Dr. Christopher Joseph Devine, President, Devine Guidance International
Devine Guidance

Getting Fat on Form 483 Observations

By Dr. Christopher Joseph Devine
Dr. Christopher Joseph Devine, President, Devine Guidance International

FDA appreciates nothing more than documented evidence of compliance.

For those readers in the United States who have decided to read Dr. D’s column this week, the doctor is going to assume you have already filed your tax returns for 2015. Failing to file a tax return and tempting fate with the Internal Revenue Service (IRS), is not unlike a Chief Jailable Officer (CJO) tempting fate with the FDA by failing to ensure a device establishment’s Quality Management System (QMS) complies with the Quality System Regulation (QSR). How about that, Dr D. has managed to use five acronyms in the same sentence: IRS, CJO, FDA, QMS, and QSR? Fabulous! On a serious note, Dr. D came across a recently issued warning letter awarded to an establishment named Miami Fat Supply—henceforth, this week’s title. It seems that in a very short two-day inspection the FDA investigator was able to quickly script eight Form 483 observations. Please keep in mind, there is no universal antidote, a.k.a., mithridate (look-it-up) for bad quality practices that result in the winning of a prized agency warning letter. However, taking the time to script a few well-written procedures can result in the CJO not having to swallow that bitter poison pill. Enjoy!

Warning Letter March 17, 2016

As mentioned in the introduction, this week’s offending establishment managed to rack up eight Form 483 observations during a brief two-day inspection. Additionally, the warning letter mentions a few phrases that never bode well with FDA such as: (a) “failed or refused to furnish material or information;” (b) “your firm has not received premarket clearance or approval;” (c) “misbranded;” and the infamous (d) “adulterated.” In any event, the warning letter makes for a good read for inexperienced device establishments and CJOs not wanting to run afoul of the agency. Poking a sleeping bear in the eye, with a sharp stick, just might result in a better outcome than a ticked off FDA. Run baby run!

Warning Letter Excerpt

Observation One (8) –  “Failure to establish procedures for quality audits and conduct such audits to assure that the quality system is in compliance with the established quality system requirements and to determine the effectiveness of the quality system, as required by 21 CFR 820.22. For example, your firm’s representative stated to the FDA investigator that your firm has not established and does not maintain procedures for the conduct of quality audits at defined intervals. Your firm has marketed the Red Head as of October 2011, the Read Head 2 as of January 2013, and the Jordy Connection System as of October 2013, but has not conducted internal quality audits.”

21 CFR, Part 820.22 – Quality Audit

“Each manufacturer shall establish procedures for quality audits and conduct such audits to assure that the quality system is in compliance with the established quality system requirements and to determine the effectiveness of the quality system. Quality audits shall be conducted by individuals who do not have direct responsibility for the matters being audited. Corrective action(s), including a reaudit of deficient matters, shall be taken when necessary. A report of the results of each quality audit, and reaudit(s) where taken, shall be made and such reports shall be reviewed by management having responsibility for the matters audited. The dates and results of quality audits and reaudits shall be documented.”

Compliance for Dummies

The doctor would like to start off the compliance piece by stating a simple but very important fact. In accordance with §820.180(c), device establishments do not have to share the content of internal audits with the FDA, only evidence that they have been performed in accordance with the QSR. The CJO can provide FDA with a certified statement of compliance. Dr. D always recommends providing a copy of an audit plan, agenda and sign-in sheet. Remember, there is nothing the FDA and CJOs appreciate more than documented evidence of compliance.

As for complying with the §820.22, there are simple steps that each device establishment can pursue to ensure that the audit program is always in compliance with multiple regulatory environments.

  1. Create and release an annual audit schedule. It really does help to have a well-written cross-reference matrix that reflects all of the elements associated with 21 CFR, Parts 801, 803, 806, and 820 requirements; ISO 13485 requirements; and other quality, regulatory, and statutory  requirements as appropriate (i.e., EN ISO 14971:2012; SOR/98-282; 93/42/EEC, Ministerial Ordinance 169, MEDDEV 2.12-1; etc.).
  2. Remember, there are no certification requirements for auditors; however, training internal auditors to meet ISO 19011 requirements is always a good thing. It is also important to ensure internal auditors are knowledgeable about the quality, regulatory, and statutory requirements, and the processes they are tasked with auditing.
  3. As with all quality processes, a well-written procedure a fundamental requirement. For audits, the procedure should have the following elements:
    • Audit plan (remember, dates are important)
    • Audit agenda
    • Requirements for opening and closing meetings
    • A requirement to ensure individuals cannot audit their own functional areas of responsibility
    • A sign-in sheet for meetings and interviews
    • An audit checklist
    • An audit report and a requirement for management to actually read and review the reports
    • A link to CAPA should non-conformances be noted
    • A requirement for re-auditing problem areas
    • An extension clause (sometimes business needs trump quality, but hopefully not too often)
    • A link to management review (results should find their way into management review)


For this week’s guidance, the doctor will leave the readers with three takeaways. One: Audits (when performed with sufficient rigor) are excellent tools for identifying problem areas within an establishment’s QMS. Two: If audits never result in CAPA being pursued, then why bother auditing. Even the most perfect QMS’s will occasionally have a hiccup courtesy of Mr. Murphy and human nature.  Three: Please do not forget to file your taxes by Monday, 18 April (courtesy of Emancipation Day, celebrated on Friday, April 15 this year). 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.


  1. Code of Federal Regulation. (2015, April). Title 21 Part 820: Quality system regulation. Washington, D.C.: U.S. Government Printing Office.
  2. Devine, C. (2011). Devine guidance for complying with the FDA’s quality system   regulation – 21 CFR, Part 820. Charleston, SC: Amazon.
  3. Devine, C. (2013). Devine guidance for managing key attributes of a FDA-compliant quality management system – 21 CFR, Part 820 Compliance. Charleston, SC: Amazon.
  4. FDA. (March 17, 2016). Inspections, Compliance, Enforcement, and Criminal Investigations. Miami Fat Supply, Inc. Accessed April 13, 2016. Retrieved from http://www.fda.gov/ICECI/EnforcementActions/WarningLetters/2016/ucm495019.htm

About The Author

Dr. Christopher Joseph Devine, President, Devine Guidance International