The Form 483 is a further blow to the potential approval of Bristol-Myers Squibb’s lymphoma CAR-T candidate liso-cel, made at the Bothell, Washington facility.
The form comes after the US Food and Drug Administration (FDA) visited the facility between October 7 and 16 and lists six heavily redacted observations made about manufacturing processes.
These include failures in reviewing any unexplained discrepancies and questions around the reliability of Certificates of Analysis (COAs) from third-party vendors; problems with written records of investigations into unexplained discrepancies and written procedures for Manufacturing Material Visual Inspections; issues with procedures designed to prevent microbiological contamination of drug products; and a lack of establishment of scientifically sound and appropriate specifications and test procedures in laboratory controls.
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The form was addressed to Juno Therapeutics, which set-up the facility. Juno was acquired in 2018 by Celgene. Celgene has since been acquired by Bristol Myers Squibb (BMS) for $74 billion.
The facility is one of two run by BMS that manufactures chimeric antigen receptor (CAR) T-cell candidate lisocabtagene maraleucel (liso-cel). The vector is manufactured at an unnamed contract development and manufacturing organization (CDMO) in Texas.
A spokesperson for BMS said the firm “does not have comment on the FDA process or inspection” but pointed us to a press release from November issued to announce the review of the Biologics License Application (BLA) for liso-cel would not be completed by the Prescription Drug User Fee Act (PDUFA) action date of November 16.
Though this statement came a month after the 483 at Bothell, BMS did not accredit the delay in liso-cel’s approval to that inspection, instead referencing the “failure to conduct an inspection of a third-party manufacturing facility in Texas.”
BMS had hoped the product would be approved by the FDA as an anti-CD19 therapy targeting lymphoma by the year’s end, but said in September that the impact of COVID-19 had delayed the FDA inspections at the plants.
FDA approval of liso-cel by December 31, 2020 had been one of the required remaining milestones of the Contingent Value Rights issued upon the close of the Celgene acquisition late last year, but with no new anticipated action date this is likely to be missed.