Dr. D has stated on more than one occasion, there is no rhyme or reason when it comes to making a surefire link between inspectional observations and a warning letter. For example, in 2015, Theranos received 14 Form 483 Observations (two facilities combined) and received no warning letter; however, Medtronic (Puerto Rico) received two observations and a warning letter in August of this year. Go figure. Regardless of what is perceived as being fair and equitable, Dr. D was not there so the doctor will just leave it at the numbers and let the readers decide. The underlying story in this week’s guidance is not the issuance of a warning letter but a specific observation pertaining to device history records (DHRs) and the inclusion of rework information into the DHR. Rest-assured people, during most agency inspections the investigator(s) will eventually find their way into your DHRs or rework activities. After all, the DHR is nothing more than documented evidence that finished devices were manufactured in accordance with their device master record (DMR). Having had the pleasure of sitting through many agency inspections, the doctor always cringes when it comes to the review of DHRs and all of the potential pitfalls associated with not compiling accurate DHRs. In fact, this problem becomes greatly exacerbated when device establishments rely heavily on critical subcontractor and crucial suppliers for the manufacture of finished devices. Dr. D cannot think of one chief jailable officer (CJO) who wants to sit across from an investigator from the FDA, during an inspection, and attempt to defend missing or incomplete DHRs. The most vocal of CJOs could attempt to launch rodomontade (look-it-up) at the FDA investigator in attempt to deflect a potential Form 483 Observation; however, the likelihood of success would be slim. Enjoy!
Warning Letter – August 23, 2018
As mentioned in the opening to this week’s guidance, the warning letter reviewed this week contained two relatively innocuous observations. In fact, premised on the FDA’s responses to each observation, it appeared the agency was happy with Medtronic’s initial mitigation plans, Frankly, Dr. D is somewhat surprised that this inspection resulted in a warning letter, but as previously stated, the doctor was not there. Dr. D is going to climb out onto that proverbial limb and provide some conjecture and wonder if it was because the devices being manufactured at this facility were Class III implantable devices.
Warning Letter Excerpt(s)
Observation Two (2) – “Failure to document (b)(4) activities in the device history record (DHR) as required by 21 CFR 820.90(b)(2). Specifically, (b)(4) on implantable cardiac defibrillators (ICDs) was not documented in device history records.”
“We reviewed your firm’s responses to the FDA 483 and acknowledge your commitment to: (a) (b)(4) process, (b) update product identification and traceability procedures to clarity that (b)(4) must be documented, (c) update your training of new hires and manufacturing personnel, (d) assess manufacturing areas to identify whether similar conduct is occurring elsewhere, and (e) establish more robust equipment and/or procedure controls on ICD equipment used in manufacturing to help prevent the occurrence of undocumented (b)(4). Your responses appear to be adequate; however, some of your firm’s actions are still in progress, and a follow-up inspection by FDA will be necessary to verify compliance.”
21 CFR, Part 820.90(b)(2) – Nonconforming Product
“(2) Each manufacturer shall establish and maintain procedures for rework, to include retesting and reevaluation of the nonconforming product after rework, to ensure that the product meets its current approved specifications. Rework and reevaluation activities, including a determination of any adverse effect from the rework upon the product, shall be documented in the DHR.”
Compliance for Dummies
There is no question rework continues to grow in importance not only with device manufacturers attempting to squeeze every dollar out of the product realization process by reducing scrap. Conversely, the FDA needs to ensure that rework activities are not impacting product safety and efficacy issues or influencing long-term product reliability. That being said, it is incumbent upon device manufacturers and required by regulation, that procedures for rework shall be established (define, document and implement). Additionally, reworked product shall be tested and or/inspected to ensure that reworked devices still meet their approved specifications. Furthermore, rework, retest, re-inspection, and any other applicable “re” activities deemed to be appropriate, need to be captured in the DHR. Finally, any potential adverse influence rework may have on a finished device needs to also be captured in the DHR.
Why is the FDA concerned about the rework of medical devices? Rework implies that a nonconforming state occurred at some point in time. Rework is the correction of the nonconformity or some other activity that brings a device back into compliance with its specification(s). For example, a finished device may have exhibited an electrical failure during final test. A component was replaced, and the device passed retest. The FDA wants the fact that the device was reworked/retested documented; and it wants to know if there is any potential for a future adverse event (e.g., pre-mature device failure in the future). It really does not get any simpler than that folks.
For this week’s guidance, the doctor will leave the readers with three takeaways. One: The DHR is nothing more than documented evidence that a device was manufactured in accordance with the DMR. Two: All rework activities, regardless of how benign they appear to be, shall be documented in the DHR. Three: Any potential for rework having an adverse influence on the finished device shall also be documented in the DHR. In closing, thank you again for joining Dr. D, and I hope you found value (and some humor) 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 2017). 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. (August 2018). Inspections, Compliance, Enforcement, and Criminal Investigations. Medtronic Puerto Rico Operations Co. Accessed October 1, 2018. Retrieved from https://www.fda.gov/ICECI/EnforcementActions/WarningLetters/ucm619206.htm