The identification and segregation of nonconforming product should be categorized as a mission-critical process within your quality system. Yes, it is a fundamental requirement of the Quality System Regulation (QSR. However, if an organization fails to control nonconforming product, it risks the ire of the agency during one of their friendly visits. Can you say Form 483 observation? Can you say warning letter? Can you say RECALL?

I know, there goes Dr. D. throwing around that nasty six-letter word again. But seriously folks, Dr. D wants to ensure the organizations, supported by my readers, are never on the receiving end of an enforcement action pursued by the FDA, when the agency heaps contumely on you for failing to comply with the requirements delineated within the QSR. Trust me when I say; “enforcement actions are never any fun.”

Warning letter violations
As depicted in this edition of DG, the extractions taken from FDA’s Website, violations of 820.90 are plentiful. One of the trends Dr. D has noted while performing research and collecting information for DG is that several companies have racked up multiple violations of the QSR, with the end result being a warning letter that is a small book. The doctor just does not understand how medical device manufacturers, regardless of size, continue to make the same mistakes.

Let’s not sugarcoat this device manufacturer’s compliance issues: Nineteen observations, as depicted in the second warning letter extraction, borders on absurd and is a compliance disaster. Regardless, the behavior exhibited by these manufacturers is the failure to comply with DG Rule # 6 – All procedures, work instructions, drawings, specifications, etc. must be written, well-documented, and controlled within a defined document control system. “Failure to establish and maintain procedures” continues to be a common theme.

Additionally, for these warning letter recipients, the concept of formal and documented investigations appears to be foreign. Folks, Dr. D will go on record as stating; “identifying a problem or nonconformance is the easy part, while correcting the nonconformance and ensuring a recurrence does not occur takes some significant work.” Can you say use your corrective and preventive action (CAPA) system? 

Warning Letter One (April 2010): Observation 3 of 5 – Failure to establish and maintain procedures that address the need to evaluate and document an investigation in order to control product that does not conform to specified requirements as required by 21 CFR § 820.90(a). Specifically, your written procedure for Control of Nonconforming Product (Quality System Procedure 8.3, dated March 22, 2004) does not require an evaluation of the need for a documented investigation for nonconforming products.

Warning Letter Two (April 2010):

Observation 8 of 19 – Failure to establish and maintain procedures that address the identification, documentation, evaluation, segregation, and disposition of nonconforming product, as required by 21 CFR 820.90(a). For example, there is no defined method of identifying, documenting and evaluating nonconforming product and any investigation associated with the nonconforming product. Specifically, email correspondence between the dates of June 29 and July 6, 2009, indicate the need to correct a problem with the data entry field on the waterload software version; however, no further documentation is available addressing this issue.

Quality System Regulation – 21 CFR, Part 820
QSR – Subpart I – Nonconforming Product Section 820.90 Nonconforming Product

(a) Control of nonconforming product. Each manufacturer shall establish and maintain procedures to control product that does not conform to specified requirements. The procedures shall address the identification, documentation, evaluation, segregation, and disposition of nonconforming product. The evaluation of nonconformance shall include a determination of the need for an investigation and notification of the persons or organizations responsible for the nonconformance. The evaluation and any investigation shall be documented.

(b) Nonconformity review and disposition.

(1) Each manufacturer shall establish and maintain procedures that define the responsibility for review and the authority for the disposition of nonconforming product. The procedures shall set forth the review and disposition process. Disposition of nonconforming product shall be documented. Documentation shall include the justification for use of nonconforming product and the signature of the individual(s) authorizing the use.

(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.

Nonconforming product
The effective handling of nonconforming product is essential for all device manufacturers. Identifying, removing, investigating, correcting, and verifying are salient steps that need to be completed. Trust Dr. D when I say, “the mishandling of nonconforming product can be costly, resulting in product withdraws (RECALLS), and inviting a surprise visit from FDA.”

A major failing I find with most systems created for managing nonconforming product is the lack of verification, or shall I say, a 360-degree approach to managing the process. As the doctor stated earlier, identification is only a small piece to the puzzle. The best guidance Dr. D can offer is to invest in developing an effective process for managing nonconforming product. The process should include (a) robust procedures; (b) a well-designed form; (c) a link to CAPA; (d) a clearly-defined process for disposition; (e) the creation of nonconforming-product tags; (f) a segregated storage area (restricted access); (g) instructions for rework; (h) supplier notification or supplier corrective action request (SCAR), if warranted; (i) a policy for returning nonconforming product to the supplier; (j) a Material Review Board (MRB) process; and last but not least, (k) a step for the verification of effectiveness.

Control of nonconforming product
Dr. D broken-record time: every QSR requirement commences with a procedure. As depicted in the warning letter section, one of the very first things you can expect from the agency, during a friendly visit, is a review of applicable procedures. Having no procedures quickly equates to Form 483 observations, and multiple Form 483 observations equates to a warning letter.

The QSR requires, at a minimum, that procedure(s) address identification, evaluation, segregation, and disposition. Wait a minute Dr. D: in the previous paragraph, you asked for significantly more data and control. While that’s correct, here’s the explanation. It is the doctor’s belief that teaching and preaching compliance is the goal of DG; however, some processes require more than just compliance to be effective. I think the handling of nonconforming product is one of those salient processes requiring more.

The need for an investigation, potentially root-cause analysis, and the notification of the appropriate organizations (internal and external) are required. If the nonconformance is determined to be external, a.k.a., supplier generated, a SCAR should be issued to prevent a recurrence of the nonconformance. Additionally, ensure all SCAR activity is closed with a verification of effectiveness step; otherwise, history will repeat itself. Furthermore, all of these activities shall be documented. Why – “because documented evidence of compliance is your best defense during a friendly visit from the agency.”

Nonconformity review and disposition
Since the procedure requirement has already been established, let’s focus on authority and disposition. For starters, you should never have manufacturing be the sole authority for providing disposition of nonconforming product. At a minimum manufacturing, purchasing, quality, supply chain, R & D, manufacturing engineering and quality engineering should have their say. Extended reviewers, employed as necessary, can be clinical or medical sciences, marketing, sales, and the cafeteria (just kidding).

Additionally, all dispositions require names, signatures and dates. Furthermore, Dr. D STRONGLY RECOMMENDS that use-as-is (UAI) never be used for Class 3 devices. A UAI disposition implies product does not meet specification and a conveyance is required to accept the product. In short, the nonconforming product now meets a different specification, probably wider. This equates to a design change. Now you can argue with the doctor until the cows come home, but you will never win this argument. My recommendation will always be to rework nonconforming product to print, scrap and remanufacture, or return the nonconforming product to the supplier. The risk is just too high. Finally, document the results. Why? Because documented evidence of compliance is your best defense during a friendly visit from the agency.

Rework of nonconforming product
Rework of nonconforming product is an area where I see device manufacturers often getting themselves into trouble. You already know Dr. D’s position on UAI. That said, reworking nonconforming product to established and approved specifications is a viable option. That said, device manufacturers should not exhibit reckless insouciance (look-it up time) about the rework process. As part of the rework process, the agency’s expectation is that the product be retested and/or reevaluated to achieve and ensure compliance to the product’s approved specification. If the current product specification is not approved or has been changed and not approved, your organization has other issues to deal with, which will quickly multiple when the agency visits. Remember design and process changes to Class 3 product will require an FDA review and approval. Can you say 30-day PMA Supplement?

Additionally, the reworked product needs to be assessed for potential long-term impact to product performance, a.k.a., product safety and efficacy. For example, let’s say a finished-device lot has been sterilized employing Ethylene Oxide (EO). While attempting to load the finished devices onto a truck for shipment to distribution, a forklift driver (and this is a true story) has managed to attack a pallet containing the product with the forklift. As part of the disposition, it has been determined the product will be inspected, repackaged, submitted to EO sterilized a second time, and released for distribution. If the finished devices were only validated for one sterilization cycle (1X), you now have a problem. That is why all aspects of the rework need to be evaluated. Furthermore, all rework activities shall be documented and placed into the Device History Record (DHR).

Finally, Dr. D recommends the DHR be maintained in a pristine condition as accuracy counts. Trust me, FDA will look at your DHRs and use the review as a stepping-off point for their investigation. Remember, the DHR contains the entire manufacturing history for each device or lot of finished devices. Finally, a complete and accurate DHR is extremely important; “because documented evidence of compliance is your best defense during a friendly visit from the agency.”

Effectively control nonconforming product
The key takeaways for this edition of DG are: (a) sticking to procedures, procedures, and more procedures, (b) understanding the importance and elements of effective control of nonconforming product, (c) refraining from the UAI disposition, (d) reworking to approved specifications, and (e) maintaining and updating accurate DHRs. If nonconforming product is not effectively controlled, market withdraws should be expected. If FDA shows up at your doorstep unannounced, due to a Class 1 or Class 2 RECALL, well that should not be a real surprise.

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, when I evaluate Subpart – J (Corrective and Preventive Action), specifically (820.100) – cheers from Dr. D. and best wishes for continued professional success.

References:

1. Code of Federal Regulation. (2009, April). Title 21 Part 820: Quality system regulation. Washington, D.C.: U. S. Government Printing Office.

2. Devine. C. (2009, July). Exploring the effectiveness of defensive-receiving inspection for medical device manufacturers: a mixed method study. Published doctoral dissertation.  Northcentral University. Prescott Valley, AZ. 

3. FDA – U.S. Food and Drug Administration Website. (2010). Warning letters. Retrieved August 19, 2010, from http://www.fda.gov/ICECI/EnforcementActions/WarningLetters/