Devine Guidance

Tick-Tock: 15-Days and the Clock is Ticking

By Dr. Christopher Joseph Devine
July 7, 2016


• Categories: 05-Quality/Regulatory, Devine Guidance

For those readers who reside in the United States, Dr. D hopes you and your families had a fabulous Fourth of July. For this week’s guidance, the doctor wants to expound on the importance of responding to Form 483 observations within the allotted 15-day time period. As the Chief Jailable Officer (CJO) and recipient of the warning letter mentioned in this week’s guidance quickly found out, violating the 15-day rule results in an extremely peeved FDA that will not review the delinquent response. In fact, the FDA will quickly move to the awarding of a not-so-prestigious warning letter as an appropriate reward for offending device establishments. You see my dear readers, all of the goodwill an establishment builds with the agency can be quickly extirpated (look-it-up) over something as simple as failing to respond to Form 483 observations within 15 days. Just ask any CJO that has had the misfortune of missing this agency rule. Enjoy!

Warning Letter – February 4, 2016

The warning letter referenced in this week’s guidance was fairly typical, with four observations that cite: (a) §820.75 – process validation, (b) §820.100 – CAPA, (c) §820.70(i) – validation of computer software, and (d) §820.184 – Device History Records. In fact, the Form 483 observations, as written, appear to be pretty innocuous. So what ticked off the FDA? The late response to Form 483 observations was clearly the deal breaker for this device establishment and the agency.

Warning Letter Excerpt

“We received responses from (name) Quality Manager, dated October 1, 2015, and October 27, 2015, concerning our investigator’s observations noted on the Form FDA 483 (FDA 483), List of lnspectional Observations, which was issued to your firm. Your firm’s response dated October 27, 2015, to FDA 483 was not reviewed because it was not received within fifteen business days of issuance of the FDA 483. This response will be evaluated along with any other written material provided in response to the violations cited in this Warning Letter.”

Compliance for Dummies

There really is not much to say about compliance in regards to responding to inspectional observations. Fifteen days is the acceptable threshold enforced by FDA. The best recommendation Dr. D can offer is to respond within the allotted window. Please note, it is incumbent upon all CJOs to clearly understand any and all inspectional observations noted prior to the investigator leaving your establishments. It is okay to disagree with an observation, but arguing at the end of an inspection is not the appropriate forum. A simple statement that you will provide additional evidence is all that is necessary. For all other observations, a simple commitment to correct the issue will suffice and should be annotated on the Form 483 at the end of the inspection. However, the doctor suggests working on all corrections ASAP!

Additionally, make sure the formal response to the Form 483 observation(s) is well-written and includes documented evidence that the compliance issue or issues have been thoroughly vetted, including documented evidence (e.g., new or revised procedure). Just stating that the violations will be corrected in the formal response will accelerate your establishment’s path to a warning letter. Failing to respond to the inspectional observations within 15 days and the path to a warning letter accelerates at the speed of sound—the sound of the tears from an offending establishment’s CJO cascading on to a desktop. Just to be on the safe side, make sure the response sent to FDA is sent overnight with a signature required. Just dropping a response letter into regular mail is tempting fate. You might as well poke a sleeping bear in the eye with a sharp stick.

Takeaways

For this week’s guidance there is just one takeaway: Tick-tock, tick-tock, tick-tock, the clock is ticking. Device establishments have 15 days to respond to a Form 483. Failure to respond within 15 days and the outcome is simple: A warning letter is awarded, and one does not have to be clairvoyant to see the outcome. In closing, thank you again for joining Dr. D, and the doctor hopes you find 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 2015). 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. (February 2016). Inspections, Compliance, Enforcement, and Criminal Investigations. Eolane Vailhauques. Accessed July 4, 2016. Retrieved from http://www.fda.gov/ICECI/EnforcementActions/WarningLetters/2016/ucm508652.htm