FDA issued vaccine EUAs without facility inspections: GAO

Regulatory NewsRegulatory News | 01 November 2021 |  By 

Manufacturers of COVID-19 vaccines currently authorized for emergency use did not undergo facility inspections before their vaccines were authorized by the US Food and Drug Administration (FDA), said the General Accounting Office (GAO) in a new report. However, most facilities had been inspected at least once previously in past 10 years, and the agency relied on a variety of other information sources including record reviews and on-site reviews.
The examination of the US Food and Drug Administration’s oversight of the production of COVID-19 vaccines was part of a sweeping congressional report examining the federal response to the COVID-19 pandemic and released last week by GAO. The report meets some of the required reporting and oversight obligations included in 2020’s Coronavirus Aid, Relief, and Economic Security (CARES) Act.
The report includes an enclosure that gives an overview of FDA’s oversight of manufacturing quality for COVID-19 vaccines, including the three for which the agency has issued an emergency use authorization (EUA). In all, FDA had inspected 14 of the 18 vaccine manufacturing establishments for the three vaccines – made by Pfizer, Moderna, and Janssen – for a total of 90 inspections since October 2011. “For all but one of these 14 establishments, FDA’s most recent inspection was within the last 4 years,” according to the enclosure.
GAO found that one drug substance facility for each of the three vaccines had not been inspected; FDA had also not inspected one facility that manufactures the lipid nanoparticles that help stabilize the Pfizer mRNA drug substance.
By August 2021, FDA had completed visited three manufacturing establishments, for a total of three site visits and five investigations to gauge manufacturing quality. One facility that received a pre-EUA site visit had not been inspected for the 9 years preceding that visit. FDA also requested records for three establishments; the agency also received reports from other regulatory bodies for the seven manufacturing establishments that were located outside the US.
FDA since conducted six vaccine manufacturing establishments during the period from April through July 2021, after EUAs were issued but before approval of any biologics license application (BLA). The GAO report details the serious issues identified at the Emergent facility in Baltimore that Janssen and AstraZeneca had each contracted with, noting that the inspection “identified multiple serious deficiencies related to manufacturing quality control systems, building design, equipment, and personnel training.”
A corrective action plan from Emergent and subsequent cooperation with FDA meant that by July 2021, FDA no longer objected to the resumption of Janssen COVID-19 vaccines at the Baltimore Emergent plant.
FDA has relied on recent and previous inspections, as well as on-site reviews, in its ongoing appraisal of manufacturing quality for three vaccines not yet authorized or approved. AstraZeneca, Novavax and Sanofi/GSK vaccines are all receiving ongoing FDA review as part of the clinical trial process.
GAO also gathered information about FDA inspection of biologics manufacturing in general during the pandemic, finding that the total number of surveillance inspections dropped from 1,535 in 2019 to just 608 in 2020. Pre-approval or pre-license applications also fell by more than half, from 101 in 2019 to 46 in 2020.
“During the COVID-19 pandemic, FDA gave higher priority to establishments that manufactured products related to the COVID-19 response or products used to treat serious diseases or medical conditions for which there is no substitute,” wrote the GAO report authors. “Mission-critical inspections may include both domestic and foreign establishments.”
As with vaccine and drug quality oversight, FDA relied on records requests to fill part of the information gap when inspections were deemed infeasible or unsafe. The agency requested records from just 179 biologics establishments in 2019, but called for records from 601 such establishments in 2021.
For COVID-19 biologic treatments, FDA followed a similar path as for vaccines, relying on records, remote visits, and, when necessary, investigations and site visits to glean needed information about the quality of biologics for which EUAs or licensure was sought.
Additionally, the report notes that when rapid antigen tests for SARS-CoV-2 are purchased over the counter and used at home, results are not likely to be reported or tracked, so those test results are not included in trackers maintained by the US Centers for Disease Control and Prevention, and others. According to the report, FDA had issued a total of 36 EUAs for antigen tests, including 8 for tests that are authorized for at-home over-the-counter use.
“FDA does not have the authority to require individuals to report over-the-counter test results. However, FDA officials told us they worked with manufacturers during the emergency use authorization application process, as well as during town halls they hosted with manufacturers, to identify approaches that encourage and facilitate such reporting by individuals,” wrote report authors.
FDA was not named in any of the report’s 16 recommendations for action.
GAO report


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