The FDA is taking complaints about a Bristol Myers Squibb subsidiary’s manufacturing flubs straight to the top.
In an Oct. 31 warning letter addressed to BMS helmsman Giovanni Caforio, the FDA dinged Abraxis Bioscience—acquired by Bristol Myers’ Celgene in 2010—for a raft of production issues tied to the companies’ billion-dollar cancer med Abraxane. BMS got its hands on Abraxane—approved in breast, lung and pancreatic cancer—by way of its $74 billion Celgene buyout back in 2019.
The main issue plaguing Abraxis’ Phoenix, Arizona manufacturing plant—which the FDA inspected from March 28 to April 6, 2022—is the company’s failure to take corrective and preventative steps to return its aseptic processing line and manufacturing operations “to a state of control,” the FDA said in its citation, which the regulator published on its website this week.
Between April and October 2021, Abraxis ran into “[m]ultiple media fill failures” when simulating the aseptic process used to fill Abraxane. Further, Abraxis last December released drug batches “potentially impacted by these failures,” the FDA stated in the warning letter.
The BMS company’s media fill snafus stretch back to last April when the company observed a “very high number” of contaminated units. “Ten different microbes were identified from samples of contaminated units including sporeforming, vegetative, gram-negative and gram-positive microbes.”
When Abraxis conducted a repeat media fill in July 2021, more contaminated units came to the surface, according to the warning letter. Similar problems also cropped up last October and November.
The company’s investigation into the media fill flub was “insufficient,” the FDA said. “Without a comprehensive assessment of contamination hazards and a [Corrective Action and Preventative Action (CAPA) plan] that builds more holistic risk mitigation into your operational design, there is no assurance that you can prevent recurrence of sterility problems due to various latent or active failure modes in your operation."
Despite the FDA chiding, the agency did note Abraxis has taken “significant steps” to right the ship at its Phoenix factory, including filing a Field Alert Report, rejecting suspect batches and suspending operations.
Still, those efforts are “inadequate,” the FDA noted, adding “[t]he recurring incidents of contaminated units in media fills are an indicator of an adverse trend in your aseptic filling line.”
Given the nature of the problems at Abraxis, the FDA has recommended the BMS subsidiary enlist a current Good Manufacturing Practices (cGMP) consultant.
Last year, BMS posted full-year Abraxane sales of $1.18 billion.
After an inspection slowdown fueled in part by the COVID-19 pandemic, the FDA has started releasing manufacturing site write-ups at a steadier pace this year.
Last month alone, the FDA admonished three separate companies over issues related to contamination, equipment problems and sanitary lapses.
Torrent Pharmaceuticals and CDMO Catalent both received FDA Form 483s in October, tied to possible contamination and improper investigations into lab failures, plus problems with air filters and other equipment, respectively.
That same month, Carolina-based Nephron Pharmaceuticals also landed in the FDA’s sights, receiving a warning letter that flagged issues with microbial contamination, cross-contamination, quality control and multiple failures by the company to adequately address problems previously identified by the agency.