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

One, Two, Three Strikes You’re Out…Or, Receive a Warning Letter

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

It is in the best interest of an offending establishment to be timely and complete in responding to Form 483 observations.

Similar to death and taxes, it is inevitable that many of the readers will end up working for a company that runs afoul of FDA and receives a warning letter. Although warning letters can literally cripple an establishment, while boosting the business fortunes of a competitor, they can actually be prevented with a well-planned and articulated response to Form 483 observations received during the agency’s friendly visit for a cup of coffee and an inspection. Seriously, many warning letters can actually be prevented by following two very simple rules: (a) respond to all Form 483 observations within 15-days; and (b) provide FDA with an intelligent response supported by documented evidence of compliance and/or a well-written correction plan, as appropriate. Otherwise, what happened to the device establishment mentioned in this week’s Devine Guidance (DG) could be in your establishment’s future. When responding to Form 483 observations, the best advice Dr. D can offer is to avoid needless circumlocution (look-it-up) that fails to adequately address the observation. Otherwise, that prized agency warning letter could be in your establishment’s future. Enjoy!

Warning Letter – September 9, 2015

As alluded to in the title, the target of this week’s DG struck out when it came to scripting acceptable Form 483 responses. Failing to have adequate procedures for design controls or CAPA are probably not warning letter worthy if an adequate response is provided to FDA. Failing to notify FDA when a recall occurs—that is probably going to end badly. The combination of bad procedures, bad Form 483 responses, and bad decisions—that is clearly a winning trifecta that will garner the attention of the agency. Folks, place your bets.

Observation One: “Failure to establish and maintain procedures to control the design of the device in order to ensure that specified requirements are met as required by 21 CFR 820.30(a).”

Strike One:“Your response to this observation is not adequate.”

Observation Two:“Failure to establish procedures for corrective and preventive action, as required by 21 CFR 820.100(a). Specifically, your procedures for corrective and preventative actions (CAPA) do not ensure adequate investigation of the cause of nonconformities relating to product; identify the action(s) needed to correct and prevent recurrence of nonconforming product; and ensure via verification or validation that the corrective and preventive action is effective and does not adversely affect the finished device as evidenced by the following examples noted upon review of CAPA #69.”

Strike Two:We have reviewed your responses to this observation, dated June 5, 2015 and June 30, 2015, and have concluded they are not adequate.”

Observation Three:“Failure to submit a written report of a correction or removal of a device initiated to reduce a risk to health posed by the device, or to remedy a violation of the Act caused by the device, which may present a risk to health, as required by 21 CFR 806.10. … Your firm failed to notify the FDA of the medical device correction or removal, and did not provide the information required by 21 CFR 806.10. Your firm’s actions have been reviewed by FDA and determined to meet the definition of a recall and should have been reported to the Agency.”

Strike Three: “We have reviewed your responses to this observation, dated June 5, 2015 and June 30, 2015, and have concluded they are not adequate. Your responses do not indicate you would report this medical device correction or removal, or a similar action, in the future. Your response does not include objective evidence to support corrections are proposed or have been made to correction and removal procedures to prevent this violation from recurring.”

Compliance for Dummies

Responding to Form 483 observations is not rocket science. Upon receipt of the Form 483 observations, the clock starts ticking…tick-tock, tick-tock, tick-tock, etc. An organization has 15 working days to respond to the FDA. The goal of the Form 483 response is to ensure the FDA is provided with a timely and complete response. When responding to FDA, some of the best advice Dr. D can offer consists of:

  • Providing a restatement of each Form 483 Observation in the response letter
  • Scripting the proposed corrective action or plan (including past, current and future states influenced by the observation are addressed)
  • Making reference to the specific CAPA number assigned by the establishment (please tell Dr. D that you promise to open a CAPA for each Form 483 observation)
  • Providing, if possible, an initial root cause or clearly state root cause is a salient element of your establishment’s CAPA process
  • Not forgetting to mention that verification of effectiveness will be pursued to ensure correction activities pursued are effective
  • Ensuring potential impact to products is considered as part of the response
  • Ensuring the potential impact to the quality system is considered as part of the response
  • Ensuring the targeted completion date for each CAPA is provided

Additionally, Dr. D would like to provide some advice that is always useful when interacting with the FDA. Please keep in mind that it will be in the best interest of the offending establishment to work quickly toward Form 483 observation remediation.

  1. Never, never, never, never, complain to the FDA, or publically state that the agency has singled out your establishment and is intentionally bullying it. The argument will never fly.
  2. Never fail to respond back to the agency, within the 15 days allotted or fail to meet committed dates made by your establishment in support of completing mitigation activities.
  3. Remember, the agency will verify that all objectionable conditions have been corrected during their next inspection. A repeat Form 483 observation will equate to a prized agency warning letter.
  4. Always provide the agency with sufficient detail and supporting documentation that accurately states the actions pursued in support of the corrections.
  5. If the corrections are going to take a significant amount of time, give the FDA a reasonable timetable for correcting all of the objectionable conditions. Ensure that status updates are routinely provided to the agency.
  6. Never downplay or minimize the seriousness of the Form 483 observations.


For those readers growing a little long in the tooth (like Dr. D), you probably remember the old Smokey the Bear commercials: “Only you can prevent forest fires!”  The doctor would like to borrow that saying, with a few minor revision: “Only you can prevent warning letters!” It’s kind of catchy. That being said, Dr. D will leave the readers with just one takeaway for this week’s guidance: The receipt of Form 483s during an agency inspection is a simple fact of life in the medical device world. However, how an establishment responds to the observation is the difference between quality and regulatory bliss versus quality and regulatory purgatory, under the guise of a warning letter. Please do not be that establishment that provides the FDA with unacceptable responses to Form 483 observations. Just like Smokey the bear, the FDA does have teeth and they are not afraid to use them. 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. (September 9, 2015). Inspections, Compliance, Enforcement, and Criminal Investigations, CMP Industries, Inc.. Accessed September 9, 2015. Retrieved from http://www.fda.gov/ICECI/EnforcementActions/WarningLetters/2015/ucm462058.htm

About The Author

Dr. Christopher Joseph Devine, President, Devine Guidance International