The FDA has recently issued a series of warning letters to pharmaceutical companies, highlighting significant violations of Current Good Manufacturing Practice (CGMP) regulations. These letters, released in September 2024, detail a range of issues from contamination and inadequate quality control to deviations from approved manufacturing processes, raising concerns about patient safety and product quality.
CARsgen Therapeutics: Contamination and Monitoring Lapses
CARsgen Therapeutics, a manufacturer of autologous CAR T cells, received a warning letter citing a fly infestation within its manufacturing facility. According to the FDA, the company's Quality Assurance team observed a box of food covered in scuttle fly pupae in the mechanical room housing air handling units. This incident was followed by the discovery of scuttle fly larvae in multiple environmental and personnel monitoring samples collected in the cleanrooms. The FDA also noted the company's failure to conduct non-viable particulate monitoring and viable microbial active air monitoring during open manufacturing. Furthermore, CARsgen's Senior Vice President of Quality admitted that the firm had not conducted cleaning validation, a critical step in ensuring product purity.
Berkeley Biologics: Donor Screening Deficiencies
Berkeley Biologics, previously operating as Elutia, Inc., faced scrutiny for manufacturing and distributing viable bone matrix products without adequate donor screening. The FDA's warning letter highlighted the company's failure to determine the ineligibility of deceased donors with a documented medical diagnosis of sepsis. Tissues from these donors were then manufactured into Fiber Viable Bone Matrix (FVBM) and Osteo Viable Bone Matrix (OVM) and distributed for implantation, some of which were associated with an outbreak of Mycobacterium tuberculosis infections. This lapse in donor screening poses a significant risk of transmitting infectious diseases to patients.
Zydus Lifesciences: Cross-Contamination and Aseptic Issues
Zydus Lifesciences, an India-based pharmaceutical company, received a warning letter addressing multiple instances of cross-contamination due to inadequate cleaning of shared equipment. The FDA noted that the company's initial cleaning study failed to assess the adequacy of cleaning methods for a specific drug product that was later found to be "stickier" on product contact surfaces. Additionally, batches were released despite out-of-trend contamination being identified in related batches, without a sufficient rationale for the representativeness of the samples tested. The warning letter also cited issues with glass particulate contamination and poor aseptic behavior among employees, further compromising product sterility.
TJA Health: Raw Material Testing Deficiencies
TJA Health in Illinois was cited for not testing incoming raw materials, including those considered high-risk for diethylene glycol (DEG) and ethylene glycol (EG) contamination. Instead, the company relied on the supplier's certificate of analysis, a practice deemed insufficient by the FDA. The company was also found to be using water as a component in non-sterile drug products without demonstrating adequate control for microbial contamination, increasing the risk of product contamination and potential harm to patients.
These warning letters underscore the FDA's commitment to enforcing CGMP regulations and ensuring the safety and quality of pharmaceutical products. Companies receiving such letters are required to take prompt corrective actions to address the identified deficiencies and prevent future violations. Failure to comply can result in further regulatory action, including product recalls, import alerts, and injunctions.
