccines with extended valency; plus likely entry of new products into the market. Regulatory assessment of biotherapeutics licensed with data that do not comply with current international regulatory standards for biotherapeutic products including biosimilars.

8 Timeline for WHO Written Standards: Vaccines IPV Post-app. Changes RA for AAs GMP HPV ECTC Clinical Flu label Pregnant Flu non-producing Ebola IPV- safe production RSV Others DTP MAL TPH TPH Informal consultation ECBS submission Implementation workshop

9 Written Standards under development: plan for submission to ECBS in 2016/ 2017 Guidelines on clinical evaluation of vaccines (revision of TRS 924, annex 1, adopted by the ECBS in 2001) Guidelines on influenza vaccines for non-producing countries (new) Maternal immunization - Guidelines on labelling influenza vaccines for use in pregnant women (new) Guidelines on quality, safety and efficacy of Ebola vaccines (new) Guidelines on safe production and quality control of inactivated polio vaccines (revision of TRS 926, annex 2, adopted by the ECBS, 2003) Guidelines on Monoclonal antibodies developed as Similar Biotherapeutic Products (new)

10 Clinical evaluation of vaccines revision of Guidelines published in TRS 924, annex 1 Since the adoption of Guidelines in 2001, more than 20 vaccine specific documents with clinical section were published Consultation with regulators, manufacturers and other experts held in July 2014 (meeting report published - Vaccine 33 (2015) ) Drafting group prepared updated version which was subject of 2 rounds of public consultation (Nov 2015 and Feb - March 2016) Main changes Working Group meeting on 3 rd May 2016 Next steps: further revision and 3 rd round of public consultation (July Sep 2016) Submission to the ECBS for review in Oct 2016

11 Structure of revised Guidelines on clinical evaluation of vaccines Introduction Scope Glossary Vaccine Clinical Development Programs Immunogenicity Efficacy and effectiveness Safety Authors and Acknowledgements References

12 Working Group meeting on 3 rd May 2016 Comments received during the 2 nd round of public consultation (15 Feb to 15 March 2016) were incorporated into the updated draft Guidelines before the WG meeting Review of key issues in the updated version of clinical guidelines A number of clarifications and improvements were proposed in the context of CT design, immunogenicity, efficacy and effectiveness and safety Additional points: vaccine trials registries, immunization of pregnant women, evaluation of pain due to vaccine injection List of topics for implementation workshops

13 Revision of clinical guidelines (TRS 924) proposed new definition of immunological correlates of protection (ICP) An ICP defined as a type and amount of immunological response that correlates with vaccine-induced protection against a clinically apparent infectious disease and is considered predictive of clinical efficacy For some types of vaccines the ICP may be the type and amount of immunological response that correlates with vaccine-induced protection against infection (e.g. hepatitis A and B vaccines) The ICP may be: mechanistic (i.e. causative for protection, such as antibody that effects virus neutralization or serum bactericidal antibody) or non-mechanistic (i.e. non-causative, an immune response that is present in those protected by vaccination, but not the cause of protection (such as serum IgG against VZV in the context of prevention of herpes zoster)).

14 Human challenge trials (HCT) Brief information intended to raise awareness among regulators that these trials are usually conducted during the early clinical development of vaccines and some of these data may become part of the data submitted to NRAs Purposes for conducting HCT are provided but the examples would help illustrating different scenarios Proposed as an Appendix to the Clinical Guidelines but the Working Group meeting on 3 rd May 2016 led to the conclusion that it's better to have a separate web-based document Different practices with respect to the authorization of HCT in different countries

15 Standardization of RSV vaccines 1. Written: Guidelines for clinical evaluation of vaccines revision ongoing Guidelines to assure quality, safety and efficacy of RSV vaccines project is planned to start in 2017 Clinical evaluation of RSV vaccines review in Q Measurement standards - IS 3. Standardization of the assays: Manual/ and or SOP 4. Training: - needs to be identified at the later stage

16 Design of collaborative study for RSV serology IS Purpose of IS: To support development of vaccines To make results from clinical trials more comparable Additional potential use: sero-epidemiology Top priority: various VN assay formats, adult serum samples Potential future considerations: Other assays Monoclonal antibody competition assay (palivizumab) Paediatric samples

17 Many thanks for continuous input and advice to: Members of WHO drafting and Working Groups Collaborating Centers Many individual experts

18 Thank you Further information and contact Biological standardization website: Contact details: Dr (