23/24 September 2021
It has recently been increasingly reported in the international press that there was a mix-up in the manufacturing of the Covid-19 vaccine by Johnson & Johnson (J&J). At the site of the contract manufacturer Emergent Biosolutions in Maryland, USA, where the AstraZeneca vaccine was also manufactured, workers had accidentally mixed up ingredients of the two vaccines. This affected 15 million J&J vaccine units.
The publication of the so-called Form FDA 483 report by the US Food and Drug Administration (FDA) has now revealed more details about the processes on site. The inspection which led to the 483 already took place in April 2020. In the meantime, this 483 report is no longer available on the FDA website, but there is a current report from April of this year, which goes into more detail about cross-contamination. Various deficiencies are listed here on a total of 12 pages.
One of the general failures was a lack of data integrity. Electronically generated data was not sufficiently protected from being subsequently changed or even deleted. This affected several systems, such as the data acquisition software, the analytical scales or the Windows operating system. There was no subsequent control through an audit trail review.
A second observation was made regarding compliance. Sample identification numbers were inconsistent and in some cases sample identification numbers were changed days later without giving reasons. Necessary investigations regarding the deviations and changes did not take place.
Test methods were also deviated from or changed without justification. If there were "invalid events", the same analyst often examined them. The SOP allowed for "verbal approval" to proceed with a retest. And so a retest was possible without an independent investigation and final evaluation of the invalid event.
Contamination or mix-ups were not adequately prevented. Rejected materials or batches were inadequately stored or labelled.
There were further FDA inspections in September 2020 and February 2021, but the results have not yet been published. And so now the current mix-up occurred.
According to a report in the New York Times, as a consequence, the Biden administration ordered the site to produce only J&J vaccine - directly under the responsibility of J&J. The quite extraordinary step by the Department of Health and Human Services came only a few days after it became known that there were quality problems at Emergent BioSolutions. Taking out the AstraZeneca vaccine means that in future only J&J vaccine will be produced at the site until further notice in order to avoid further mix-ups.
So far, none of the J&J vaccine batches produced at Emergent have been released. Investigations are ongoing to determine whether other batches of the vaccine have been contaminated. Also, the site itself has not yet received final authorisation from the FDA to manufacture the vaccine.
FDA Acting Commissioner Dr Janet Woodcock said in a statement that the agency "takes its responsibility for helping to ensure the quality of manufacturing of vaccines and other medical products for use during this pandemic very seriously."
But she also made it clear that the ultimate responsibility lies with J&J: "It is important to note that even when companies use contract manufacturing organizations, it is ultimately the responsibility of the company that holds the emergency use authorization to ensure that the quality standards of the FDA are met."
In a statement from J&J, the company highlights what happened as "an example of the rigorous quality control applied to each batch of drug substance. The issue was identified and addressed with Emergent and shared with the United States Food & Drug Administration (FDA)."
In the meantime, the FDA has ordered Emergent BioSolutions to temporarily halt production of Covid 19 vaccines materials, according to the press. First, US regulators are to investigate the Baltimore plant and the problems there in more detail. The order came as part of another inspection that began on 12 April 2021. Only four days later, the company was asked to stop production.