Learning from Past Emergency Use Authorizations

Transcription

1 Learning from Past Emergency Use Authorizations Elliot P. Cowan, Ph.D. Principal, Partners in Diagnostics, LLC PDC Workshop on New and Innovative Approaches to Laboratory Diagnosis of Zika, Dengue and other Arboviruses Fondation Mérieux, Annecy, France 2 May 2017

2 Objectives of this Talk How to reconcile the need for regulatory oversight of IVDs vs. critical need in an emergency situation. Identify lessons learned from how Ebola and Zika IVDs were/are being brought to use through the FDA Provide resources to aid in bringing tests forward 2

3 BACKGROUND 3

4 Conventional Approach to Regulation 4

5 Regulation in the Context of a Public Health Emergency 5

6 Expected Regulatory Benchmarks CONVENTIONAL: PUBLIC HEALTH EMERGENCY: REASONABLE ASSURANCE OF SAFETY AND EFFECTIVENESS IN THE SHORTEST POSSIBLE TIME 6

7 Global Response to Assess IVDs in a Public Health Emergency Emergency Use Authorization (EUA) Emergency Use Assessment and Listing (EUAL) 7

8 EUA vs. EUAL EUA EUAL Requires declaration of an emergency situation Yes Yes Review of technical documentation relating to safety and performance Review of the documentation relating to manufacturer s quality management system Independent laboratory evaluation of product s performance and operational characteristics Limited data No No Limited data Yes Yes Time-limited authorization for use Yes Yes Review timeframe Hours to Days Not specified Adverse event monitoring/reporting Yes Yes 8

9 LESSONS LEARNED 9

10 Lessons Learned #1 It can be very difficult for test developers to have access to specimens. Typically in short supply Ethical issues Political issues Logistical/safety issues Biosafety issues: Insufficient BSL 4 facilities for Ebola As a result: Ebola panels came too late Many more commercially available, characterized Zika panels than Ebola panels BARDA/FDA panels made quickly 10

11 Role of Panels in Product Development 11

12 Lessons Learned #2 Test development requires a very steep learning curve. What is the biology of the infection? How transmitted? Type of specimen? Chronology of infection? How long does virus persist? What to detect? NAT: Target? Antigen: Target? Antibodies: IgM? IgG? Intended use? Aid in diagnosis? Screening? 12

13 Lessons Learned #3 Information sharing is critical among all stakeholders to ensure needs are addressed. Public health agencies Within countries (e.g., FDA, CDC, BARDA) Globally (WHO, affected countries) Strain on public health facilities if require follow up testing Regulatory agencies Test developers (to the extent possible) Public CDC doing a good job with Zika informing public of preventive measures, risk in pregnancy. Ebola characterized by panic Establish agreements to facilitate information exchange 13

14 Lessons Learned #4 Procedures are needed to enable efficient acceptance and implementation of emergencyuse tests. Insistence on candidate test evaluation by countries delays implementation During Ebola crisis, countries were inundated by manufacturers of test kits that were of questionable quality 14

15 Lessons Learned #5 There are a number of factors that influence test development. Ability to make a test with acceptable performance (which is?) Ability to modify an existing testing platform as a starting point Prior experience dealing with emergency use Potential market 15

16 # OF TESTS AVAILABLE FDA Ebola and Zika IVD EUAs: Number of Tests Ebola Zika MONTHS AFTER EMERGENCY DECLARATION atoryandpolicyframework/ucm htm#current 16

17 # OF MFGS (NON-USG) FDA Ebola and Zika IVD EUAs: New Manufacturers Ebola Zika MONTHS AFTER EMERGENCY DECLARATION atoryandpolicyframework/ucm htm#current 17

18 # OF TESTS NAT vs. Serology NAT Serology 4 0 Ebola Zika 18

19 Ebola vs. Zika EBOLA ZIKA Mode of transmission Contact with body fluid Mosquito, sexual, transfusion, mother to child Detection Nucleic acid, antigen Nucleic acid, IgM [IgG?] Geographic distribution Limited to certain West African countries Brazil, multiple countries on CDC list, plus US Returning travelers everywhere Current status Rare Potential for rapid spread across US 19

20 Summary of Lessons Learned 1. Access to specimens is critical. 2. Time is of the essence: Test development requires a very steep learning curve. 3. Information sharing is critical. 4. Procedures are needed to enable efficient acceptance and implementation of emergency-use tests. 5. Test development is influenced by a number of factors, likely strongly by potential market. 20

21 Lessons Learned from Lessons Learned All emergencies are not the same. Act accordingly. Keep learning. 21

22 Acknowledgements Sally Hojvat Formerly FDA/CDRH/OIR/DMD, now Partners in Diagnostics Uwe Scherf FDA/CDRH/OIR/DMD 22

23 EXTRA CREDIT!!! 23

24 For more information on EUA 24

25 FDA EUA Templates EMERGENCY USE AUTHORIZATION DRAFT INTERACTIVE REVIEW TEMPLATE FOR SEROLOGICAL IgM ASSAYS (ZIKA VIRUS SPECIFIC) EMERGENCY USE AUTHORIZATION DRAFT INTERACTIVE REVIEW TEMPLATE FOR MOLECULAR ASSAYS (ZIKA VIRUS SPECIFIC) 25