The publication of a US FDA Form 483 reveals failures to implement sustainable corrective action and preventive action, and inadequate maintenance at a Catalent fill/finish facility.

Earlier this month, we broke the news that contract development and manufacturing organization (CDMO) Catalent received a Form 483 at its European syringe filling facility in Brussels, Belgium.

While the issues observed allegedly caused disruption in the supply of Novo Nordisk’s weight loss drug Wegovy (semaglutide), specific details were sparse. But this week, the US Food and Drug Administration (FDA) has published the results of the inspection, which took place between the 18^th and 26^th October last year.

Image: Stock Photo Secrets

The seven observations from the drug product plant include failures to thoroughly investigate unexplained discrepancies or batch failures, with multiple deviations associated with HEPA (high-efficiency particulate absorbing) filter failures being cited by the Agency.

“Other GMP manufacturing areas have a similar elevated level of HEPA filter failures, with the root cause of the HEPA filter failures unknown. There is no CAPA in support of correction action. Your firm failed to ensure your investigations identify appropriate root causes and you failed to implement sustainable corrective action and preventive action (CAPA).”

Other observations include failure to establish written procedures for production and process control, the non-establishment of validation designed to prevent microbial contamination of the sterile drug product, and inadequate written procedures to prevent contamination.

In the heavily redacted fifth observation, the FDA said equipment and facilities used in the manufacture of drug product were not adequately maintained or appropriately designed to facilitate operations for their intended use by Catalent. Within the text, the Agency said two black lines were observed on a mechanical piston system, the cause of which was unknown.

A Catalent spokesperson confirmed to this publication that the FDA’s observations at the Brussels sterile filling facility stemmed primarily from local HEPA filter system test deviations.

“Catalent takes all FDA observations seriously, and we have developed a comprehensive plan to address the observations as quickly as possible. This plan is now in the process of being implemented and reviewed with customers and regulatory authorities.”

The full 483 can be found below.

Catalent Belgium, Brussels,… by Dan Stanton