The recent public disclosure of a 'FORM 483' by the U.S. Food and Drug Administration (FDA) regarding Samsung Biologics has triggered widespread interest in whether this development will culminate in the issuance of a 'Warning Letter.' Historically, when the FDA makes a FORM 483 disclosure, it has resulted in a Warning Letter approximately 8% of the time.

As of October 29th, the FDA has documented 191 instances of FORM 483 disclosures, with 15 cases (around 8%) leading to the issuance of Warning Letters. Notably, in the case of Celltrion, they received a FORM 483 in June 2017, publicly disclosed by the FDA, and approximately seven months later, in January 2018, they received a Warning Letter.

Sun Pharmaceuticals, an Indian-based global contract manufacturing organization (CMO), had its FORM 483 publicly disclosed in August 2022, followed by the issuance of a Warning Letter four months later. Similarly, Japanese-based CMO company Toyobo and Indian-based CMO company Intas Pharmaceuticals both received Warning Letters after their respective FORM 483 disclosures in 2021 and 2022.

The timeframe from FORM 483 disclosure to Warning Letter issuance has ranged from a minimum of 2.5 months to a maximum of 8 months, with an average duration of approximately 4 months. Samsung Biologics received its FORM 483 on September 1st, and approximately 2 months have elapsed since that time.

An industry insider stated, "When FORM 483 is issued, the company must respond to the FDA within 15 business days," adding, "It is likely that Samsung Biologics has already submitted a response containing Corrective Actions and Preventive Actions (CAPA)."

The same source explained, "The timeframe for each case until the issuance of the final FDA report, known as the Establishment Inspection Report (EIR), varies," and speculated, "The decision on whether to issue a Warning Letter may be made as early as 2 months or as late as 6 months after the inspection."

On October 17th, the FDA officially disclosed the FORM 483 issued to Samsung Biologics on its website. This FORM 483 lists six items, and some in the industry have interpreted certain aspects, such as inappropriate data integrity management, delay in device revalidation, and inadequate facility management, as potential "violations of basic GMP principles."

Within the industry, there is a difference of opinion regarding the significance of this FORM 483. Some argue that "FORM 483 typically follows inspections," while others believe that "the fact that the FDA chose to disclose Samsung Biologics' FORM 483 suggests a different level of seriousness."

It's important to note that not all FORM 483s are publicly disclosed on the FDA website. The FDA only makes FORM 483 public in cases mandated by the Federal Food, Drug, and Cosmetic Act (FD&C Act) or when there is significant external demand for information disclosure.