FDA Q&A: The Approval Process for Vaccines and Trumenba With Rachael Conklin: Communications Officer

Last month, the FDA approved Trumenba, a vaccine for meningitis B. Meanwhile, the vaccine that was administered to Princeton students last year, Bexsero, continues to be under review. Below, PPHR discusses the vaccine approval process with FDA Consumer Safety Officer Rachael Conklin.

PPHR: What considerations does the FDA have when approving a new vaccine?

Conklin: The main considerations are the same for approving a vaccine as for approving any other drug product: safety and efficacy. The Center for Biologics Evaluation and Research is the part of the FDA responsible for regulating vaccines. Vaccine clinical pathways follow the same pathways as other drugs listed in Section 351 of the Public Health Service Act. A sponsor who wants to begin a clinical trial in humans would need to submit an Investigational New Drug Application (IND) to the FDA. This IND describes the vaccine, the methods of the manufacturer, the quality control process for release, and any information on the vaccine’s safety and ability to elicit a protective immune response in animal testing. The FDA would review this IND and either give the sponsor permission to proceed with the clinical trials or put the IND on hold if they have any concerns about the data taken from the animal or other preclinical studies.

PPHR: What is the process and how long does it usually take?

Conklin: Vaccine clinical trials are typically done in three phases. Initial preclinical studies are referred to as Phase 1. Phase 2 is concerned with safety and immune responses in a closely monitored group of subjects to make sure that the appropriate responses are seen in humans as well. Phase 3 deals with thousands of human subjects, which will provide the critical documentation for the effectiveness and safety of the vaccine. During this phase, the FDA looks for the possibility of other adverse effects previously undiscovered in Phase 2. If it passes through all three phases successfully, the sponsor or manufacturer will submit a Biological License Application, which the FDA will review for consideration for approval. The applicant must give the FDA review team the safety and efficacy data to recommend the approval of the vaccine. There will also be an inspection of the sponsor’s manufacturing facility and process. After, the findings will be presented to the FDA’s Vaccines and Related Biological Products Advisory Committee, in which experts will decide whether or not they should make a recommendation.

The timeline of this approval process depends on the drug or vaccine in question. The FDA may hold the process and ask for more safety or efficacy data at any time. However, there are a number of expedited programs that can be used to speed up the approval process if the drug or vaccine will treat life-threatening illnesses. For instance, the vaccine Trumenba was given Breakthrough Therapy Status.

The criteria for Breakthrough Therapy Status designation includes whether or not the product is intended to be used alone or in combination with one or more drugs to treat serious or life threatening diseases and if preliminary evidence indicates that the product may demonstrate substantial improvement in a clinically significant study endpoint or other available therapies. The sponsor of the FDA may discern what the endpoint of a study may be that would make the vaccine or drug worthy the status. This status gives sponsors more specific guidelines during the IND stage and organizational help from senior officers in the FDA. The sponsor may also have a rolling deadline for the Biological License Application, in which they can submit parts of the application at a time. This allows for more feedback from the FDA.

The FDA also utilized the Accelerated Approval Regulatory Pathway for Trumenba. The vaccine received this designation because of its effectiveness in killing four types of antibodies representative of the serogroup B strains of meningitis. As part of this process, the manufacturer will continue to conduct further studies to verify Trumenba’s effectiveness against diverse strains of serogroup B meningitis.

PPHR: What types of data does the FDA look at in order to approve new drugs or vaccines?

Conklin:This is dependent on the drug or vaccine. The FDA works with the sponsor to suggest the data needed from the IND stage as well as the clinical trial stages.

For Trumenba, because the serogroup B disease is uncommon in the US, the effectiveness of the vaccine was measured by the immune responses of the antibodies in vaccine recipients.
Safety data on potential side effects was collected from 4500 individuals who received the vaccine. The most commonly reported side effects were pain and swelling at the injection site, headache, diarrhea, muscle pain, joint pain, fatigue, and chills.

Other vaccines may use an endpoint other than immune response. This endpoint depends largely on the nature of a vaccine or drug. For instance, a cancer drug efficacy endpoint may be the shrinking of a tumor. The FDA also takes into account data from all the other components of the vaccine, like the manufacturing process in later stages.

PPHR: Was Trumenba compared with any other existing vaccines in efficacy studies? If so, did the Trumenba perform better?

Conklin: The FDA does not compare products between one another for the basis of approval. Vaccines go through separate processes for approval.

PPHR: Are studies still being performed on Trumenba, given that it had only taken six months to approve it?

Conklin: Part of the approval letter for Trumenba states postmarketing requirements for the vaccine. In this case, more tests on the vaccine need to be conducted to confirm its effectiveness against diverse meningococcal group B strains in the age groups 10-19 and 18-26 years old. If these studies are not completed before an approved timeline, the FDA may withdraw or modify its approval.

PPHR: Why is Bexsero approved in Canada, Europe, and Australia, but not in the U.S.?

Conklin: The FDA can only approve products whose applications were submitted from a pharmaceutical sponsor or manufacturer. The proposal for Bexsero to acquire a Biological License Application in the U.S. was only submitted in June 2014. The FDA does not comment on the status of vaccine or drugs pending approval.

PPHR: Will the Bexsero vaccine that Princeton is currently giving out be phased out for the FDA-approved Trumenba?

Conklin: The Bexsero IND was approved for expanded access use of the vaccine, which means it may be used when there is no comparable or satisfactory alternative therapy. Therefore, Bexsero will continue to be given to students who have already received the first dose or who need to be immunized before Trumenba is made available. The FDA understands that the University plans to vaccinate freshmen until November, which is acceptable as Trumenba’s prescribing information explains that the serogroup B meningococcal vaccines should not be interchanged.

PPHR: Was Trumenba a viable candidate for vaccination a year ago?

Conklin: The United States was the first country to approve Trumenba, so it was not a viable candidate for the expanded access IND to combat the meningitis outbreak. In order to be a viable candidate for unapproved use, a vaccine must have no other FDA-approved alternative and show data for efficacy and safety studies.