FDA Issues Warning to Sanofi for API CGMP Deviations; Clinical Hold Placed on Atara Biotherapeutics
核心洞察
The FDA issued a warning letter to Sanofi, citing significant deviations from CGMP standards at its Genzyme facility, potentially leading to regulatory actions.
Atara Biotherapeutics faces a clinical hold on its IND applications, including Ebvallo and ATA3219, due to GMP compliance issues at a third-party manufacturing site.
Atara Biotherapeutics is collaborating with the FDA to address the issues and aims to submit the necessary data for the release of the clinical hold, prioritizing patient safety.
The FDA issued a warning letter to Sanofi on January 15, 2025, citing "significant deviations" from current good manufacturing practice (CGMP) for active pharmaceutical ingredients (APIs) at its Genzyme Corporation subsidiary in Framingham, Mass. The inspection, conducted between June 12 and July 9, 2024, revealed that the deviations could result in the adulteration of APIs, potentially leading to regulatory or legal action, withholding of Export Certificates, or rejection of new applications. The FDA deemed Sanofi's previous response, submitted on July 29, 2024, as inadequate. The agency estimated that 20% of bioreactor runs at the Genzyme facility from January 2022 to July 2024 were rejected due to quality failures, including contamination.
Atara Biotherapeutics Clinical Hold
In a separate announcement on January 21, 2025, the FDA placed a clinical hold on active investigational new drug (IND) applications by Atara Biotherapeutics. The hold affects Ebvallo (tabelecleucel), a monotherapy for adults and pediatric patients two years of age and older with Epstein-Barr virus positive post-transplant lymphoproliferative disease (搜索) (EBV+ PTLD), and ATA3219, an allogenic CD19 (搜索)-targeted chimeric antigen receptor (CAR)-T-cell therapy for treatment of non-Hodgkin’s lymphoma (搜索) and systemic lupus erythematosus (搜索).
Atara Biotherapeutics stated that the clinical hold on Ebvallo is directly related to GMP compliance issues identified during a pre-license inspection of a third-party manufacturing facility. These issues were not adequately addressed. Although ATA3219 is manufactured elsewhere, the starting materials used in its production are affected by these same issues.
Company Statements and Future Plans
Cokey Nguyen, PhD, President and Chief Executive Officer of Atara, stated, "We intend to work closely with [FDA] to address these issues as expeditiously as possible. We are encouraged with ongoing correspondence with the agency and a potential path to submitting the necessary data to release the clinical hold. Patient safety remains our priority and maintaining the highest standards for our programs."
Sanofi and Scribe Therapeutics Partnership
Sanofi's partnership with Scribe Therapeutics, which combines Scribe’s proprietary clustered regularly interspaced short palindromic repeats (CRISPR) editing technologies with Sanofi’s targeted, non-viral delivery technologies, achieved a success milestone. Scribe is eligible for payments exceeding $1.2 billion for achieving specific benchmarks.
Ebvallo Manufacturing
Ebvallo was granted clearance by the European Medicines Agency (EMA) to undergo quality control testing at a FUJIFILM-operated cell therapy manufacturing facility in Thousand Oaks. The expansion of this facility was completed in November 2024. The FDA action does not affect the FUJIFILM facility.