Lilly Hit on Quality, Lab Controls in New FDA-483
Significant quality and laboratory control issues are cited in a just-posted Form FDA-483 issued to Eli Lilly after an August reinspection at its Imclone manufacturing facility in Branchburg, NJ. The GMP problems could pose a hurdle for a promising Covid-19 drug that will be made there. Last month, Lilly said it had asked FDA for an emergency use authorization (EUA) for its bamlanivimab neutralizing IgG1 monoclonal antibody as monotherapy in higher-risk patients who have recently been diagnosed with mild-to-moderate Covid-19 (see earlier story). Bamlanivimab is similar to Regeneron’s investigational antibody cocktail REGN-COV2 that president Trump was given after contracting the coronavirus earlier last month.
The FDA-483 said that there is a quality failure to “thoroughly review any unexplained discrepancy and the failure of a batch or any of its components to meet any of its specifications whether or not the batch has been already distributed.” For example, FDA said incidents that occurred during GMP activities that may have had an impact on product quality were not investigated. Such incidents were classified as “observations” instead of “deviations” and were closed without documenting all the investigation details, root causes surrounding the issue and implementing corrective actions, the agency said. On the laboratory side, the FDA-483 said lab controls “do not include the establishment of scientifically sound and appropriate test procedures designed to assure that drug substances conform to appropriate standards of identity, strength, quality and purity.”
The reinspection followed an 11/2019 inspection. According to an FDA-483 that was just posted too, appropriate controls are not being exercised over computers or related production systems at the facility. The agency said that electronic files identified as Calibration Study, Qualification Study and Verification Study have been deleted, adding that the “deleted incidents and related audit trail were not reviewed by the quality unit.” Appropriate controls are also not exercised over computers or related laboratory systems, FDA said, specifically identifying quality control laboratory data stored on multiple stand-alone equipment computer systems that are not secured from modification or deletion.
Eli Lilly says it has retained an outside consultant to “conduct a comprehensive independent review of systems” at its Branchburg, NJ site, following two inspections over the past year that have cited significant GMP concerns. “The issues raised during the Branchburg inspections have our full attention and we have been working closely with FDA on remediation efforts,” the company says, adding that “we have increased staffing and resources at Branchburg to manage the additional activity levels we are experiencing related to production of active pharmaceutical ingredients. We are confident that the issues raised during the Branchburg inspections did not impact product quality or patient safety. While Lilly has not received a Warning Letter or other enforcement letter from the FDA related to this matter, we nevertheless take all FDA inspection findings very seriously and are urgently working to address their concerns.”