COVID-19 Vaccines - Inspections under Emergency Approvals in the US

The approach to the licensing of COVID-19 vaccines varied between the respective national authorities. While in the European Union a "rolling review" and conditional approval as the means of choice accelerated the approval of new vaccines, other countries, e.g. the US, chose the path of emergency approval. Rolling review is not an emergency approval, but works with prioritisation and accelerated procedures. Normally, a company submits its marketing authorisation application only when the complete marketing authorisation dossier is available, all studies are completed, the manufacturing process is on a firm foundation and the product is ready for approval. In the case of COVID vaccines, there is a so-called "rolling review". The companies can therefore, before they apply for the actual approval - submit in batches what is already ready and the authority has already examined these parts, evaluated them and identified any deficiencies before the next data package from the company comes in. This "parallel work" saves a great deal of time. These submissions were additionally prioritised in terms of time as well, so they were allowed to "jump the queue" everywhere. A conditional approval is regulated by law in the EU and means that data is still outstanding, the submission of which is mandatory, otherwise the approval expires. However, a thorough expert review of quality, safety and efficacy must already be possible for the initial approval, and this is carried out within the same framework as otherwise. The COVID vaccines are also subject to special monitoring - instead of every six months as is usually the case with new products, the companies must submit updated safety reports here every month. The clinical approval studies must be continued for another two years.

The conditional approval is not the same as a so-called "Emergency Use Authorisation", as was granted for the COVID-19 vaccines in the US and UK, for example. In the US, the FDA had chosen the path of emergency approval. For this purpose, a specially valid guideline "Emergency Use Authorisation for Vaccines to Prevent COVID-19" was created in order to guarantee quality and safety to the greatest possible extent. The FDA also commented in detail on this procedure for the first emergency authorisation in December 2020 (see "FDA Takes Key Action in Fight Against COVID-19 By Issuing Emergency Use Authorisation for First COVID-19 Vaccine").

GAO Report

However, such measures and the associated procedures are also subject to additional review and monitoring. In the US, one such institution is the GAO, the Government Accountability Office. This is the General Accounting Office, which as a non-partisan investigative body and which is subordinate to the United States Congress. In its reports, the GAO also published data from the FDA on the "Oversight of COVID-19 Vaccine Manufacturing Quality", which provide information on the extent to which the usual inspection intervals were waived in the context of emergency approvals, data on the manufacturing sites were already available beforehand and at which points inspections were carried out. For example, since October 2011, the FDA has had data from a total of 90 inspections for 14 of the 18 manufacturing sites for the three vaccines - produced by Pfizer, Moderna and Janssen. "For all but one of these 14 facilities, the last FDA inspection was within the last four years," the GAO report's appendices states. But the GAO also found that for each of the three vaccines, one drug manufacturing facility had not been inspected, as had a facility that makes the lipid nanoparticles that help stabilise Pfizer's mRNA drug. However, the inspections carried out in 2020 and 2021 also revealed deficiencies, for example at a manufacturing facility in Baltimore that produced vaccines for AstraZeneca and Janssen. According to the GAO report, "several serious deficiencies were found there related to manufacturing quality control systems, building design, equipment, and personnel training."

The GAO also provides information on the general frequency of inspections of biological pharmaceutical plants. The relevant section " FDA Inspections of Biologic Manufacturing during the COVID-19 Pandemic" shows that the total number of surveillance inspections decreased from 1,535 in 2019 to only 608 in 2020. The number of applications for prior authorisation or pre-licensing also fell by more than half, from 101 in 2019 to 46 in 2020.

More details can be found directly on the GAO website.