FDA Conditions Lilly EUA with GMP Requirements
FDA’s recent emergency use authorization (EUA) for Eli Lilly’s investigational monoclonal antibody therapy bamlanivimab for treating mild-to-moderate Covid-19 in adult and pediatric patients (see earlier story) contains GMP-related conditions the company must maintain due to concerns raised in two inspections conducted at its manufacturing plant in Branchburg, NJ. A recently-posted Form FDA-483 issued after an August reinspection at the company’s Imclone manufacturing facility found that incidents during GMP activities that may have affected product quality were not investigated. In response, a Lilly statement said the company is “working diligently to address a total of four FDA observations from the inspections and [we] have performed in-depth investigations into each of the FDA’s areas of concern.”
Under the EUA, FDA said that Lilly must retain an independent third party to “conduct a review of the batch records and any underlying data and associated discrepancies of bamlanivimab drug substance manufactured at Lilly Branchburg, NJ... If the independent review finds, prior to release, a discrepancy with significant potential to affect critical quality attributes, the product must not be released unless and until the issue is satisfactorily resolved. Any discrepancies found by the independent review, whether prior to or after release, must be reported to the agency in a summary report, submitted every 14 calendar days, and include Lilly’s corrective and preventive action plans for each discrepancy, including whether market action is required. The plans must include an appropriate evaluation of each discrepancy’s potential impact on any released drug substance and associated drug product.”
Lilly’s independent third-party will also need to conduct laboratory release testing of the bamlanivimab drug substance manufactured at Lilly, Branchburg (excluding bioburden and endotoxin testing), according to the EUA. The company also must submit information to the agency within three working days of receipt of “any information concerning any batch of bamlanivimab (whether the batch is distributed or not), as follows: (1) information concerning any incident that causes the drug product or its labeling to be mistaken for, or applied to, another article; and (2) information concerning any bacteriological or microscopic contamination, or any significant chemical, physical, or other change in deterioration in the drug product, or any failure of one or more batches of the drug product to meet the established specifications,” it says.
Additionally, if FDA requests that these, or any other batches, at any time, be recalled, Lilly must recall them, the EUA says. Lilly also must not implement any changes to the description of the product, manufacturing process, facilities and equipment, and elements of the associated control strategy that assure process performance and quality of the authorized product without notification to and concurrence by the agency.