FDA cites contamination concerns in warning to Sanofi MA plantFDA cites contamination concerns in warning to Sanofi MA plant

Issued on January 15, the Warning Letter followed a US Food and Drug Administration (FDA) inspection at the facility – located 30 km west of Boston, Massachusetts – in June and July last year and highlighted numerous deviations from current Good Manufacturing Practice (cGMP) for drug substance production.

“FDA documented that approximately 20 percent of bioreactor runs attempted between January 2022 and July 2024 were rejected for contamination or other quality failures,” the Agency wrote. “This rate is excessive and calls into question the state of control of your process.”

Accusing Sanofi of failing to conduct adequate investigations into these critical deviations, including multiple microbiological contamination events, the letter cited inadequate investigations of particle presence within several lots of an undisclosed drug substance as an example. Inadequately investigating product leakage was also noted during the audit.

Other deviations mentioned in the letter include Sanofi’s failure to demonstrate that the manufacturing process can reproduce an active pharmaceutical ingredient (API) with its predetermined quality attributes, and a failure in using appropriate equipment for the manufacture of specific drug substance:

“Mobile carts used in the setup of [undisclosed] units required operators to get down to the floor and manually lock and unlock the cart brakes despite previously determining equipment proximity to the floor as a contributing root cause in microbiological contamination events.”

In another example, the Agency wrote: “[Undisclosed equipment] used to establish temporary sterile boundaries for tubing continue to be used despite being identified in a June 2023 microbial contamination event investigation as possessing a ‘design flaw’ that may allow microbial ingress.”

The FDA also cited failures within the facility’s quality unit. Sanofi responded last year by identifying four contributing root causes – “excessive personnel attrition of trained investigators, process knowledge gaps amongst newer investigators, prioritization of investigations associated with lots pending release, and inconsistent communication of ‘deviation performance metrics’” – but was pulled up further by the Agency due to insufficient detail as to how these causes are to be corrected.

The FDA has requested Sanofi to respond to it with corrective action plans within 15 days.

When contacted, a Sanofi spokesperson told us: "Patient safety and the quality of our products are our highest priorities. We take all inspections extremely seriously and we are fully committed to working with the FDA to resolve all findings holistically, robustly and promptly to meet the agency’s requirements and expectations."

They added there has been "no interruption to manufacturing or to the continued supply of medicines from the Framingham site as a result of these findings."

Framingham

The Framingham site, commissioned by Sanofi acquisition Genzyme, won approval from both the FDA and European Medicines Agency (EMA) in 2012 for the production of Fabrazyme (agalsidase beta).

At the time, there had been a shortage of the enzyme replacement therapy – first approved in 2003 to treat the inherited disorder Fabry Disease, a deficiency of the enzyme alpha galactosidase A – due to a series of contamination issues at another Genzyme’ facility: Allston Landing, located close to the Framingham site.

The transfer to Framingham allowed Sanofi to rectify shortages of both Fabrazyme and Cerezyme (imiglucerase for injection) – the latter by freeing space up at Allston Landing.

In 2013, Sanofi invested $80 million to build a downstream facility at Framingham dedicated to Fabrazyme. Since then, Sanofi describes Framingham as "among the world’s first digitally enabled facilities to use continuous-biologics-production technology," in its literature. "Its end-to-end platform uses millions of points of data captured by sensors to continuously optimize for excellence." 

As for the Allston Landing facility, Sanofi sold the plant to contract development and manufacturing organization (CDMO) Resilience in 2021.