Bizarre Findings in FDA Warning Letters

The ECA regularly reports on FDA Warning Letters that are published on the FDA website following an FDA inspection and that identified deficiencies. These may be statistical overviews of a fiscal year. Alternatively, individual findings may be discussed and then analysed in a news item. In addition, the corrective measures required by the FDA are often listed in the news. Below is an overview of 'bizarre' findings by the FDA, particularly from last year.

Premises and Equipment

In the past, Warning Letters have repeatedly cited rusty equipment and/or product residues from previous products or other products when facilities are also used for non-pharmaceutical products. See also the section on cleaning validation below. One Warning Letter criticised the transfer of equipment and vials between Class A and B without smoke studies. However, smoke studies that were carried out showed air turbulence caused by the transport trolley. Why does the company continue to use this procedure with the transport trolley when it can already see from the smoke studies that there are problems?

Quality Control

But even in the laboratory, there have been some 'bizarre' inspection results in the past. In one case, for example, the impurities were only analysed according to the Chinese pharmacopoeia, without demonstrating that the method was equivalent to methods in the US pharmacopoeia. In another case, the impurities were not monitored at all in the stability studies. So why did the company conduct these studies?

Process and Cleaning Validation

Companies are repeatedly criticised by the FDA for not performing process validation and/or cleaning validation. In some cases, 'only' the absence of stage 3 of the process validation life cycle (continued process verification) is criticised. The current FDA process validation guideline has been in effect since 2011... The issue of cross-contamination has been mentioned in the 21 CFR 211 version since 1978, and the FDA Guide to Inspection on Cleaning Validation dates back to 1993.

Aseptic Manufacturing

'Bizarre' deficiencies are also frequently found in the aseptic area. For example, a Warning Letter criticised an employee for touching the inside of sterile tubes. In addition, not all of his skin was covered. In another case, the media fills were not reviewed for microbiological growth. No wonder it was passed. 

Documentation

Documentation is a 'fertile field' for bizarre Warning Letter findings. Often in connection with data integrity problems. For example, values on a worksheet were approved by a person who was not physically present. In another case, reports were regularly generated by the only trained analyst ('fabrication data'). In another case, data in a report was arbitrarily supplemented, signatures backdated and pages exchanged. And all this with the acquiescence of quality assurance, quality control, research and development and production managers. In another case, the timely documentation in the laboratory was criticised. A microbiological evaluation plate was found in the waste, but the results were not documented. The lab technician's laconic response was, 'I have the results in my head.' Similarly, in one company, reports of QA oversight errors were found in a bag under a trolley next to a waste bin. In another case, the FDA investigator was unable to view QC data because a lab technician had taken the only computer containing the data home with him. Even state-of-the-art technology can have its 'pitfalls': in this case, analysis certificates were sent via WhatsApp to an employee's mobile phone. However, this employee deleted the certificates.

But there are also 'general findings'. In one case, an inspected company refused the FDA access to its laboratories. Some companies do not respond to FDA letters or do not include replies in English.

Conclusion

Even though some of these bizarre findings seem almost funny, you wouldn't want to buy products from these companies yourself.