Sanofi issued warning letter for Genzyme cGMP failures

French drugmaker Sanofi received a warning letter from the US Food and Drug Administration (FDA) last week for failing to comply with its current good manufacturing (cGMP) requirements for active pharmaceutical ingredients (API). The agency said the company needs to empower its quality unit to take steps to stay in regulatory compliance.

In a warning letter dated 15 January, the FDA wrote that it had serious concerns about manufacturing issues with Sanofi’s former subsidiary Genzyme Corporation’s manufacturing facility in Framingham, MA. Sanofi fully absorbed the company in 2022.

Investigators said Sanofi’s methods, facilities, or controls for manufacturing, processing, packing, or holding failed to meet the agency's regulatory requirements. More specifically, the company was cited for failing to investigate all critical deviations in its manufacturing practices.

Investigators noted that between January 2022 and July 2024, 20% of Sanofi’s bioreactor runs were rejected due to contamination and other quality failures. However, according to FDA, the company failed to investigate the critical deviations adequately.

“Your investigations failed to identify all potential contributing causes, did not consider the conclusions of an engineering study that contradicted your assigned root cause for the [out-of-specification] appearance events, and did not document all investigational activities, including the collection of at least one sample found in a storage room by FDA investigators,” according to the warning letter.

FDA investigators said Sanofi failed to show that its manufacturing process can reliably reproduce APIs that meet its predetermined quality requirements. They said the company repeatedly deviated from its validated manufacturing process in some circumstances.

“When significant variability is observed in a drug manufacturing process or in its input materials, it is essential for executive management to support and implement effective actions to promptly address the source(s) of the variation and ensure a continued state of control,” FDA wrote.

Sanofi was also cited for using equipment that investigators deemed unsuitable for use in microbiologically controlled manufacturing environments. Investigators said mobile carts and equipment to establish temporary sterile boundaries were unsuitable for manufacturing. While the company responded to the concerns by stating they are assessing design improvements to the carts and additional personnel training, FDA said the response was inadequate.

FDA investigators said they had found approximately 84 open and past due deviation investigations through the end of June 2024 that Sanofi's quality unit failed to address to ensure their facility was CGMP compliant. The company said the issue was that a significant portion of its trained investigators had left, newer company investigators had process knowledge gaps, lots pending release were prioritized, and there were inconsistencies in how deviation performance metrics were communicated within the company.

FDA listed several steps Sanofi should take to address the issues with the pending deviation investigations, including developing a comprehensive assessment and remediation plan to ensure its quality unit has the authority and resources it needs and reviewing the appropriateness of its procedures.

“Significant findings in this letter indicate that your [quality unit] is not able to fully exercise its authority and/or responsibilities,” FDA wrote. “Your firm must provide the [quality unit] with the appropriate authority and sufficient resources to carry out its responsibilities and consistently ensure drug quality.”

Finally, FDA investigators cited Sanofi for failing to ensure that all its product deviations are reported and evaluated, critical deviations are investigated, and their findings recorded.

Sanofi was given 15 business days to respond to FDA’s warning letter.

Warning letter

Sanofi issued warning letter for Genzyme cGMP failures

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