FDA EIR - Regeneron Pharmaceuticals Inc - October 18, 2019

An FDA inspection of Regeneron Pharmaceuticals Inc.'s Rensselaer, NY facility was conducted from October 9-18, 2019. The inspection focused on current Good Manufacturing Practices (cGMP) for non-sterile bulk and formulated biological drug substances, including Eylea, Kevzara, and Praluent. It was conducted under Compliance Program Guidance Manuals 7356.002M and 7356.021, emphasizing regulatory adherence to 21 CFR Parts 210/211, 600/601/610, and the Federal Food, Drug, and Cosmetic Act.

The main observation, noted on an FDA Form 483, highlighted the company's failure to adequately assess unexpected events potentially affecting the safety, purity, or potency of distributed biological products for regulatory reporting. Verbal discussions also addressed concerns about the timeliness and appropriateness of Corrective and Preventive Action (CAPA) implementation and proactive impact assessments for change controls. Specific issues identified included endotoxin recoveries linked to supplier-related contamination of a processing aid and the use of unsuitable transient sampling tubes for endotoxin testing. There was also an instance of abnormal cytotoxicity during viral screening, where initial documentation was incomplete.

Additionally, certain biological drug substance lots (Dupixent and Eylea) lacked final disposition by the Quality Assurance unit due to open investigations or quality decisions, with one regulatory assessment still pending. Regeneron management was advised to implement voluntary corrective and preventive actions. Failure to do so may result in further regulatory action, with the inspection's final classification pending a complete review of the report and the company's official response.