FDA Warning Letters: September 2024 Edition
Here’s a look at recent violations cited in FDA Warning Letters: fly pupae, cross contamination, trial dosing errors, and more
Stephanie Vine | | 3 min read | Opinion
Fly infestation
“On July 14, 2023, your Quality Assurance team observed a box of food from June 16, 2023, covered in scuttle fly pupae in the mechanical room which houses the air handling units and failed to remove the box of food until July 31, 2023. After this event, scuttle fly larvae were found in ten environmental and personnel monitoring samples collected in the cleanrooms in July 2023. Additionally, on July 26, 2023, in Suite (b)(4) Clean Room (b)(4) (Grade (b)(4)) a living scuttle fly was observed on the tube rack.”
CARsgen Therapeutics, which manufactures autologous CAR T cells, suffered a fly infestation, and was found to be lacking non-viable particulate monitoring and viable microbial active air monitoring during open manufacturing. The company’s Senior Vice President of Quality also confessed that the firm had not conducted cleaning validation.
Lack of donor screening
Despite not having a BLA and not conforming to cGMP, Berkeley Biologics (which operated under a different name during the inspection) has been manufacturing and distributing viable bone matrix products (Fiber Viable Bone Matrix (FVBM) and Osteo Viable Bone Matrix (OVM), among others) to medical facilities across the US. Among other issues noted in the warning letter, there was a lack of adequate donor screening. The letter states: “For example, you failed to determine as ineligible (b)(4) deceased donors who have a documented medical diagnosis of sepsis…Tissues from these donors were manufactured into FVBM and OVM, and distributed for implantation into patients/recipients, some of which were associated with an outbreak of Mycobacterium tuberculosis infections.”
Sticky products and cleaning
Multiple issues were observed at India’s Zydus Lifesciences, which has recently been involved in voluntary recalls. The company has experienced a number of cross-contamination events because of inadequate cleaning of shared equipment. “Notably, your initial cleaning study failed to assess whether your cleaning methods were adequate to clean (b)(4) drug product, which you later found to be “stickier” on product contact surfaces,” the letter stated.
Batches were released despite out-of-trend contamination being identified in related batches. The letter added, “You provided no rationale for how the samples tested were representative of the potential for overall batch contamination.”
There were also issues with glass particulate contamination and poor aseptic behavior amongst employees.
Failure to test: DEG and EG
TJA Health in Illinois has not been testing incoming raw materials, including those considered to be at high risk for DEG and EG contamination. Instead, the company has been relying on the supplier’s certificate of analysis. The company was also found to be using water as a component in non-sterile drug products, without demonstrating that the water was controlled for microbial contamination.
Wrong dose in pediatric patient
A clinical investigator based at the Clinical Integrative Research Center of Atlanta received a warning letter after a 15-year old female in the trial received 10 times the maximum daily dose in error. No adverse events were reported thankfully and the site took immediate action as soon as the mistake was identified. A warning letter was still issued because the FDA wanted to see details about a corrective action plan to prevent similar mistakes in the future. “Given the significance of the protocol violation involving a pediatric subject, we request follow-up documentation regarding the procedure implemented at your site to ensure compliance with study protocol dosing procedures,” the letter stated.
Ophthalmic issues
Regenerative Processing Plant in Florida has been manufacturing and distributing ophthalmic products that aren’t approved as drugs and that use inappropriate ingredients. The FDA observed that certain products did not conform to Over-the-Counter Monograph M018: Ophthalmic Drug Products for Over-the-Counter Human Use and were formulated with sodium chloride as an active ingredient, which is not permitted for ophthalmic demulcents.
There were also manufacturing issues. For example, processes and cleaning procedures were not validated; contaminated batches were not evaluated for an assignable cause of contamination; media fill data were unreliable; and systems for environmental monitoring were inadequate.
The warning letter also noted that the company had represented its products as being “in full compliance with the FDA.”
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