FDA hits Simtra BioPharma Solutions with warning letter over German site

The U.S. Food and Drug Administration has issued a warning letter to Simtra BioPharma Solutions following the agency’s unannounced inspection of its sterile injectable manufacturing operations in Halle/Westfalen, Germany.

During the FDA’s inspection of the site in September 2025, inspectors identified “significant violations” of current Good Manufacturing Practice (cGMP) regulations for finished pharmaceuticals including those involving contamination, according to the warning letter.

“Your firm failed to perform operations within specifically defined areas of adequate size and to have separate or defined areas or such other control systems necessary to prevent contamination or mix-ups in aseptic processing areas,” states the FDA letter to Simtra CEO Franco Negron.

The agency cited significant deficiencies with aseptic processing controls and restricted access barrier system (RABS) processing lines used to aseptically manufacture sterile drug products for the U.S. market.

“Your firm failed to establish and follow appropriate written procedures that are designed to prevent microbiological contamination of drug products purporting to be sterile, and that include validation of all aseptic and sterilization processes,” the agency said. “Cycles were inadequately validated to ensure that they were capable of consistently decontaminating all interior surfaces … and multiple RABS lines in preparation for aseptic production.”

Between June 2023 and September 2025, the FDA said routine testing of cleaning use points in Simtra’s ISO 5 and RABS resulted in at least 47 microbial recoveries — including 14 that exceeded the company’s action limit — repeatedly recovering organisms including Sphingomonas, Methylobacterium, Bradyrhizobium, and Ralstonia species.

The FDA’s letter warned that Simtra’s failure to address any of these violations may result in the agency refusing to admit products manufactured at its Halle/Westfalen facility to the U.S.

“Product quality and patient safety are our highest priorities,” a Simtra spokesperson said in an emailed statement to Pharma Manufacturing. “We take the agency’s observations seriously and are fully committed to addressing each item promptly and comprehensively. We have already begun implementing corrective and preventive actions and are engaging outside experts to strengthen ongoing remediation efforts.”

Simtra added that it will work closely with the FDA and “continue to provide the agency with periodic updates on the status of these efforts to ensure supply continuity while fully addressing the warning letter observations.”

Halle/Westfalen investments

The New Jersey-headquartered contract development and manufacturing organization (CDMO), which focuses on sterile injectables, is investing in its facilities in Bloomington, Indiana and Halle/Westfalen. In July 2025, Simtra completed the construction of a new $100 million production building at its manufacturing site in Germany.

The expansion added approximately 19,400 square feet of new production space, bringing the site’s total footprint to nearly 130,000 square feet. The company also added a $14 million conjugation and purification suite for antibody-drug conjugates (ADCs), while the new building includes two high-speed isolator lines — one for syringes and one for liquid and lyophilized vials.

Simtra’s Halle investment was meant to support increased demand for fill-finish services, particularly for prefilled syringes and high-potency vial production. The site includes 15 freeze dryers — four added as part of the expansion — used to preserve the stability of sensitive molecules during drug manufacturing.

In June, Simtra signed a five-year strategic alliance with MilliporeSigma, the U.S. and Canada Life Science business of Merck KGaA, Darmstadt, Germany, to support the manufacturing of ADCs. The teaming combines Simtra’s sterile injectable expertise with MilliporeSigma’s capabilities in bioconjugation and payload manufacturing. Under the partnership, ADC drug substance produced by MilliporeSigma will be transferred directly to Simtra for fill-finish, offering customers a turnkey solution.