The quality director’s dog ate the book containing all of the SOPs. Our Chief Jailable Officer (CJO) recently quit. Our regulatory affairs manager is fresh out of college and has no practical experience. Seriously folks, all of the previous comments are plausible excuses (maybe not the dog); however, there are no excuses in business. This is especially true in the highly-regulated medical device industry. Excuses typically lead to Form 483 observations during FDA inspections. In fact, repeat Form 483 observations will equate to an instant warning letter. When the Form 483 observation is premised on a quality concern such as finished device acceptance, you can take the proverbial warning letter to the bank. For the repeat Form 483 observations, there is no doubt the FDA will heap contumely on the CJO for failing to correct previously identified observations. Ouch, ouch, and triple ouch. Enjoy!
Warning Letter – 12 June 2015
A few weeks ago, the subject of this week’s Devine Guidance was chastised for its calibration program, or lack thereof. While traveling on business last week, Dr. D reread the warning letter and noticed that two of the seven observations were repeat violations from the offending establishment’s previous inspection (in 2010). Folks, it is bad enough to have just one repeat nonconformance. Two is just raising that big red flag high into the sky, or at least into the rafters, for the investigator. Additionally (as mentioned earlier), one of the repeat observations was for finished device acceptance. When an investigator shows up for that cup of coffee and inspection and finds repeat violations, then bad things are going to happen, and quickly. When the response to Form 483 observations is deemed to be inadequate, then really bad things are about to happen. Can you say warning letter? I knew you could (thank you. Mr. Rogers).
Observation Three (3). “Your firm failed to adequately establish procedures for finished device acceptance, as required by 21 CFR 820.80(d). Specifically, review of Device History Record (DHR) for medical device #AG7178 (filter) Lot (b)(4) found only (b)(4) medical device product quality inspections conducted, although such device inspections are required to be conducted according to the sampling plan dictated by Checklist 7.6.14 in the Device History Record (DHR). The Checklist’s requirements call for an AQL sampling approach, AQL level (b)(4) for assembled devices. There is no documented justification for the reduced AQL level (b)(4). Further, there is no documentation that even this reduced AQL sampling is being performed.
Your firm’s response to this observation as captured in CAPA 15015 is inadequate because again your root cause is negligence on the employees’ part to fail to follow the established sampling plan and the established quality system, although your response does acknowledge that your Quality Procedure QP8.4-2 is not adequately written. Your response fails to address the lack of effective management oversight. Your response again states there is no impact on the finished product. With inadequate process validation (see 2. above), adequate inspection and testing of finished product is even more important.
Your response states that Quality Procedure QP8.4-2 will be updated to truly reflect current practices. Your current practices are inadequate and are the basis for the observation noted on the FDA 483 issued to your firm on 4/13/2015.
Again, your designation of CAP A 15015 as “minor” appears inappropriate for inadequate finished device acceptance procedures.”
This is a repeat observation from 2010.
21 CFR, Part 820.80 Receiving, In-Process, and Finished Device Acceptance
(d) Final Acceptance Activities. Each manufacturer shall establish and maintain procedures for finished device acceptance to ensure that each production run, lot, or batch of finished devices meets acceptance criteria. Finished devices shall be held in quarantine or otherwise adequately controlled until released. Finished devices shall not be released for distribution until:
- The activities required in the DMR are completed;
- The associated data and documentation is reviewed;
- The release is authorized by the signature of a designated individual(s); and
- The authorization is dated.
Compliance for Dummies
As stated in the warning letter, a lack of adequate product acceptance coupled with no process validation and employees failing to follow procedures, is a management oversight issue. The FDA quickly connected the dots and placed fault where it belonged, with management. Folks, meeting the final acceptance activities depicted within Part 820 are really some of the least burdensome requirements to meet. However, if a Device Master Record (DMR) has never been created, then meeting the requirements delineated within the DMR is going to be problematic. Do you think? Seriously, The DMR is nothing more than the recipe needed to manufacture a medical device that is safe and effective in its intended use. The Device History Record (DHR) is the compiled documented evidence supporting acceptance. The DMR and the DHR are two of the most salient and basic requirements anyone working in the device industry needs to comprehend.
Additionally, there has to be an established procedure(s) for finished device acceptance. Why? If you have to ask, well no comment from the doctor will be nice. Seriously, it is because the Quality System Regulation (QSR) requires it. Furthermore, the DHR needs to be reviewed for compliance with DMR requirements. This is especially true when no final device testing or inspection is being performed.
Finally, the release of finished devices into commerce (assuming clearance or approval has been obtained from FDA) must be authorized by a qualified individual and not the janitor (no offense to the janitorial staff). The signature must be accompanied by a release date. Now Dr. D is a quality purist and expects to see a qualified member of the quality organization releasing finished medical devices. The doctor always grows concerned during audits when he sees manufacturing releasing finished devices. If the DHR has several discrepancy reports and evidence of multiple reworks, the alarms sound and the red flag is raised. Now for those of you who fail to place enough emphasis on the DHR, the doctor had the pleasure of sitting through an inspection where the FDA investigator pulled DHRs for review from a 12-month period of time and commenced to review hundreds of DHRs. It does happen, and it could happen to your establishment during the next friendly visit from the agency.
For this week’s guidance, the doctor will leave just two takeaways.
- Please do not be that establishment with repeat Form 483 observations.
- Please do not be that establishment that provides an inadequate response to a Form 483 observation.
Nothing good will come from this non-compliant behavior. Always keep in mind Dr. D’s favorite quote; “There is no such thing as minimum compliance, there is no such thing as maximum compliance, there is only compliance.”
In closing, thank you again for joining Dr. D; and I hope you find value in the guidance provided. Until the next installment of DG, cheers from Dr. D. and best wishes for continued professional success.
- Code of Federal Regulation. (April 2014) Title 21 Part 820: Quality system regulation. Washington, D.C.: U.S. Government Printing Office.
- Devine, C. (2011). Devine guidance for complying with the FDA’s quality system regulation –21 CFR, Part 820. Charleston, SC: Amazon.
- Devine, C. (2013). Devine guidance for managing key attributes of a FDA-compliant quality management system – 21 CFR, Part 820 Compliance. Charleston, SC: Amazon.
- FDA (May 2015). Inspections, Compliance, Enforcement, and Criminal Investigations. AG Industries, Warning Letter. Accessed June 23, 2015. Retrieved from http://www.fda.gov/ICECI/EnforcementActions/WarningLetters/2015/ucm451494.htm