How did 75M J&J vaccines get ruined? FDA details the manufacturing woes at Emergent's beleaguered site

At long last, several million doses of Johnson & Johnson's COVID-19 vaccine made at CDMO Emergent BioSolutions' troubled Baltimore production facility have been cleared for use. But many more are now bound for the graveyard, and the feds are going public with the reasons behind the ruined doses.

Emergent has been in hot water ever since a manufacturing error at its Baltimore plant forced the CDMO to discard up to 15 million Johnson & Johnson COVID-19 vaccine doses this spring. Following weeks of inspection, the FDA last week cleared about 10 million doses to ship out to the U.S. and other countries. At the same time, the feds also instructed the companies to toss about 60 million more doses.

That's a total of about 75 million discarded doses from the plant, and about 10 million approved for shipment.

In a Friday memo, FDA biologics and vaccines official Peter Marks, M.D., Ph.D., explained the agency's rationale and provided an update on the production work.

Back in early March, out-of-specification testing results flagged an initial drug substance batch dubbed GMP 8, Marks wrote. That eventually led the companies to discard the initial 15 million doses.

After the out-of-spec test, J&J performed more testing and found contamination with AstraZeneca's vaccine—also being made at Emergent's Baltimore plant at that time. The company reported its findings to the FDA on March 26, the memo said.

RELATED: Zero Johnson & Johnson COVID-19 vaccine doses set to ship next week as production holdup lingers

The contamination scare sent FDA inspectors back to Emergent's plant in April, where they found that the production and waste flow issues affecting the GMP 8 batch also extended to four other drug substance batches numbered 5, 6, 7 and 9. Specifically, Emergent was grappling with significant increases in production "coupled with a lack of segregation of media preparation activities, waste flow, and personnel handling waste," Marks wrote.

Now, after investigating, the FDA has declared that the four additional batches weren't made in accordance with its manufacturing standards and has asked that they be discarded. It said that "the safety and effectiveness of these batches cannot be assured," and noted that J&J's emergency use authorization would not be updated to include them. 

As for the two batches the FDA cleared—GMP 2 and GMP 4—Emergent's Baltimore plant still wasn't fully compliant during their production, Marks said. But the agency has confirmed they're suitable for release based on facility records and results from in-process and release testing. Put simply, "GMP2 and GMP4 were produced prior to the overloading of the facility’s capacities and the transit of waste in the area that led to the cross-contamination," Marks wrote.

RELATED: Emergent CEO takes 'full responsibility' for COVID-19 vaccine manufacturing flubs, but offers little in the way of answers

Emergent started its COVID-19 vaccine production last year work by scaling up the AstraZeneca drug substance process in August. By September, an FDA inspection cited the plant for crowded manufacturing space, poor quality assurance support and several laboratory controls shortfalls, the memo said. The FDA also flagged the need to improve material and equipment flows through the facility. 

A few months later, in November, Emergent had incorporated the J&J vaccine production work into its operations. The J&J production scale-up caused the CDMO to generate much more waste, which Emergent wasn't set up to handle, the FDA said. The agency also flagged concerns over personnel changes, record keeping, and consistency during a February 2021 inspection.

After months of work to improve the situation, Emergent is "pleased that these initial doses of the Johnson & Johnson COVID-19 vaccine will be available to protect millions of people from this deadly disease,” CEO Bob Kramer said in a statement last week. The company is working on issues in Baltimore and plans to keep making drug substances for J&J's shot once the problems have been put to bed, the company added.

Still, the damage has already been done in places like South Africa, which is reportedly discarding 2 million Johnson & Johnson doses. Meanwhile, Canada has rejected 300,000 Emergent-made doses and said it wouldn't accept any more J&J shots made at the CDMO's Baltimore plant until it can inspect the facility itself.

For its part, Germany was in line to receive some 10.1 million Johnson & Johnson doses in the second quarter of 2021. The country is now pressing J&J to deliver 6.5 million doses in July to make up for an expected shortfall this month.