FDA Warns Sanofi About API CGMP Deviations, Issues Clinical Hold on Atara Immunotherapies

FDA has issued a warning letter to Sanofi summarizing “significant deviations” from current good manufacturing practice (CGMP) for APIs based on inspections conducted from June 12 to July 9, 2024, at Genzyme Corporation, a subsidiary of Sanofi which acts as a company drug manufacturing facility, in Framingham, Mass. (1). The letter, sent Jan. 15, 2025, amends and replaces one sent Dec. 16, 2024.

In a separate action announced Jan. 21, 2025, FDA placed a clinical hold on active investigational new drug (IND) applications by Thousand Oaks, Calif.-based Atara Biotherapeutics (2). The affected INDs include Ebvallo (tabelecleucel), a monotherapy for adults and pediatric patients two years of age and older with Epstein-Barr virus positive post-transplant lymphoproliferative disease, and ATA3219, an allogenic CD19-targeted chimeric antigen receptor (CAR)-T-cell therapy for treatment of non-Hodgkin’s lymphoma and systemic lupus erythematosus.

In Sanofi’s case, FDA said failure to address the deviations—which it said have the end result of adulterating APIs under section 501(a)(2)(B) of the Federal Food, Drug, and Cosmetic Act—could result in “regulatory or legal action without further notice,” or for FDA to withhold issuance of Export Certificates, or approval of new applications or supplements. A previous response, delivered on July 29, 2024, was considered to be inadequate, for numerous reasons expanded upon by FDA in its letter.

Chiefly, FDA estimated that 20% of bioreactor runs attempted at the Genzyme facility from January 2022 to July 2024 were rejected for quality failures, including contamination (1).

With regard to Atara, a company press release said the clinical hold for Ebvallo was directly connected to GMP compliance issues previously identified in a third-party manufacturing facility pre-license inspection, which were inadequately addressed (2). Starting materials used in the production of ATA3219 are affected by these issues, even though that drug product is manufactured elsewhere.

“We intend to work closely with [FDA] to address these issues as expeditiously as possible,” said Cokey Nguyen, PhD, Atara president and chief executive officer, in the press release. “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’s partnership with Scribe Therapeutics, which combines Scribe’s proprietary clustered regularly interspaced short palindromic repeats editing technologies with Sanofi’s targeted, non-viral delivery technologies, was reported on Jan. 13, 2025 to have reached a success milestone amid a deal that makes Scribe eligible for payments of more than $1.2 billion total for achieving certain benchmarks (2).

Atara—Ebvallo specifically—was given clearance by the European Medicines Agency to be quality control tested at a Thousand Oaks cell therapy manufacturing facility operated by FUJIFILM, the completion of an expansion of which was announced in November 2024 (4). The FDA action does not affect the FUJIFILM facility (2).

References

1. FDA, Warning Letter 320-25-22, Sanofi, amended (CDER, January 2025).
2. Atara Biotherapeutics. Atara Biotherapeutics Provides Update on Clinical Programs Related to Ebvallo (tabelecleucel) and ATA3219. Press Release. Jan. 21, 2025.
3. Scribe Therapeutics. Scribe Therapeutics Achieves Milestone for In Vivo Program in Collaboration with Sanofi. Press Release. Jan. 13, 2025.
4. FUJIFILM. FUJIFILM Diosynth Biotechnologies Celebrates the Expansion Completion at its California Cell Therapy Facility. Press Release. Nov. 20, 2024.