The Ebola OutbreakLessons 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 Activitiesin EVD outbreak

• Ebola Interim Assessment Panel – Report of July 2015

•WHO Response Outline – August 2015

• http://www.who.int/csr/resources/publications/ebola/ebola-panel-report/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 • 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