In addition to safety questions about its COVID-19 vaccine, Johnson & Johnson (J&J) is facing manufacturing challenges as a key partner, Emergent Biosolutions Inc., has yet to get FDA approval to manufacture or distribute the vaccine or its components in the U.S.

That approval could be awhile in coming. On April 21, a day after completing its onsite inspection of Emergent’s Bayview plant in Baltimore, Md., the FDA released Form 483 from its inspection, revealing nine observations related to cross-contamination issues, lack of employee training and poorly designed and maintained facilities.

During the nine-day inspection, FDA investigators noted peeling paint and residue on floors and walls, repairs being made in the manufacturing area while drug materials were present and employees throwing unsealed bags of “special medical waste” into a service elevator in the manufacturing area. Other examples cited included employees carrying bags of unsealed waste across the manufacturing area, bumping into walls and containers of staged manufacturing materials, and facilities poorly designed for proper operation, maintenance and cleaning.

At the FDA’s request, Emergent agreed to pause production of vaccines while it works to resolve the quality issues. Vaccines already manufactured at the plant “will undergo additional testing and will be thoroughly evaluated to ensure their quality before any potential distribution,” according to the FDA.

While that’s being done, J&J said it is establishing a global vaccine supply network to meet the commitments it made for its COVID-19 vaccine. In addition to J&J’s internal manufacturing site in Leiden, Netherlands, the network will include 10 manufacturing sites across the globe. “We are working around the clock to develop and broadly activate our manufacturing capabilities to supply our COVID-19 vaccine worldwide,” the New Brunswick, N.J., company said.

As for the inspection report, J&J said it would exercise its oversight authority to ensure Emergent addresses all the FDA’s observations promptly and comprehensively. It added that it would “redouble its efforts” in continuing to work toward securing emergency use authorization in the U.S. for the drug substance manufactured at the Bayview facility as quickly as possible.

More than a week before the inspection began, J&J had announced it was assuming full responsibility for the manufacturing of the drug substance for its COVID-19 vaccine at the Emergent plant, saying it would add “dedicated leaders for operations and quality and significantly increas[e] the number of manufacturing, quality and technical operations personnel to work with the company specialists already at Emergent.”

In the 483 report, FDA investigators referenced a “cleanout” that was conducted during the inspection; however, labs and other areas were still too crowded to alleviate the potential for cross-contamination.

Concerns about the Bayview plant were raised when Emergent stopped drug substance production at the facility after identifying a single 15 million-dose batch of the drug substance for J&J’s vaccine that had been contaminated with ingredients from Astrazeneca plc’s COVID-19 vaccine. The batch was discarded, and J&J chalked the misstep up to human error.

Besides the J&J doses, the plant had to destroy millions of doses of Astrazeneca’s vaccine manufactured between October 2020 and January 2021 due to suspected contamination, U.S. Reps. Carolyn Maloney (D-N.Y.), chair of the House Committee on Oversight and Reform, and James Clyburn (D-S.C.), chair of the Select Subcommittee on the Coronavirus Crisis, wrote in an April 19 letter to Emergent officials.

The FDA chided Emergent in the 483 for not adequately investigating the cross-contamination. Agency investigators noted several employee actions and storage conditions that may have caused or contributed to the problem. For instance, although the surface viability of the virus used in the vaccine substances isn’t known, Emergent did nothing more than routine cleaning between different batches, according to the 483, which added that there’s “no assurance that other batches have not been subject to cross-contamination.”

According to the Maloney-Clyburn letter, another 62 million vaccine doses are in jeopardy until it can be determined whether they were contaminated.

Congressional investigation

Getting the Bayview facility up to FDA standards is just one challenge facing Emergent. Maloney and Clyburn’s committees have launched an investigation into whether Emergent leveraged its relationship with Robert Kadlec, who had worked as a consultant for the company before serving as Health and Human Services (HHS) assistant secretary for preparedness and response under President Donald Trump, to profit from federal contracts and whether its actions impeded the U.S. response to the COVID-19 crisis.

Some of the actions the lawmakers referenced preceded the Trump administration. For instance, Emergent received a $163 million contract from HHS in 2012 to retrofit and expand its Baltimore manufacturing plant to increase its ability to rapidly manufacture vaccines in the event of an infectious disease outbreak or biological attack. According to Maloney and Clyburn, the contract, awarded under the Obama administration, required Emergent to show it could produce 50 million doses of a pandemic influenza vaccine within four months and, through a partnership with a company developing a flu vaccine, to gain FDA manufacturing approval by June 2020.

Despite Emergent’s failure to meet that deadline and two FDA inspections last year of the Baltimore plant that revealed the facility didn’t have the necessary trained personnel to produce a coronavirus vaccine, the company received $628 million in government funding last June to manufacture COVID-19 vaccines, according to the lawmakers’ letter. “We are concerned by the costs to taxpayers and the potential impact on our nation’s vaccination efforts caused by Emergent’s failed attempts to manufacture these vaccines,” Maloney and Clyburn added.

Their investigation isn’t limited to Emergent’s COVID-19 vaccine manufacturing problems. Maloney and Clyburn also are looking at Emergent’s contract to provide an anthrax vaccine to the Strategic National Stockpile (SNS). Then known as Bioport, Emergent paid the state of Michigan $25 million in 1998 for the license to Biothrax, the only FDA-licensed vaccine to prevent anthrax infections. At the time, the price of a dose of the vaccine averaged about $3.35. By 2010, Emergent had raised the price it charges the government to about $28 per dose. Today, the government price is more than $30 per dose, with average wholesale prices reaching $90 per dose.

Although the anthrax threat has been low since 2012, Kadlec’s office awarded Emergent $3 billion in long-term contracts for vaccines against anthrax and other bioterrorism threats in the months before the COVID-19 pandemic hit last year. During Kadlec’s tenure at HHS, “Emergent’s anthrax vaccine contracts put an enormous strain on the budget for the SNS, contributing to critical supply shortages that impacted the nation’s ability to respond to other threats,” according to the letter.

Maloney and Clyburn claimed that the $370 million the government spent last year on Emergent’s anthrax vaccine is directly related to the SNS shortages of basic medical supplies needed during the pandemic.