The push for a vaccine for the COVID-19 pandemic may have no parallel in pharmaceutical history, and FDA commissioner Stephen Hahn vowed in a Senate hearing that the agency will rely on the agency’s traditional standards for scientific evidence in premarket reviews of those vaccines. Hahn made that statement shortly after the agency issued a guidance that includes a number of requirements regarding enrollment of those vaccine studies, but which also suggests some flexibility where on-site inspections are concerned.

Hahn was speaking at the June 30 hearing of the Senate Health, Education, Labor and Pensions (HELP) Committee, and said the agency is undergoing “a comprehensive, real-time review” to assess the efficacy of the agency’s actions in response to the pandemic. Hahn noted that among the agency’s actions for vaccine development is a guidance that includes requirements for data that are included in a vaccine biologics license application (BLA), along with mandates for clinical development and demographics for enrollment. Despite the intense pressure to move a vaccine out of trials and into routine use, Hahn said the FDA “will not cut corners” when it comes to the evidentiary standards for vaccine BLAs.

Guidance not a draft, but will be revised post-emergency

The COVID-specific guidance, which falls under an overarching entry at regulations.gov, said that its terms “will continue to apply” outside the context of the public health emergency, although any revisions will be made within 60 days of the termination of the emergency. Development can be accelerated on the basis of experience with “the same well-characterized platform technology,” the guidance said, while some aspects of manufacturing and controls may likewise be based on an existing vaccine platform. However, the FDA advised sponsors to consult with the agency on the data needed for the chemistry, manufacturing and controls section of a vaccine BLA.

In some circumstances, the FDA will allow validation of fill operations to be completed after product approval, assuming product quality is not compromised. Pre-licensing inspections have not been jettisoned as a result of the pandemic, but the agency said inspections can be managed with the help of a review of facility’s compliance history and a review of records, which may be used in lieu of on-site inspections. Patients at elevated risk of severe outcomes for COVID-19 may be excluded from early-phase studies, but pivotal trials must include racial and ethnic minorities, as well as elderly patients and those with co-morbidities. While the FDA is amenable to cluster randomization, the agency expressed a preference for randomized, controlled trials enrolled 1:1 to placebo. An existing vaccine for the SARS-CoV-2 virus may be used as a control treatment for subsequent candidate vaccines, the guidance said.

Alexander cites the politics of the mask

HELP Committee chairman Sen. Lamar Alexander (R-Tenn.) said Congress has been advised that members and witnesses at congressional hearings can speak into a microphone without a mask so long as they are separated by six feet. Otherwise, he wears a mask on the advice of the CDC, but Alexander also remarked that the venerable N95 mask “has become part of the political debate.” However, he said he has suggested to President Trump that the president wear a mask even at times when it isn’t necessary as a means of setting an example, but also as a way to shut down a distractive political debate. Alexander posted a June 28 press release making much the same case.

Anthony Fauci, director of the National Institute of Allergy and Infectious Diseases (NIAID), said the NIH-NIAID strategic plan for vaccines is largely focused on the components of the virus that trigger an immune response. However, he said there is an interest in a harmonization of the trials of the various vaccines to ensure similar outcomes are measured.

There is still no guarantee a vaccine will be available by year’s end, Fauci said, but he added, “hopefully there will be doses available by the beginning of next year.” He noted that a new swine flu based on the H1N1 virus has emerged in China, which has acquired nucleic acid proteins that were not present in the version of the virus that emerged in 2009. The authors of the journal article highlighting this pathogen describe it as bearing “all the essential hallmarks of a candidate pandemic virus.” Fauci said this virus does not present an immediate threat to the U.S., but said the situation should be tracked closely.

Sen. Rand Paul (R-Ky.) expressed some skepticism about expert opinion on the virus, pointing out that there are extensive data sets from a number of nations that indicate that children rarely transmit the SARS-CoV-2 virus. Paul argued that some experts have made recommendations on the basis of poor bodies of data, and pressed the urgency of reopening schools, a step that is critical to allowing parents to return to work.

Fauci said he agreed with Paul about the practice of offering opinions without the backing of solid data, but noted that “I feel strongly we have to do whatever we can to get the children back to school.” He stated that there are times when he is quoted in the media of having said something he never said, but added that he will continue to advise policymakers and the public on conclusions that can be reasonably drawn from the available data.

Robert Redfield, director of the CDC, made note of the fact that 29 U.S. states and territories have witnessed a significant jump in both hospitalizations and fatalities in recent weeks. He said racial and ethnic populations are disproportionately affected by the COVID-19 pandemic, adding that it is important to observe recommended mitigations. Redfield added that he was specifically addressing “the younger members of our society” with regard to mitigations.

Federal government IT seen as deficient

Both Redfield and Brett Giroir, assistant secretary for health at the Department of Health and Human Services, said their wish lists for future pandemics included a beefed-up federal information technology infrastructure. Redfield said he noticed shortly after taking the director’s job that the IT build at CDC was deficient, and Giroir said a more reliable data stream is crucial for a number of considerations, including supply chain management. FDA’s Hahn added that a better data infrastructure would allow the FDA and clinicians to better respond to emerging information about treatment efficacy during a pandemic, an especially critical consideration for extremely contagious pathogens.

“We absolutely need redundancy in the supply chain,” Hahn said, adding that domestic manufacturing of therapies and diagnostics must be resuscitated.

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