Bristol Myers hit with warning letter at AZ fill/finish plant

The US FDA highlighted contamination issues at a facility that produces cancer drug Abraxane but has been earmarked by Bristol Myers Squibb to become a biologics drug product plant.

The US Food and Drug Administration (FDA) inspected the facility in Phoenix, Arizona from March 28 to April 6, 2022 and issued a warning letter on October 31.

The violations noted in the letter included failures to sufficiently investigate contamination issues and to effectively implement corrective actions and preventive actions (CAPA).

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Specifically, “multiple media fill failures occurred between April and October 2021, when simulating aseptic processing operations on the filling line used for your drug product Abraxane,” the Agency wrote.

In one example, the FDA noted “ten different microbes” identified from samples of contaminated units “including sporeforming, vegetative, gram-negative, and gram-positive microbes” taken during a media fill.

“Your investigation attributed the root cause to (b)(4) in the filling manifold that included a damaged (b)(4) that was contaminated during (b)(4) equipment cleaning step. The investigation indicated that the valve harbored such excessive bioburden that it apparently enabled numerous bacteria to survive the subsequent filling equipment sterilization cycle, and the contaminated valve then caused the extensive contamination of units during the media fill.”

Abraxane is an injectable formulation of paclitaxel used to treat several cancers, including breast, lung, and pancreatic cancer. The mitotic inhibitor was developed by by VivoRx which became Abraxis BioScience, to whom the FDA addressed the letter.

However, Celgene acquired Abraxis in 2010 – adding Abraxene to its portfolio and the Phoenix plant to its network – and then in 2019 Bristol Myers Squibb acquired Celgene for $74 billion.

After the acquisition, Bristol Myers selected the 280,000 square-foot Phoenix facility to be transformed into a biologics sterile drug product manufacturing site, with an additional 100-150 personnel added to the current workforce of 300 by the end of 2024.

In response to the warning letter, the FDA has asked Abraxis/Bristol Myers to provide a detailed response that includes a comprehensive risk assessment of all contamination hazards, a CAPA plan, an equipment evaluation, a quality assurance report, and a retrospective evaluation by a qualified third party of investigations and failure modes related to the capability of the aseptic processing operation.