Transcript Meek - Lessons learnt from the Ebola outbreak

The Ebola Outbreak
Lessons Learned
& Pathways for Approval for Emergency Use of Medical products
3rd Annual Regulatory Workshop NEW DEVELOPMENTS IN DRUG REGULATION
8 - 9 September, 2015
Independent review of WHO Activities
in EVD outbreak
• Ebola Interim Assessment Panel – Report of July 2015
• WHO Response Outline – August 2015
• http://www.who.int/csr/resources/publications/ebola/ebola-panelreport/en/
Three Broad Areas Identified for improvement
• Review and Strengthen International Health Regulations
• Improve co-operation with broader health and
humanitarian systems
• Increase WHO’s emergency response capacity
Emergency Response Capacity
• Recommendations include:
• WHO should play a central convening role in acceleration of
development of appropriate diagnostics, vaccines, therapeutics
and medical and information technology
Ebola candidate vaccines
• rVSV ZEBOV (Merck/Newlink).
• ChAd3 ZEBOV (GSK)
• Ad26.ZEBOV/MVA BN Filo Prime Boost Prophylactic Ebola Vaccine
Regimen (Janssen)
• Ebola/Makona Glycoprotein (GP) Nanoparticle Vaccine (Novavax)
WHO Involvement in Ebola vaccine R&D
• Facilitated the initiation of the phase I of VSV vaccine, in Europe
(Hamburg and Geneva) and in Africa (Gabon and Kenya)
• Joint review of clinical trial protocols – collaboration between AVAREF
and WHO/RSS (with the support from Health Canada, US FDA, EMA,
and several member states)
• Sponsored VSV vaccine Phase III CT (Ring vaccination) + in parallel
study involving Frontline Workers in Guinea
• Summits convened
From R&D to Regulation - Challenges
• Difficulty in obtaining efficacy data in face of declining case numbers
• No immunological correlate of protection established
• Validation of ELISA methods for measuring immunogenicity still in
progress
• Data requirements for registration
• Acceleration of regulatory review
WHO Emergency Use Assessment and Listing
• EUAL guidance development initiated in response to Ebola outbreak
• Scope includes potential future outbreaks of other diseases
• Developed for three product streams currently in scope of WHO
prequalification programme:
• Vaccines
• Pharmaceuticals
• In-vitro diagnostics
• http://www.who.int/medicines/news/public_consult_med_prods/en/
EUAL – WHY?
• Provides framework for review in emergency
context
• To guide UN procurement decision-making
• To assist highly impacted countries in their
regulatory decision-making
EUAL - ELIGIBILITY
• Declared Public Health Emergency of International Concern (PHEIC) by the
WHO Director-General
• Lack of routine marketing authorization for type of product or supply
shortage
• Manufactured in accordance with GMP standards
• Attestation from producer of intention to complete development and apply
for WHO prequalification
• [for vaccines] Manufactured in a country whose NRA has been assessed as
functional for vaccine regulatory oversight by WHO.
• WHO may consider reviewing a candidate vaccine for EUAL that does not
meet all of the above requirements
EUAL is not Prequalification
• Specific procedure under circumstances of a public health emergency for
time-limited approval for use.
• Principles of data requirements for each product type identified in the
respective guidance document. Applicants are highly encouraged to
contact WHO as early as possible during development to discuss specifics
of their application.
• Abbreviated review where some emergency use authorisation granted by
an NRA.
EUAL – APPLICATION CONTENT – VACCINE EXAMPLE
• Manufacturing Quality Data
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Cell and seed bank characterisation
Justified methodologies and specifications
Process validation
Evidence of GMP compliance
Stability data
• Programmatic characteristics not acceptable for PQ may be allowed
for EUAL
EUAL – APPLICATION CONTENT – VACCINE EXAMPLE
• Non-clinical Data
• Demonstrating acceptable safety, immunogenicity, and efficacy in the most
appropriate animal model
• If the non-clinical package is not complete at the time of submission, the applicant must
submit adequate justification for the lack of complete data and a plan and timeline for
submitting those data
• Clinical data
• Demonstrating acceptable safety, immunogenicity, and efficacy, if available
• If it is not possible to obtain efficacy data, the applicant will have to demonstrate that
immunogenicity data are sufficient under the circumstances.
• A plan to monitor quality, safety, and efficacy in the field and to
submit the new data as soon as possible to WHO.
EUAL - DECISION
• WHO public report will be made available on the WHO website.
• The validity of a listing will generally be for 12 months.
• Can be reviewed and extended if necessary.
• Can be extended beyond the PHEIC (stockpile)
• Decisions will also be reassessed if further data become available that
could alter the original opinion.
Have products received an EUAL?
• In- vitro diagnostics:
• Altona Diagnostics GmbH
• RealStar® Filovirus Screen RT-PCR Kit 1.0
• Corgenix Medical Corporation
• ReEBOV™ Antigen Rapid Test Kit
EUAL of IVDs challenges encountered in Ebola outbreak
• Larger manufacturing base (but many inexperienced)
• Poor technical documentation and Quality System
• Submission before design finalisation
• Difficulties in clinical performance testing
• Lack of standard preparations
• Target of test kit - inadvertent detection of post-vaccine
circulating antigen or nucleic acid
• Fraudulent claims
Next steps - EUAL
• Ad hoc Advisory Committees for the Emergency Use of Products will
be established where required as part of the review process for
applications for EUAL
• Implementation of collaborative procedure between WHO PQ and
regulators from affected countries: Joint review
Next steps – more broadly
• Develop blueprint for research preparedness for future disease
preparedness
• Review and revision of IHR
• Development of global health emergency workforce
Thank you