Following a severe season of respiratory syncytial virus, or RSV, in the U.S., multiple companies have reported that they have promising vaccine candidates for various patient populations in the late-stage clinical trial pipeline. The FDA could approve some of them as early as this year, for what is estimated to be a market worth more than $10 billion.
But just because the agency approves these vaccines doesn’t mean that many people will immediately have access to them. The process of gaining commercial health plan coverage for a vaccine is complex, and often results in lengthy delays before payers can cover an FDA-approved agent. Read on for an in-depth look at the coverage process in this post, the first in a series on vaccines.
Completing Research and Phases I, II, and III
The road to FDA approval ensures that vaccines are safe and effective. Scientists first undergo laboratory research on a vaccine candidate, a step that may include testing on animals. Then the vaccine goes into the preclinical phase, when additional testing is performed, including testing in animals. A researcher or company then submits an Investigational New Drug application to the FDA that includes information on the candidate, such as preclinical testing results and the technology used to manufacture the product.
After its assessment is complete, the FDA can grant the company the ability to move the candidate into clinical development, which usually consists of three phases that are often sequential but may overlap. Phase I focuses on the safety of the product, which is tested on 20 to 100 healthy volunteers.
Once no safety concerns are found in that initial step, the product moves to Phase II, which includes randomized-controlled studies of various doses on hundreds of people who have different health statuses and represent different demographics. These studies assess immune response and collect additional safety information. In Phase III, thousands of people will receive the vaccine, and these studies provide effectiveness data and further safety information.
Verifying Manufacturing and Labeling
During the clinical trials, the FDA also is evaluating information around the manufacturing process, including the facility where vaccines will be produced. Once a consistent manufacturing process has been developed and the clinical trials are complete, companies can submit a Biologics License Application (BLA) to the FDA that seeks approval to market and distribute the candidate. An FDA scientific team featuring experts in various areas evaluates the submitted information. The agency also may seek input from a team of outside experts known as the Vaccines and Related Biological Products Advisory Board.
Once the FDA has assessed all this information and determined that prescribing information/labeling in the BLA supports the approved indication, dosage and administration, it approves the application. Sometimes the agency may require the manufacturer to conduct post-marketing studies. Various surveillance systems monitor the vaccine in real-world use to identify any unusual side effects.
Waiting for Confirmation of ACIP Recommendations
Even after the FDA approves a BLA, however, additional steps are required for many health plans to cover a vaccine.
The Advisory Council on Immunization Practices (ACIP) is a federal advisory committee consisting of medical and public health experts that develops recommendations on vaccine use in the U.S. for both children and adults. Deliberations by the group — which the U.S. Surgeon General established in 1964 — “include consideration of disease epidemiology and burden of disease, vaccine safety, vaccine efficacy and effectiveness, the quality of evidence reviewed, economic analyses, and implementation issues.”
In situations in which multiple manufacturers have created a vaccine for the same disease, ACIP typically does not recommend one manufacturer’s vaccine over another, but that’s not always the case. For example, the group recommended the shingles vaccine Shingrix over Zostavax.
ACIP’s recommendations are reviewed by the director of the Centers for Disease Control and Prevention (CDC). Once the director has approved those recommendations, they are published in the CDC’s Morbidity and Mortality Weekly Report (MMWR) and result in the official immunization schedules for adults and children in the U.S.
Individual and employer-sponsored private health plans subject to the Affordable Care Act’s preventive services coverage standards must provide coverage for individuals to receive vaccines that ACIP recommends without cost sharing. Within one year of the CDC’s adoption of ACIP’s recommendations, plans must update their coverage once a new plan year begins.
But that could be a bit of a wait. ACIP typically holds only three meetings each year, with meetings in February, June and October for the next three years. So if a manufacturer has a vaccine approved in October, and it is not reviewed until the February meeting, then final approval and publication wouldn’t occur until May. However, if the vaccine is not reviewed in February and must wait until June, then final approval and publication won’t happen until September — almost a full year after FDA approval.
Like any drug, vaccines have both benefits and risks, and no vaccine is completely safe and effective in 100% of people. However, the complex process of bringing a vaccine to market should assure the public that vaccines are safe and effective in the general population.