The FORM 483 recently issued by the FDA to Samsung Biologics has drawn attention due to its connection to the approval process for a customer's new product. Notably, in some overseas cases, the mere issuance of FORM 483 has resulted in the rejection of new product approvals, creating significant interest in this matter.

The FORM 483, disclosed by the FDA on October 17th, listed the lack of data integrity management within the MSAT (Manufacturing Science and Technology) department as the primary point of contention. A closer examination of this issue reveals its connection to the submission data for the customer's product approval. The document highlighted shortcomings in ensuring data integrity ("The MSAT laboratory was used in support of application submission data for [redacted] and [redacted]…having inadequate controls in assurance of data integrity").

Samsung Biologics confirmed that the recent issuance of FORM 483 by the FDA is indeed tied to a product approval process. In response to HitNews' inquiry regarding the connection between the FDA inspection and product approval, a company representative confirmed the link, stating, "Yes," while also noting, "However, it's difficult to disclose which product was involved."

The FDA typically conducts an initial inspection of a manufacturing facility when receiving a new product approval application for a specific product. If any irregularities are observed during this process, the FDA documents them in FORM 483 and issues it. In cases where the inspection rating is "Official Action Indicated (OAI)," a Warning Letter is issued.

However, the FDA can reject a product approval application without issuing a Warning Letter following FORM 483, as demonstrated by recent rejections of Biologics License Applications (BLAs) for Regeneron, Teva, and Alvotech.

In June 2022, the FDA rejected Regeneron's application for high-dose aflibercept (marketed as Eylea) approval, citing issues with the contract manufacturing organization (CMO) Catalent, which manufactures the product. During the FDA's inspection of Catalent, deficiencies in facility management, non-compliance with standard operating procedures (SOP), and inadequate device revalidation were identified, leading to the public release of FORM 483 on the FDA's official website.

Teva and Alvotech faced similar challenges. The FDA rejected their application for approval of the STELARA biosimilar 'AVT04 (development code)' last month, highlighting inappropriate management practices discovered during the initial inspection conducted in March. The FDA also issued FORM 483 in this case, making it public.

Following inspections carried out by the FDA in August and September, FORM 483s were issued to Samsung Biologics. On October 17th, the FDA officially released FORM 483 on their website, revealing six identified deficiencies, including inadequate facility management, non-compliance with standard operating procedures, inadequate device revalidation, and inappropriate data integrity management.

Some industry experts have responded by emphasizing the importance of adhering to basic GMP (Good Manufacturing Practices) principles. Additionally, they've noted the unusual involvement of a high number of FDA investigators (5 individuals) in this inspection. An industry insider commented, "While not all FORM 483s lead to Warning Letters, they can influence new product approvals," and added, "If this issue is linked to new product approvals, the FDA is likely to take action."

In response, Samsung Biologics issued an official statement, stating, "The receipt of FORM 483 does not necessarily indicate serious flaws in our processes or unresolved issues." A company representative also emphasized, "The issuance of FORM 483 does not impact product quality or patient safety, and we want to stress that fact."