FDA says Abraxis failed to proactively address repeat media fill contamination issues
The US Food and Drug Administration (FDA) blasted Abraxis Biosciences in a recent warning letter for not addressing recurring media fill failures in its aseptic processing operations of the sterile drug Abraxane and for failing to conduct robust follow-up investigations to determine the root cause of these multiple failures.During a one-week inspection conducted in late March at the firm’s site in Phoenix, AZ, the agency observed “multiple media fill failures” in the firm’s aseptic processing operations on the filling line used for Abraxane (paclitaxel), an oncology drug.
The company experienced media fill failures in April 2021 and observed “a very high number” of contaminated units. Ten different microbes were identified from contaminated samples including sporeforming, vegetative, gram-negative and gram-positive microbes.
In July 2021, a repeat media fill also found “multiple” contaminated units. The firm attributed the root cause to personnel gowning, poor disinfection of the Restricted Access Barrier Systems (RABS) and contaminated forceps used in the RABS stopper bowl.
The agency reprimanded the firm for not expanding the scope of the investigation to include a “more holistic remediation” of the root cause of the problem, such as evaluating the frequency, specificity, and robustness of their RABS disinfection program.
Media fill failures were again observed again in October and November 2021. Yet, in December, the firm released batches potentially impacted by these failures.
These media fill contamination issues indicate that “your aseptic manufacturing operations were not in control,” FDA wrote. “Without a comprehensive assessment of contamination hazards, and a CAPA 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.”
FDA acknowledged the company took “significant steps” to address the media fill failures by submitting a Field Alert Report, rejecting batches and suspending operations. Yet this response was inadequate because the company “continued to observe contaminated units in subsequent media fills. The recurring incidents of contaminated units in media fills are an indicator of an adverse trend in your aseptic filling line.”
FDA strongly recommended that the firm hire a GMP consultant.
The agency warned the company that failure to address these violations could result in the agency withholding approval of new applications.
The warning letter was posted on 8 November; the company is a subsidiary of Bristol Myers Squibb.
Warning Letter
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