Recent FDA Warning Letters Highlight Common cGMP and CAPA Flaws
May 30th, 2025 // 7:04 pm @ jmpickett
FDA keeps itself busy with handing out warning letters in 2025. This week, I noticed that FDA issued warning letters to a pharmaceutical company for not following cGMPs, and a diagnositic company for not implementing proper CAPAs.
AACE Pharmaeuticals – May 13, 2025, Warning Letter
A May 13 warning letter to AACE Pharmaceuticals stated that the drugmaker had marketed eye ointments from Brassica Pharma, an Indian CMO. Early last year, FDA put an import alert on Brassica for not maintaining the correct sterility procedures, phony lab records, and more.
A November 2024 AACE Pharma inspection found the drug company was importing products from Brassica and selling them in the United States without correct controls. FDAers said the quality control unit wasn’t ensuring the redistributed products adhered to cGMP requirements.
The warning letter informed AACE that it used a CMO to make ophthalmic drug products. However, the QC unit didn’t have proper supplier qualification procedures to ensure the drugs obtained from the CMO were made in compliance with Good Manufacturing Practices.
AACE responded to the original 483 early this year, stating it had redone its procedures. But FDA said the company hadn’t given enough details about how it would fix the cGMP flaws. FDA noted that the included procedures didn’t have a process to evaluate other contract organizations, or how to disqualify them for not meeting cGMPs.
FDA stated that comparing a COA from a CMO to pre-approved specs doesn’t overcome the company’s requirement to properly evaluate, qualify, audit, and monitor contract manufacturing companies.
Sedecal S.A. – May 5, 2025, Warning Letter
FDA sent a May 5 warning letter to X-ray maker Sedecal S.A. in Spain for GMP violations. FDA stated that the company started a CAPA after a DXD100 obile self-propelling X-ray device crashed into a control panel, and another report that the device almost struck a patient. But the FDA auditors stated that the firm didn’t document its risk assessment of the medical devices in use that have the problem.
Sedecal was also warning for not establishing device design validation procedures. FDA stated that design validatin must include risk analysis, if needed. Sedecal did a recall to address the accidental movement of the X-ray machine that could cause severe injury. However, the risk analysis in April 2022 didn’t include higher hazard severity to make sue that proper risk control measures were taken.
Sedecal told FDA it would update its CAPA procedures to ensure subsequent investigations are correctly documented, workers are trained, and the recall process is reviewed. FDA stated the responses weren’t acceptable because they didn’t mention the revised procedures and a review of necessary documents.
How Common Are Improper Sterility Procedures?
I’ve seen many FDA 483s and warning letters this year. I wondered how many improper sterility procedures are flagged in FDA inspections. Unfortunately, FDA doesn’t publish numbers for improper sterility procedures and poor hygiene practices.
However, we know that sterility issues are a common FDA inspection concern, especially for sterile drugs. My review of FDA reports and data suggests that deviating from cGMPs for sterility-related issues – including inadequate aseptic processing, insufficient validation of sterilization processes, or failure to maintain sterile equipment – are some of the more serious 483 and warning letter red flags. For instance, in 2023, the agency performed 620 foreign and 444 US-based inspections, and sterility-related observations were often noted in warning letters and 483s. These observations were quite common at plants making sterile biologicals and injectables.
One sterile drug maker had 100 batches contaminated in 180 days, while another had 25 batches in the same period. This shows how serious a systemic sterility problem can be. When there’s a sterility lapse, consequences can be serious – a recall or OAI letter can be in play. Keep in mind that FDA continues with its risk-based approach to inspections; firms making sterile drugs can anticipate an inspection every 24 to 36 months.
Foreign plants in India and China often have more cGMP violations, including sterility problems, often because of infrequent FDA audits or improper internal controls. Overall, sterility issues aren’t that common, but when they happen, it’s bad news, and the FDA takes them very seriously.
We’ll add a post soon about ensuring your sterility procedures align with cGMPs. In particular, quality teams should understand FDA 21 CFR Part 211, EU GMP Annex 1, and ISO 14644.
