Regulatory Preparedness to address Public Health Emergencies

Carmen Rodriguez

Vaccines assessment PQ

Regulation of Medicines and other

Health Technologies (RHT)

Context (1)

Regulation and other health technologies (RHT) aims to strengthen

regulatory preparedness for public health emergencies through:

1. Strengthening of regulatory procedures for risk-based evaluations

during public health emergencies (PHEs)

2. Reinforcing RHTs capacity to support regulatory preparedness for

PHEs

3. Assist countries in adapting their regulatory requirements for PHEs

and using networks for expedited assessments during PHEs

WHO regulatory work in Public Health Emergencies

Support for WHO’s R and D Blueprint

Technical guidelines and standards

Regulatory Systems Strengthening - preparedness

Emergency Use Assessment and Listing (EUAL)

Safety monitoring

Communication and coordination

Challenges and lessons learnt

3

Technical Guidelines and Standards

Guidelines on the Quality, Safety and Efficacy of Ebola Vaccines

• Product specific guidelines on development, production, quality control and

evaluation (prior to licensing)

• Intended to facilitate progress towards licensing

• The guidelines do not discuss regulatory pathways for approving investigational

vaccines for use in public health emergencies. These pathways are often NRA

specific and the issue is being addressed separately

• Endorsed at ECBS in October 2017 – Published May 2018

• Implementation workshop planned Q1 2019

• 7 WHO international Ebola reference standards developed

4

Next meeting of the ECBS (1): 29 Oct – 2 Nov 2018

NEW: “Nucleic acid based vaccines of importance for priority pathogens for PHE”:

• Revision of guidelines for DNA based vaccines

• Points to consider on RNA based vaccines

5

4th meeting of the CC network on vaccines: Sep 2018

Will be hosted by the NIFDC in China

CC meeting, Beijing, 13- 14 Sep 2018

Symposium on new vaccines on 12th Sep 2018 in Beijing

3 main themes:

• Focus of measurement standards and the input from CC network to the ECBS – procedure and examples

• Revision of TRS 932, Annex 2 (dengue vaccine)

• Standardization of priority pathogens

Mapping of emergency provisions using

Global Benchmarking Tool (GBT) 40 countries benchmarked

Afghanistan Gambia Malaysia Somalia

Bangladesh Guinea-Bissau Maldives South Sudan

Bhutan India Mongolia Sri Lanka

Burundi Indonesia Mozambique Sudan

Cambodia Islamic Republic of

Iran Nepal Syrian Arab Republic

Cape Verde Kazakhstan Niger Thailand

China Kenya Pakistan Timor-Leste

Egypt Lao People's

Democratic Republic Papua New Guinea Uganda

Eritrea Lebanon Saudi Arabia United Republic of

Tanzania

Ethiopia Liberia Serbia Viet Nam

6

AVAREF Table top exercise: Nov 2017, Ghana

• Table top based on hypothetical case study presenting a request to trigger

AVAREF joint review process for a candidate vaccine and for performance

evaluation of candidate in vitro diagnostics

• Exercise organized by WHO and NEPAD with the support of Coalition for

Epidemic Preparedness Innovations (CEPI) and BMGF and involvement of

other partners including:

• European and Developing Countries Clinical Trials Partnership (EDCTP)

• US FDA

• Paul Ehrlich Institute (Germany)

• The AVAREF joint review guideline was validated as fit for purpose as a result

of the exercise

• A series of recommendations were made to AVAREF on further improvements

to the Guideline and the broader issues identified by the group

7

Emergency Use Assessment and Listing (EUAL)

Following 2014 Ebola outbreaks in Africa, WHO introduced EUAL procedures to

expedite the availability of medical products needed in PHEIC

Procedures for candidate Vaccines, Diagnostics and Therapeutics published 2015

1. Intended to be used both for UN procurement decision-making and to support highly impacted

countries in their regulatory decision-making

2. EUAL is not prequalification, but a time limited procedure – essentially a risk based approach

3. Rolling review based on review of data by external experts

4. Listing under EUAL is based on eligibility criteria, a set of quality, safety and efficacy data and

benefit-risk assessment

5. Inclusion in the EUAL should not compromise the clinical development of the product

8

EUAL status as of June 2018

9 diagnostics evaluated (7 Ebola, 2 Zika)

3 applications for vaccines (Ebola)

No therapeutics defined as eligible

• OraQuick® Ebola Rapid Antigen Test Kit (Cadaveric Oral fluid and

Whole Blood)

• SD Q Line Ebola Zaire Ag

• FilmArray™ Biothreat-E

• Xpert® Ebola Test

• Liferiver™ - Ebola Virus (EBOV) Real Time RT-PCR Kit

• ReEBOV™ Antigen Rapid Test Kit

• RealStar® Filovirus Screen RT-PCR Kit 1.0

9

Ebola EUAL for IVDs

25 applications received and 7 IVDs listed

Challenges

• Major difficulties with access to

specimens and standards

• Ethical clearance: procedures

and timelines

• Submissions quality: poor

validation data

• Post-listing changes

management and PMS

• WHO resources (staffing)

10

Successes

• Great collaboration with affected countries

and partners, particularly in Sierra Leone:

EU Mobile Lab (Hastings), Nigeria Mobile

Laboratory (Kambia), PHE Laboratories

(Kerrytown, Port Loko, Makeni), Bernhard

Nocht Institute for Tropical Medicine

(Hamburg, Germany)

• Collaboration (abridged assessment) with

USFDA

• Assessment funding secured through BMGF

Experience with Ebola EUAL for IVDs

Consultation held in March 2016:

– 15 organizations + WHO;

– Requirements for technical documentation, and;

– Performance evaluations protocols.

11

Zika EUAL for IVDs

33 applications received and 4 IVDs listed

• AccuPower® ZIKV (DENV, CHIKV) Multiplex Real-Time RT- PCR Kit;

• RealStar® Zika Virus RT-PCR Kit 1.0;

• Liferiver Zika Virus (ZIKV) Real Time RT-PCR Kit, and;

• careGENE™ Zika Virus RT-PCR kit.

12

Successes

• Established process for requirements

setting • Support to requirements setting

process from 15 organizations

• Collaboration with IP in French Guyana • International cooperation on dossier

assessments

• Collaboration (abridged assessment)

with USFDA

Experience with Zika EUAL for IVDs

Challenges

• Lack of support for EUAL performance

evaluations; promised work not delivered

• Major difficulties with access to

specimens and standards

• Ethical clearance: procedures and

timelines

• Submissions quality: poor validation data

• Post-listing changes management and

PMS

• WHO resources (staffing)

Experience with EUAL for Merck

WHO-AVAREF meeting: 21-22 June 2018, Geneva

• Regulators from Burundi, CAR, Congo, Ghana, Nigeria, South Africa,

Tanzania, Uganda, and Zambia and representatives from WHO AFRO met

in Geneva to review and discuss key regulatory considerations required to

facilitate implementation of EUAL for Ebola vaccine in an emergency

• Role and input of AVAREF discussed –potential for joints review

• All countries indicated that they had specific provisions allowing use of an

EUAL in emergency situations

• General recommendations and specific recommendations for concerned

member States, AVAREF and WHO were developed

• Principles and guidance to be further developed

13

Revision of EUAL: Principles

• A pre-emergency phase to concentrate most of the assessment activities and allow a rapid

decision when the emergency (PHE) is declared and a post deployment monitoring phase

• Involvement of NRAs responsible for oversight of the products and NRAs of potentially affected

countries at different stages of the procedure

14

Pre-emergency phase: • Establishment of an assessment platform and better definition of eligibility criteria

o Agreements with NRAs of record for information sharing

o Framework for interaction with NRAs and Expert committees of potentially affected countries

o Roster of experts

o Establishment of Committees:

• Product Evaluation Committee (PEC)

• Ad-Hoc Committee for Emergency Use Listing (ACEUL)

• Assessment by PEC

Where do we need to do more work?

Safety monitoring • Roles and responsibilities, what needs to be collected and who needs to do it? Post

listing change management and surveillance

Communication and coordination • In an emergency, all bets are off, regulators need a seat at the table

Challenges and lessons learnt • Poor understanding of EUAL process

• Lack of data, difficulties with access to specimens and standards especially for IVDS

• WHO resources (staffing)

15

www.who.int

Thank you