Compliance for Dummies

Dr. D has always taken a before-state (historic), current-state, and future-state (post-correction) approach when responding to a Form 483 observation. What in the heck does that mean? For example (reference this week’s warning letter excerpt), if an establishment does not have procedures for acceptance activities, once the procedures have been established (defined, documented and implemented), a decision must be made on what to do with previously accepted product. Most establishments will bite the proverbial bullet and absorb the unanticipated costs associated with the re-inspection and/or re-test of previously accepted product. In the establishment’s response to FDA, the response should contain wording that clearly defines the activities being pursued to mitigate the inspectional observation such as:

• Scripting a procedure
• Performing re-inspection and/or re-test of previously accepted product
• Steps to be taken if previously accepted product is found to not be in compliance with its product specification, such as rework or a potential market withdraw (Recall, that nasty six-letter word)
• A thorough review of the Quality Management System (QMS) to verify if additional procedures need to be written
• Steps to be taken to preclude any recurrence of the same observation(s) in the future

Additionally, the agency loves to see documented evidence of compliance. In God We Trust, but all others bring data (thank you Dr. Deming). If a new procedure has been established in support of correcting a compliance deficiency, provide a released copy of the document to FDA. Trust the doctor when I say, the FDA loves to read procedures, you write it and the agency will read it.

Furthermore, if inspection and test activities are being pursued, provide the results of this additional testing as part of the response. Now granted, the FDA will probably not ask for all previously accepted products to be 100% tested, retested, inspected or re-inspected; however, the agency will expect some level of due diligence pursued. If a sampling approach is pursued, the FDA will expect to see a valid and cohesive sample-size rationale for the sample size selected. If the sample size is n=1, the CJO will definitely have some serious explaining to do.

Finally, responding to Form 483 observations is really somewhat of a unique art form. For example, the following elements should be included in the response:

• A regurgitation of the initial observation
• Containment activities pursued
• Impact to finished medical devices previously entered into commerce
• Impact to the QMS
• Steps taken to correct the compliance issue
• Verification of Effectiveness (VOE) of mitigation activities implemented
• Steps take to preclude a recurrence of the compliance issue
• Documented evidence for the previously mentioned bulleted points being executed

Now this may seem like a whole bunch of work for responding to a Form 483 observation, but trust Dr. D when I say that this truly is a pay-me-now versus pay-me-later scenario. The doctor has experienced, firsthand, the regulatory and ultimately fiscal pain associated with mitigating a prized agency warning letter. Believe it or not, it is so much easier to remain in compliance and the good graces of FDA versus having to navigate the tumultuous regulatory waters of a warning letter. Before the doctor forgets, make sure the response to any and all Form 483 observations finds its way into the hands of FDA within 15 days. Why? Can you say warning letter?

Takeaways

For this week’s guidance, the doctor will leave the readers with four takeaways. One: Each time you come across the term establish in the Quality System Regulation (21 CFR, Part 820), that is code for writing a procedure. There is no time like the present to start writing. Two: When responding to a Form 483 observation, always, let the good doctor repeat always, provide documented evidence of correction. Three: Ensure that previous, current and future-state scenarios are addressed. Unfortunately, sometimes a market withdraw may be the flavor of the day if the results of product re-testing and re-inspection proves to be problematic. Four: Make sure the FDA has the response within 15 days. If not, the failure to respond to Form 483 observations will quickly escalate to a warning letter. In closing, thank you again for joining Dr. D, and I hope you found value in the guidance provided. Until the next installment of DG, cheers from Dr. D., and best wishes for continued professional success.

References

1. Code of Federal Regulation. (April 2016). Title 21 Part 820: Quality system regulation. Washington, D.C.: U.S. Government Printing Office.
2. Code of Federal Regulation. (April 2016). Title 21 Part 803: Medical device reporting. Washington, D.C.: U.S. Government Printing Office.
3. Devine, C. (2011). Devine guidance for complying with the FDA’s quality system   regulation –21 CFR, Part 820. Charleston, SC: Amazon.
4. Devine, C. (2013). Devine guidance for managing key attributes of a FDA-compliant quality management system – 21 CFR, Part 820 Compliance. Charleston, SC: Amazon.
5. FDA. (August 2016). Inspections, Compliance, Enforcement, and Criminal Investigations. A.R.C.O.S., Srl. Accessed January 22, 2017. Retrieved from http://www.fda.gov/ICECI/EnforcementActions/WarningLetters/2016/ucm515195.htm