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COVID-19 Vaccines: Can US FDA Complete Assessment In Less Than Six Weeks?

COVID-19 Vaccines: Can US FDA Complete Assessment In Less Than Six Weeks?

Source : 'The Pink Sheet'

A 2020 emergency use authorization for a coronavirus vaccine still remains possible with interim data now available, but with less than two months left in the year, the pressure on US Food and Drug Administration staff to meet the expectation is growing.

Moderna, Inc. became the second vaccine sponsor to report interim results with its 16 November announcement that the independent data safety monitoring board determined the Phase III trial of its mRNA product showed the product with a 94.5% efficacy rate. The result was hailed by US government officials and others as another extremely positive result that bodes well for approval. 

Moderna, like competitor Pfizer Inc. and partner BioNTech SE, plans to file for an EUA in the coming weeks, and Anthony Fauci, director of the National Institutes of Health’s National Institute of Allergy and Infectious Diseases, said an EUA approval is projected in time for vaccine doses to be available by the end of the year.

Pfizer reported on 9 November an interim analysis from the Phase III trial of its mRNA vaccine candidate showed a 90% efficacy rate. ()

Such a timeline is feasible, said Norman Baylor, president and CEO of Biologics Consulting and a former director of the FDA Center for Biologics Evaluation and Research’s Office of Vaccines Research and Review, “albeit, it will be tight.”

Washington Analysis Executive VP and health care analyst Ira Loss also said the end-of-the-year approval time frame is possible, although it depends on when the applications are submitted.

“This is fast-moving stuff,” he said. “I have to take them at their word. I think they are all about getting this done as quick as possible.”

The FDA’s fastest full drug approval was Merck & Co., Inc.’s antiretroviral Crixivan (indinavir), which needed only 42 days (six weeks) from application submission to approval in 1996. GlaxoSmithKline plc’s Fluarix (influenza vaccine) also was among the leaders, requiring only 99 days (14 weeks) from submission to approval in 2005. ()

CBER Director Peter Marks has said that depending on the amount of data made available before the EUA application arrives, an assessment could take “weeks” to grant, as opposed to a BLA, which would take months to approve. ()

Unfortunately for the FDA, there are less than six weeks left before the end of 2020 to complete the necessary work. And that time is further squeezed given the Thanksgiving, Christmas and other holidays will arrive during that time.

The FDA also has pledged to hold advisory committee meetings for each vaccine candidate before making a decision. If both applications arrive about the same time, a multi-day Vaccines and Related Biological Products Advisory Committee meeting could be scheduled to streamline the process and allow for multiple approvals in short order.

Advisory committee meetings cannot be scheduled overnight. They require at least a 15-calendar-day notice, according to the FDA website, adding to the time crunch.

A substantial amount of work also must be done by both the FDA and the sponsors to prepare the vaccine EUA request. FDA guidance indicates that the sponsor should submit briefing materials for the advisory committee along with the EUA request. ()

VRBPAC member Paul Offit, a pediatrics professor in the Children’s Hospital of Philadelphia Division of Infectious Diseases, said that he has not heard any potential meeting dates yet.

The VRBPAC review could be a challenging one for sponsors and the FDA. When the committee met on 22 October to discuss coronavirus vaccine development and approval issues in general, panel members raised concerns about some of the agency’s stated efficacy and safety standards for the product ().

The committee also agreed that placebo controls should remain in place for ongoing clinical trials even after a vaccine receives an EUA in order to support full licensure, an issue that could create tension with sponsors. ()

Before the sponsors can seek their EUAs, they need a median of two months of safety data after patients have received their second dose. Moderna’s smaller trial could be an advantage here, but Pfizer had been enrolling faster.  

Moderna definitely seems to have an advantage when it comes to distribution requirements, In a separate release on 16 November, Moderna said that it expects “mRNA-1273 to be distributed using widely available vaccine delivery and storage infrastructure.” Pfizer’s product is expected to need ultracold storage processes.  

In contrast, Moderna says its vaccine should be handle shipping and long-term storage conditions at standard freezer temperatures (-20°C, or -4°F) for six months, and it is “now expected to remain stable at standard refrigerator temperatures of 2° to 8°C (36° to 46°F) for 30 days, up from previous estimate of 7 days.” Also, no dilution will be required prior to vaccination.

Combined with the higher efficacy, the easier logistics could make Moderna’s vaccine more appealing than Pfizer’s, but the acute demand suggests that each sponsor will be able to sell as much as it can make for the foreseeable future.   

In many respects, the speed of FDA review matters less than the speed of vaccine production at this point. And before distribution can begin, the Centers for Disease Control and Prevention’s Advisory Committee on Immunization Practices must determine who should receive the vaccine and prioritize the groups that should receive it while supplies are limited. ()

The ACIP decision will not be made until after a vaccine is approved or receives an EUA. ()

Moderna has said that about 20 million doses of its vaccine will be manufactured by the end of 2020 and that it will manufacture 500 million to 1 billion doses globally in 2021. The company received funding from the US government’s Operation Warp Speed (OWS) to produce doses in order to ensure distribution could begin as soon as possible.

Pfizer has said it expects to produce globally up to 50 million vaccine doses in 2020 and up to 1.3 billion doses in 2021. OWS has contracted with Pfizer to purchase its vaccine once it is available, but did not provide development funding for the product. ()

Moderna and Pfizer also are beginning work testing their vaccine candidates in children. ()

Johnson & Johnson and AstraZeneca PLC also have vaccine candidates in Phase III trials that could be on track for an EUA in early 2021, assuming positive results. ()

By Derrick Gingery