​Recent Warning Letters Contain Two New Trends

Original Post Date: December 17, 2010
Author: John English

Recent warning letters have contained two new trends and they have been repeated this week. The first is still rare but it is the inclusion of a cease to market order in the warning letter itself. The second is an enhanced FDA comment about what the letter does and doesn’t say about “your facility.”

Several times so far this year, FDA warning letters have included a ‘cease to market’ order. These orders have usually been for “off-shore” companies, although the last one referenced in this group was for a NY-based contract manufacturing company. Another warning letter has just been made available (14 DEC2010) for a domestic company that produces diagnostic assays, a CDRH regulated product. The text is quite to the point:

FDA requests that FIRM NAME immediately cease marketing, promoting, and distributing all in vitro diagnostic products that require PMA approval or 510(k) clearance without FDA approval or clearance. The adequacy of your corrective actions will be evaluated during our next inspection…..

It may be a coincidence that the other US-based example had issues related to testing as well but that one was under CDER. (Integrity of test results is certainly a key FDA focus point – whether the results are “traditional” or electronic.) This new letter also contains another item – it is one of two this week that includes a new ‘disclaimer’ if you like.
Warning letters usually contain a summary text that is similar to the following (also posted 14 DEC 2010):

Finally, you should know that this letter is not intended to be an all-inclusive list of the violation(s) at your facility. It is your responsibility to ensure compliance with applicable laws and regulations administered by FDA.

Recent letters have added the additional ‘disclaimer’ – which is not unprecedented, but it isn’t a common one. That said, it was also in two letters made available this week. The CAPITALS are my insertion:

The specific violations noted in this letter and in the lnspectional Observations, Form FDA 483, issued at the close of the inspection MAY BE SYMPTOMATIC OF SERIOUS PROBLEMS IN YOUR FIRM’S MANUFACTURING AND QUALITY ASSURANCE SYSTEMS. You should investigate and determine the causes of the violations, and take prompt actions to correct the violations and to bring your products into compliance….

The new FDA focus on enforcement ties in with their attention to two key areas – the Quality and Manufacturing systems. It also points out the responsibility to take investigations seriously and make your CAPA system work:

“You should investigate and determine the causes of the violations, and take prompt actions to correct the violations and to bring your products into compliance.”

Many of you may observe that all of the above is quite basic and should go without saying, to use an old phrase. While I agree, the agency keeps saying it – and saying it more pointedly. The question should be therefore – is the industry listening? More specifically, since these letters are addressed to Senior Management, will there be additional efforts by FDA to question why quality activities are not carried through? Another letter posted this week (CDER product) includes this statement – the unsaid question is why is this happening. Again, the CAPITALS are my addition.

“Our inspection found your firm’s quality unit failed to adequately review batch records. The above major batch record deficiencies underscore the importance of appropriate quality unit oversight at YOUR firm……

YOU are responsible for investigating and determining the causes of the violations identified and for preventing their recurrence and the occurrence of other violations. It is YOUR responsibility to ensure your facility operates in compliance with all requirements of federal law and FDA regulations….”

Those of you who do the field level compliance work know who you are. The question is who has the authority to enable these efforts? And what steps are being taken to ensure the field level efforts are successful?

NOTE – Since these letters represent trends, the specific companies are not identified. 
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John English is a consultant to the life sciences industry.