Emergent BioSolutions’ Bayview Site Gets Form 483 Following FDA Inspection

FDA investigators observed multiple problems at Emergent BioSolutions’ beleaguered Bayview facility in an April 12 to April 20 inspection prompted by a manufacturing mix-up for Johnson & Johnson (J&J)’s and AstraZeneca (AZ)’s COVID-19 vaccines, making it unlikely that the plant will be authorized to produce J&J doses anytime soon.

At the same time, two high-ranking congressional Democrats have launched an investigation to determine if Emergent “leveraged its relationship” with a Trump administration official to obtain the federal COVID-19 contract for its Bayview facility, citing concerns over the vaccine material mix-up.

In an unusual move, the FDA released the Form 483 inspection report Wednesday, highlighting the high-profile status of the Bayview facility and the agency’s stated goal of being transparent during the pandemic. The document lists nine observations that were made by three investigators during the eight-day inspection, casting doubt on the facility earning Emergency Use Authorization (EUA) by the end of April that would have enabled it to contribute millions of monthly J&J vaccine doses for U.S. vaccination efforts.

Production was put on hold at the Bayview plant midway through the FDA’s recent inspection. The agency’s assessment of the facility, which is located in Baltimore, Md., was spurred by a widely publicized mistake at the plant in which a mix-up of materials for the AZ and J&J vaccines made 15 million J&J doses unusable (DID, April 20). The doses were intended for use in Europe. The incident led the U.S. government to intervene, ending production of AZ vaccine at the plant and putting J&J in control of the facility (DID, April 6).

The FDA’s 483 observations found the firm did not thoroughly investigate cross-contamination of a vaccine drug substance batch — presumably a reference to the AZ and J&J material mix-up, though the document has redactions that prevent confirmation. In its 483 observations, the agency noted a number of issues, including that the company’s investigation did not consider the operator who weighed and dispensed the raw materials for a media batch that was cited as the most likely cause of the cross-contamination. Another issue, the agency said, was that the company’s investigation did not thoroughly review personnel movements in and around the facility as a potential source of contamination, and the agency saw no assurance that other batches were not cross-contaminated.

The investigators’ observations also found issues with cleaning, sanitation and waste handling. It discovered multiple issues with handling of waste, including that workers did not decontaminate waste produced during manufacturing. Instead, they transported the waste through the warehouse prior to disposal and created a risk of contamination, the 483 said.

In another observation, workers were seen on camera carrying unsealed bags of special medical waste from a manufacturing area, with the bags touching containers of staged manufacturing materials, walls and fence barriers in a warehouse corridor. Workers were also observed throwing unsealed bags of special medical waste into the service elevator accessing a warehouse corridor.

Additionally, peeling paint and wall damage were observed in corridors surrounding manufacturing rooms, and residue, paint flecks, debris and a washer were observed on the floor of a room during the filling of a vaccine drug substance batch, among other issues.

Employee training was another issue identified after reviews of security camera footage, with the agency concluding that “the firm has failed to adequately train personnel involved in manufacturing operations, quality control sampling, weigh and dispense, and engineering operations to prevent cross-contamination.”

The FDA said that it is currently working with Emergent to address the observations outlined in the 483, and that it will not allow any vaccines to be released from the facility “until we feel confident that [the facility] meets our expectations for quality.”

Emergent acknowledged the Form 483 Wednesday, stating that the company would move quickly to fix the problems the FDA identified.

“While we are never satisfied to see shortcomings in our manufacturing facilities or process, they are correctable and we will take swift action to remedy them,” Emergent said.

J&J said that it will “exercise its oversight authority to ensure that all of FDA’s observations are addressed promptly and comprehensively” and “redouble its efforts as it continues to work toward securing EUA in the U.S. for drug substance manufactured at Emergent Bayview.”

This is not the first time that the Bayview plant has had issues with FDA inspections. In April 2020, an agency inspection observed insufficient employee training, unsecured records and a deficient method for preventing contaminations or mix-ups. Other deficiencies have been observed during inspections in previous years.

Meanwhile on Capitol Hill, Reps. Carolyn Maloney (D-N.C). and James Clyburn (D-S.C.), are looking into the $628 million contract the company received in June 2020 to set up its Bayview site for J&J and AZ vaccine manufacturing. The lawmakers claim that Robert Kadlec, a former Emergent consultant and assistant secretary for preparedness and response in the Trump administration, pushed for the contract “despite indications that Emergent did not have the ability to reliably fulfill [the contract]” and an alleged “long, documented history of inadequately trained staff and quality control issues” at the Bayview site.

The Democrats called on Emergent to produce by May 3 all contracts between the company and HHS between 2015 and now, as well as all inspection, audit and risk assessment documents related to manufacturing, quality and compliance at the Bayview facility from 2017 to the present, among other information, including documents regarding the mix-up incident.

The lawmakers also requested that Emergent CEO Robert Kramer and Executive Chairman Fuad El-Hibri testify before the House Select Subcommittee on the Coronavirus Crisis on May 19.

Read the full Form 483 here: www.fdanews.com/04-21-21-Emergent483.pdf. — James Miessler