Regulation of H1N1 Pandemic Influenza Vaccine

1. April 8, 2010Montreal Forum Pharmaceutical DiscussionsStephanie HardyOffice of Policy and International CollaborationBiologics and Genetic Therapies DirectorateHealth Products and Food Branch Regulation of H1N1 Pandemic Influenza Vaccine

2. Outline • Traditional path for vaccine licensure • Key challenges for pandemic vaccines • Regulatory preparedness • Surprise…H1N1! • International collaboration • Regulatory pathway • Conclusions and next steps

3. Traditional Path for Vaccine Licensure • Research & development • Clinical trials (Phase I, II, III studies) • Regulatory evaluation and market authorization • Post marketing lot release and surveillance for adverse events Traditional vaccine development and approval processes can take up to 7 years, with large clinical trials conducted prior to approval Clinical trial applications New Drug Submission Notice of Compliance & Drug Identification Number issued

4. Pandemic Vaccines: Key Challenges • Time Issue • Vaccine cannot be developed until pandemic strain isolated • Vaccine production takes a minimum of 5 months • Vaccine likely needed immediately upon manufacture • No or limited time for traditional clinical trials

5. Pandemic Vaccines: Key Challenges • Key regulatory challenge: • Mechanisms need to be in place that can be used to review and authorize a safe and efficacious vaccine for use in Canada, within the shortest time frame possible • If traditional processes used vaccine would not be available when needed • Global issuewhich called for proactive, global cooperation

6. HUMAN VACCINES FOR PANDEMIC INFLUENZA REGULATORY PREPAREDNESS WORKSHOPSWORKSHOP 1: Ottawa, 9-11 March 2006WORKSHOP 2: Bethesda, 12-13 June 2006WORKSHOP 3: Geneva, 14-15 June 2007

7. International Regulatory Preparedness Initiative • Created a global network of regulatory authorities engaged in pandemic influenza vaccine regulation • Resulted in joint development of regulatory guidelines - WHO Guidelines on Regulatory Preparedness for Human Pandemic Influenza Vaccines (2007) • Identified gaps/areas of regulatory uncertainty • Led to regulatory cooperation

8. Regulatory Preparedness • Emphasis placed on development and evaluation of “mock/prototype” vaccine • Focus was on H5N1 • Data showed need for 2 very high doses (90ug/dose) • Use of adjuvant reduced dose to 3.75ug/dose • “Antigen-sparing approach” considered useful given potential limited availability of vaccines and potential need for cross-protection

9. Regulatory Preparedness • Canada has contract with GSK for pandemic vaccine • Development and regulatory evaluation of a mock adjuvanted H5N1 vaccine was ongoing during the pre-pandemic period • Development of regulatory tools necessary to enable authorization of a pandemic vaccine was also ongoing

10. Surprise…H1N1! • Much different from mock vaccine • Will H1N1 behave similar to H5 or more like seasonal viruses? • Will one or two doses be needed? • Emergence of virus in March/April and closer to home than expected • Differs from assumptions made in pandemic planning – less time to respond

11. Changing Scenarios • Adjuvanted/unadjuvanted vaccines • Changing recommendations for pregnant women • Before September, it was unknown how H1N1 vaccine would behave and whether one dose would be immunogenic

12. Continued International Collaboration • World Health Organization • Biweekly teleconferences with influenza vaccine regulators • Continuation of network responsible for drafting WHO regulatory preparedness guidelines • Weekly safety surveillance teleconferences once vaccines were rolled out • Multilateral teleconferences • Core group to discuss broader regulatory issues (EMA-FDA-HC) • Clinical development sub-working group (EMA-FDA-HC) • Pharmacovigilancesub-working group (multiple regulators) • Agreement to share data amongst the regulators and public health agencies, both on immunogenicity and safety in real-time

13. Regulatory Pathway • The Food and Drugs Act and Regulations require that substantial evidence of clinical safety and effectiveness exist before a drug can be authorized in Canada. • However… • Actual pandemic strain much different from mock vaccine • Manufacturing began in June and vaccine was needed by Fall to prepare for second wave • No time for extensive clinical trials • Existing regulatory requirements could not be met

14. Regulatory Pathway • A set of new regulations needed to be written to allow for authorization of a pandemic vaccine based on limited rather than substantial clinical data, with commitment to provide additional information post-authorization • Interim Order

15. Regulatory Pathway • Interim Orders are issued by the Minister of Health under the authority of the Food and Drugs Act in rare situations where the Minister believes that immediate action is required to deal with a significant risk, direct or indirect, to human health, public safety, or the environment.

16. Vaccine Authorization • The adjuvanted vaccine (Arepanrix) was authorized on October 21, 2009 and the unadjuvanted vaccine was authorized on November 12, 2009 • Both vaccines were authorized under the provision of an Interim Order that was issued on October 13, 2009 and are indicated for active immunization against H1N1 influenza strain • Manufacturer must adhere to post-market commitments • A separate Interim Order was issued to enable immediate (emergency) access to limited quantities of unadjuvanted vaccine for pregnant women

17. Conclusions and Next Steps • H1N1 vaccine experience is a good example of how science and regulation are intertwined and how regulators have to respond to the challenge of balancing public safety/not inhibiting development and access to vaccines • Scientific and regulatory requirements had to be modified to address the uniqueness of the situation and to ensure that they enabled access to a safe and effective vaccine, within a short time frame • Success due in large part to pandemic preparedness efforts as well as collaboration and cooperation between national regulatory authorities, WHO and the manufacturer

18. Next Steps • Health Canada to continue working on longer-term regulatory pathways for pandemic vaccines and other emergency-use drugs • Extraordinary Use New Drug (EUND) Regulations • Pre-published in Canada Gazette, Part 1 on April 3, 2010

19. Next Steps • BGTD to conduct and participate in lessons learned activities and implement recommendations • BGTD to develop a guidance document on human pandemic influenza vaccines • To apply to manufacturers intending to file a submission to Health Canada for market authorization of a pandemic vaccine

20. Additional Information • Regulatory Authorization Documents – H1N1 vaccine • http://www.hc-sc.gc.ca/dhp-mps/prodpharma/legislation/interimorders-arretesurgence/index-eng.php • http://www.hc-sc.gc.ca/dhp-mps/prodpharma/legislation/interimorders-arretesurgence/index-fra.php • WHO Guidelines – Regulatory Preparedness for Human Pandemic Influenza Vaccines • http://www.who.int/biologicals/publications/trs/areas/vaccines/influenza/en/index.html • EUND Regulations, Canada Gazette, Part 1 • http://www.gazette.gc.ca/rp-pr/p1/2010/2010-04-03/pdf/g1-14414.pdf

21. Questions?