21 CFR Part 601 and Vaccine Approval

21 CFR Part 601 and Accelerated Vaccine Approval: Five Things You Need to Know

21 CFR Part 601 Provides Basis for Accelerated Vaccine Approval

The recent bird flu outbreak in England has renewed public interest in the FDA’s pandemic influenza preparedness. The FDA, led by the Center for Biologics Evaluation and Research (CBER), is strengthening the country’s ability to meet a possible pandemic flu by developing regulatory pathways and processes that will speed up vaccine availability.

A pandemic flu occurs when a new influenza virus emerges for which people have little or no immunity, and for which there is no vaccine. The disease spreads easily from person to person, and can sweep across the country, or around world, in a short time.

More than 2,000 turkeys in a farm in Suffolk County, England, died early February from the outbreak of the H5N1 strain of avian flu. Thousands more were gassed by authorities to prevent the spread of the virus. The H5N1 virus has killed 167 people worldwide since 2003. Scientists fear that it would mutate into a form that could be easily transmitted between humans.

The FDA has released two guidance documents (one for seasonal flu and another for pandemic flu vaccines) providing manufacturers with information on developing and submitting clinical data for new vaccines. The documents describe: (a) the process for a speedy switch from currently licensed vaccines to a new pandemic vaccine by supplementing the existing license; and (b) pathways for both traditional and accelerated approval approaches for new vaccines.

Accelerated Approval

Accelerated approval allows for evaluation based on biological indicators. 21 CFR 601 is the basis for CBER’s authority to grant accelerated approval, a process that could shorten approval time to one to two years.

Here are a few things to note about accelerated approval.
1. When to Use Accelerated Approval. The regulation provides that accelerated approval may be used when:

  • A serious or life-threatening condition exists and there’s a lack of available alternative therapies (21 CFR 601.40).

  • There are surrogate endpoint studies showing that it’s reasonably likely to predict the clinical benefit of the therapy (21 CFR 601.41).

2. Approval with Restrictions. Under 21 CFR 601.42, the FDA may approve a biological product with restrictions to ensure safe use. The restrictions may include:

  • Distribution restricted to certain facilities/physicians with special training or experience.

  • Distribution conditioned on performance of specified medical procedures.

3. Further Studies. Approval under 21 CFR 601.41 will be subject to the requirement that the applicant study the biological product further. Post-marketing studies would usually be already underway. When required, such studies must be adequate and well-controlled, and should be carried out with due diligence.

4. Post-marketing Safety Reporting. Biological products approved under the “accelerated approval” program are subject to the post-marketing recordkeeping and safety reporting requirements applicable to all approved biological products.

5. Withdrawal Procedures. For biological products approved under this program, approval may be withdrawn for a number of reasons, such as:

  • Post-marketing clinical study fails to verify clinical benefit.

  • Applicant fails to perform the required post-marketing study with due diligence.

  • Use after marketing shows that post-marketing restrictions are inadequate.

  • Applicant fails to adhere to the post-marketing restrictions agreed upon.

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FDA Links

  • 21 CFR 601, Subpart E, Accelerated Approval of Biological Product

  • Expediting Development of Flu Vaccines

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    Draft Guidance (Licensure of Trivalent Inactivated Influenza Vaccines)

  • Draft Guidance (Licensure of Pandemic Influenza Vaccines)