Experts offer advice on avoiding common warning letter citations

Experts said that good manufacturing practice (GMP) violations, including inadequate procedures, insufficient training, and problems with data integrity, were commonly cited by US Food and Drug Administration investigators during drug and medical device facility inspections and offered advice on how to avoid enforcement actions related to these violations.

The experts spoke at a webinar sponsored by ProPharma and Hyman Phelps and McNamara, which focused on inspection readiness and avoiding common pitfalls during FDA inspections. It also discussed typical FDA inspection findings and strategies to prevent them.

Simona Mills, senior director of quality and compliance at ProPharma, opened the webinar by defining inspection-readiness. “First and foremost, it involves knowing your job and performing it well every single day. It also means ensuring that your procedures are clear, concise, and accurate. When this is the case, you will likely have little explaining to do when the FDA is on site.”

Eric Plummer, associate director of quality and compliance product lifecycle management at ProPharma, explored specific issues highlighted in FDA warning letters. He noted that a lack of adequate written procedures is a common theme in many warning letters, and this violation was found in 71% of citations from 2015 to 2025.

This deficiency is a general term used in inspections and can fall into various citation categories. These include, for devices, 21 CFR 820.100(a) regarding the lack of or inadequate procedures; for devices, 21 CFR 820.198 concerning the lack of or inadequate complaint procedures; and for drugs, 21 CFR 211.22(d), which refers to procedures not being in writing or not fully followed.

Plummer said that a common observation in warning letters is that some SOPs “read more like a policy than procedure.” This can lead to confusion when the SOPs are too general, making it difficult to understand how the procedures are put into practice. This can be avoided by using clear and concise language and writing the procedures in an active voice when authoring these documents.

He noted that “we also see a fair number of contradictions between procedures.” This can occur when the same topic is covered in multiple procedures, which may not always align. An example is where a quality SOP may have information that contradicts the manufacturing SOP.

To avoid this problem, manufacturers should develop “clear and comprehensive” SOPs that provide enough detail and are not overly standardized.

Another common issue identified in warning letters from fiscal years 2009 to 2025 is inadequate employee training, according to Kalie Richardson, an attorney with Hyman, Phelps & McNamara. For pharmaceuticals, the relevant citations include 21 CFR 211.25(b), which pertains to supervisor training, and 21 CFR 211.259(a). For medical devices, the applicable citation is 21 CFR 820.25(b).

Richardson said that “training is the low hanging fruit of inspections. FDA is always going to request some subset of training records.”

She said that to avoid a training observation, sponsors should develop training materials that are specific to the job role. In addition, manufacturers should keep training records on site and should periodically evaluate the effectiveness of the training and have a process for retraining if necessary.

Eric Good, the director of compliance and quality at ProPharma, stated that another significant issue identified in inspections is the lack of integrity in data. To prevent this problem, sponsors should follow the data integrity principles of ALCOA when managing both paper and electronic records. The term ALCOA means records must be attributable, legible, contemporaneous (or recording data at the time of the event), original, and accurate.

Paper records should have handwritten signatures. To enhance legibility, printed signature logs can be used. "Contemporaneous" means that data should be recorded immediately, while "original" indicates that there can be crossed-out errors. For electronic records, user stamps or e-signatures can be used, along with automated reports, time stamps, audit trails, and data validation measures.

Good said that manufacturers should also ensure they have robust data validation controls to ensure the data is secure with strong authentication and authorization controls and restrict access to data based on user roles and responsibilities.

Good mentioned that he was present during an inspection, during which FDA inspectors discovered a raw data report that had been mistakenly thrown into the shred bin. Although the company discarded it by accident, it was too late to rectify the situation. As a result, the company received a warning letter citing data integrity violations.

He was present at another inspection where the firm received a reprimand for placing a unique password sticker on a computer. The password was "MickeyMouse123." Good stated that FDA inspectors should not be finding these problems. "It's so simple, folks. It's not a complicated system. We should be improving, but we are not."

Experts offer advice on avoiding common warning letter citations

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