Norman W' Baylor, Ph'D',

1
2nd NVAC Workshop on Strengthening the Supply of
Vaccines in the U.S. Streamlining the FDA
Regulatory Process

• Norman W. Baylor, Ph.D.,
• Office of Vaccines Research and Review
• Center for Biologics Evaluation and Research
• U.S. FDA

2
NVAC Recommendations for Streamlining the
Regulatory Process

• Harmonizing content and format for regulatory
  submissions
• Review and implementation of cGMP standards
• Reviewing the regulatory process
• Conclusions

3
International Harmonization

• The FDA has made progress in information exchange
  using MOUs, and confidentiality agreements, e.g.,
  Health Canada, Paul Ehrlich Institute, TGA and
  the EMEA
• CBER/OCBQs deputy director has been assigned to
  a detail to Office of International Programs to
  expand MOUs to other vaccine regulators
• Notwithstanding, there are still some limitations
  due to different statutes (laws) and regulations

4
International Harmonization

• In September 2004, FDA announced it will apply to
  the Pharmaceutical Inspection Cooperation Scheme
  (PIC/S)
• Membership consists of inspectors/investigators
  from countries around the world
• Opportunity to discuss approaches, obtain
  information, harmonize
• CBER has been active in this area with respect to
  blood and blood products for many years.
• Expand to vaccines

5
Partnering With Foreign Regulators the Chiron
Experience

• Since MHRA license suspension October 5, 2004
• Meetings with MHRA and Chiron
• Ability to freely exchange information
• Regularly scheduled teleconferences between FDA
  and MHRA
• Observation of counterpart inspections

6
Review of GMP Standards

• Two-year agency initiative on pharmaceutical GMPs
  for the 21st century concluded September 2004
• Science and risk-based approach to review and
  regulation
• Implementation phase now underway with formation
  of council on pharmaceutical quality

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Review of GMP Standards Relevant Guidance to
Industry

• Scientific and technical cGMP formal dispute
  resolution August 2003
• Part 11 Computer system validation August 2003
• April 2004 federal register notice of intent to
  amend part 11
• Completion of GMP analysis in June 2004
• FDA intent to take incremental approach to
  modifications to parts 210/211 announced
  September 2004
• Quality system approaches to pharmaceutical cGMP
  September 2004
• Sterile drug products produced by aseptic
  processing September 2004

8
Team Biologics Program

• Development of systems-based compliance program
  for inspection of biological drug manufacturing
  facilities, including vaccines
• Implemented December 1, 2004
• Streamlined approach with levels based on
  compliance history
• Team biologics quality system
• CBER and ORA actively involved in establishing
  system of checks and balances (QC/QA)
• Metrics developed for many processes and in
  implementation phase
• Additional training for investigators and product
  specialists conducted in October 2004.

9
Reviewing the Regulatory Process

• Formal Mechanisms
• Fast Track
• Priority Review
• CMA Pilots 1 and 2
• Accelerated Approval

10
Fast Track

• Designed to facilitate the development and
  expedite the review of new drugs that are
  intended to treat serious or life-threatening
  conditions and that demonstrate the potential to
  address unmet medical needs.
• Incorporates an end of Phase I meeting
• Allows for more frequent communications with the
  FDA
• May allow for a rolling review of the BLA

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Priority Review

• For products that have the potential for
  providing significant preventative, diagnostic,
  or therapeutic advance as compared to existing
  treatments for serious or life-threatening
  conditions
• Complete action due 6 months after the date of
  submission

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Accelerated Approval

• Allows expedited marketing of new drugs or
  biologics intended to treat serious or
  life-threatening illnesses and that appear to
  provide meaningful therapeutic benefits compared
  with existing treatments.
• Approval based on a determination that the effect
  of a product on a surrogate endpoint is
  reasonably likely to predict its clinical benefit
  (21 CFR 314.510 601.41)
• Post-licensure confirmatory studies required

13
Continuous Marketing Application

• FDA is conducting 2 pilots to determine whether
  providing early review and additional feedback
  and advice to sponsors during drug development
  for selected products can further shorten drug
  development and review times
• Pilot 1 FDA has agreed to provide discipline
  review letters under PDUFA timelines for
  pre-submitted reviewable units of a BLA
• Applies only to Fast track designated products
• Pilot 2 frequent scientific feedback and
  interactions during drug development

14
Conclusions

• Despite ongoing budgetary challenges and
  increasing responsibilities, e.g.,
  counter-terrorism activities, influenza vaccine
  shortages, and other mandates, CBER has made
  significant progress in addressing all of the
  recommendations outlined in the NVAC Report on
  Vaccine Supply

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Conclusions

• CBER has met or exceeded all of its PDUFA goals
• CBER has increased the number of formal as well
  as informal meetings with industry to facilitate
  the development of new vaccines, and continued
  supply of currently licensed vaccines
• CBER has increased communications with its
  international regulatory counterparts through
  MOUs