There is nothing like a well-constructed device history record (DHR) that reflects finished devices have been manufactured in accordance with their device master record (DMR) to warm the hearts of a chief jailable officer (CJO) during an agency inspection. Rest-assured, our dear friends from FDA, when they arrive in the lobby for that friendly cup of coffee and an inspection, will take a peek into an establishment’s DHRs. Failure to have DHRs that demonstrate compliance with the DMR leads to bad things happening during an inspection. The CJO does not need to be clairvoyant or possess a functioning crystal ball to see into the future to witness the FDA investigator tapping on those keys as the Form 483 observations come to life. In fact, an establishment that fails to demonstrate compliance during a review of DHRs faces an even more perilous fate than being on the receiving end of a Form 483 observation. Can you say adulterated product? Can you market withdraw? Seriously, failure to prove a finished device has been manufactured in accordance with its DMR and the big question becomes, “Why is this product on the market?” No amount of bloviating (look-it-up) by a CJO is going to be able to talk the FDA out of writing Form 483 observations when DHRs are problematic. Enjoy!

Warning Letter – February 27, 2018

The warning letter recipient mentioned in this week’s guidance was on the receiving end of a six-Form 483 observations warning letter. Each of the observations began with the agency’s typical “failure to establish” comment. Remember, “establish” is a key ingredient needed to understand the underlying text associated need for complying with that element of the quality system regulation. According to FDA, “establish means define, document (in writing or electronically), and implement.” Failure to establish is almost always going to result in a Form 483 observation. These types of lapses in a QMS can be prevented with well-written procedures that are followed, or should be quickly remedied once a Form 483 observation has been issued. However, when finished devices come into question due to issues with the DHR, all bets are off.

Warning Letter Excerpt

Observation Five (5) – “Your firm failed to establish procedures to ensure that device history records (DHR) for each batch, lot, or unit are maintained to demonstrate that the device is manufactured in accordance with the device master record (DMR), as required by 21 CFR 820.184.”

“a. Your firm’s DHR for lot 700 of your (redacted name) device, does not include the quantity of products released for distribution, the acceptance records showing the product was made in compliance with the DMR, or the primary identification label.”

“b. Your firm’s DHR for lot 17-03-7105 of your (redacted name) devices does not include the quantity of products released for distribution, the acceptance records showing the product was made in compliance with the DMR, or the primary identification label.”

“c. Your firm’s DHR for lot 17-03-7106 of your (redacted name) devices does not include the quantity of products released for distribution, the acceptance records showing the product was made in compliance with the DMR, or the primary identification label.”

“We have reviewed your response and determined the response is inadequate. Although your response states you will implement your DHR procedure SOP 018; your response does not include any retrospective review of your manufactured product to determine if additional lots’ DHRs were deficient. Additionally, your response does not address how your firm will remedy the deficient DHRs identified on the FDA 483.”

21 CFR, Part 820.184 – Device History Record (DHR)

“Each manufacturer shall maintain device history records (DHR’s). Each manufacturer shall establish and maintain procedures to ensure that DHR’s for each batch, lot, or unit are maintained to demonstrate that the device is manufactured in accordance with the DMR and the requirements of this part. The DHR shall include, or refer to the location of, the following information:

(a) The dates of manufacture;
(b) The quantity manufactured;
(c) The quantity released for distribution;
(d) The acceptance records which demonstrate the device is manufactured in accordance with the DMR;
(e) The primary identification label and labeling used for each production unit; and
(f) Any unique device identifier (UDI) or universal-product code (UPC), and any other device identification(s) and control number(s) used.”

Compliance for Dummies

If you take anything away from this week’s guidance, please understand that the DMR is nothing more than the recipe needed to successfully manufacture a finished medical device that is safe and effective in its intended use. The DHR is nothing more than a compilation of records that contains the documented evidence that a finished medical device was manufactured in accordance with its DMR. Simply stated, no DMR equates to no DHR; and no DHR equates to no demonstrated evidence of compliance. The DMR and DHR should be considered and treated as a married pair.
So what does the agency inspect to see in the DHR? For device establishments, the DHR should contain:

• The production traveler (router) that reflects all of the manufacturing steps including: (a) the total number of devices accepted and rejected, (b) dates the activities were performed, and (c) the names of the individuals performing the activities
• The results of inspection and test activities, including the records of inspection and test activities or a pointer as to where these records can be found
• The material BOMs (as built configuration)
• Number of finished devices released to commercialization, including the date released and the individual tasked with authorizing the actual release
• A copy of the labeling (product label and/or IFU) used for each lot or unit release for distribution
• The unique device identifier (UDI), serial number or lot/batch number that was used to establish product identification and traceability

If an establishment has a well-written procedure that captures the aforementioned bullet points and actually adheres with their written procedure(s), the CJO will never have to stress over sitting across from the FDA during an inspection. The visits from the agency will continue to pleasant.

Takeaways

For this week’s brief guidance, Dr. D will leave the readers with just one takeaway: The DHR contains the documented evidence that a finished medical device was manufactured in accordance with its DMR. Folks, this is not rocket science. Conversely, no DMR equates to no manufacturing being possible. Why? Well if you must ask, it is not possible to demonstrate compliance with the DMR if a DMR has not been constructed. What is being used for the blueprint for manufacturing? No DHR, no DMR, no problem; the FDA will probably ask the offending establishment to stop entering their adulterated product into commerce. 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.

References

1. Code of Federal Regulation. (April 2017). 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 2018). Inspections, Compliance, Enforcement, and Criminal Investigations. Laser Dental Innovations. Access April 21 2018. Retrieved from https://www.fda.gov/ICECI/EnforcementActions/WarningLetters/ucm599613.htm