The CSO Diary
NO, part 211 are Code of Federal Regulations (CFR) and are general and permanent rules to administer legal minimal requirements to comply with lawful requirements and avoid a federal charge of a prohibited act. A general assumption that any section of 21 CFR covers all current good manufacturing practices is wrong. As mentioned in previous commentary, the same would apply to the concept that any legal notification such as a Notice of Observations and/or Warning Letter/Untitled Letter etc. issued by the FDA, encompasses all deviations from cGMPs during an inspection. A good practice in manufacturing may be defined by the firm to meet the minimal legal burden. A good practice may also exceed the regulation not mentioned in any CFR section. Finally, the concept of “all cGMP norms” does not exist legally or in practicality since it is a constant evolving improvement process without an absolute marker.
Regular street cops operate under the general guidance of “the necessary force to subdue a suspect.” While the industries regulated by the FDA would appear to be more sophisticated than the usual street suspect, the concept of consumer protection from an industry regulated by the FDA is basically the same. Whatever force (legal/regulatory action) is necessary to keep the noncompliant product from reaching the consumer. One of the main and principle differences in my example of the comparison of a street suspect is that the FDA’s actions are two-fold, it proceeds to “Arrest in REM” the non-compliant product and at times charges those responsible for introducing it in commerce.
While the concept of a “Consent Decree” sounds powerful regulatory wise, it is basically FDA checking the firm’s specific court-ordered compliance over time. There are some negative issues with this process. The process of a Consent Decree is resource intensive for both the FDA and the firm. In addition, the process of Consent Decree is necessary to keep the firm from additional criminal charges if they do not comply. The principle behind the Consent Decree is that hopefully by “holding their hand” to assure that they do it correctly long after the Consent Decree is done, the firm will continue to do it correctly. The Consent Decree basically takes precious resources away from inspecting other firms that might be operating in a similar noncompliant manner. The fine process is less resource intensive for FDA field staff, but it does little for a firm that has the resources to meet them and does not improve the controls. I believe that in both situations, Consent Decree and/or fines, the FDA strives to establish a path to the courts to follow-up with criminal proceedings, removing the product permanently and prosecuting the responsible, if the firm does not ultimately comply. The answer is both consent decrees and fines are equally powerful if they protect the consumer. A combination of both is usually the best.
The use of affidavits by FDA Inspectors and Investigators is part of the investigation, inspection and sample collection process. It is part of the basic training for FDA field staff. Affidavits serve several basic key functions for FDA staff. They are a way of condensing the story of establishing Jurisdiction, interstate commerce, violation and responsibility (JIVR). These are all necessary components of developing a solid evidence foundation in the event further regulatory action is contemplated by the agency. Most firms will instruct their staff not to sign one. At this point, the FDA usually reads the affidavit to the firm representative and will ask for acknowledgement of it being true. The answer is recorded usually in an FDA diary carried by the FDA investigator. This is done in the event the FDA investigator has to testify in a legal proceeding of the action later. Ironically most affidavits are written by the FDA investigator from the explanation given to him about JVIR and later ask the firm’s representative to read it and sign. They have limited legal use in actual court proceeding without direct evidence and testimony, but do tell a highly condense story of the FDA regulated product and its shipment by those responsible and knowledgeable on the process and at the same time keep an FDA inspector/investigator trainee on top of the evidence he has to collect. They are also helpful in documenting events to support testimony of the FDA officer in title 18 charges of providing false information in regulatory cases that develop into criminal cases. All in all, different district management reminds staff to tighten up the writing of affidavits from time to time.
I'm looking for objective evidence of 483 observations citing companies for having a lengthy open deviation going against the SOP. Does anyone have any recommendations regarding this?
First the obvious, it is difficult to claim that “one answer fits all,” so this answer is based on generalities. In the eyes of ORA/CDRH and more importantly compliance, they will support or not support an observation for regulatory action based on risk. An “open deviation” that keeps showing up in post-inspection might continue to show up in post-inspections if the risk is negligible or low. It is all about RISK and the exposure to the numbers. Reasonable time to correct the deviation has always been a staple in the regulatory buffet, but when the risk is high, the clock starts when the observation was made and management warned. This might be expressed verbally and in the 483 during the exit discussion with a possible call from compliance to account for current production and production already impacted by the deviation. In addition, the agency takes into consideration that an observation of deviation against an SOP and its impact on the firm’s quality system. In summary, “lengthy” if not specifically quantified in the firm’s SOPs will definitely be subjected to FDA’s definition of quantified and qualified using risk approach and most likely not to the benefit of the firm. My recommendation is to document risk, supported by solid investigation into why you arrived at that conclusion and that support you to buy time.