In this week’s edition of Devine Guidance (DG), the doctor will provide guidance for 21 CFR, Part 820 – Subpart – H, Acceptance Activities, and specifically (820.86), Acceptance Status. As Dr. D stated in the previous edition of DG, I did not forget acceptance status, I intentionally moved the topic to this week because I was enjoying a long weekend on the east coast; and the subject matter is relatively straight-forward from a discussion standpoint. That said, I decided to employ my right of predilection for enjoying some badly needed down time, and as a result, this article will be brief. Especially when compared to previous articles of DG, which exhibit the doctor’s propensity toward being longwinded.

Warning letter violation
From an enforcement vantage point, Dr. D. reviewed a few hundred warning letters and could not find a specific violation for 820.86. However, violations of 820.80 continue to be frequently cited by the agency. As my readers are keenly aware, the doctor is very big on procedures and the application of DG Rule # 6 – All procedures, work instructions, drawings, specifications, etc., must be written, well-documented, and controlled within a defined document control system.

This week’s warning letter extraction captures another device manufacturer that has failed to employ procedures capable of supporting compliance to the QSR; specifically failure of finished-device procedures to make sure acceptance criteria are adequately defined, while ensuring finished device acceptance is achieved. The lack of an adequate procedure automatically qualifies as a Dr. D no-no. Repeat after me, three-times, while clicking your heels together: ‘Procedures are a device manufacturer’s best friend, procedures are a device manufacturer’s best friend, procedures are a device manufacturer’s best friend. Yes, I stole the concept from The Wizard of Oz. Just think of FDA as the almighty and powerful Oz; however, if you received a warning letter, Dr. D thinks the Wicked Witch of the West might be more appropriate. Quick you had better hide Toto too (code name for your Chief Jailable Officer).

Warning letter one (August 2010): Observation 2 of 3 – Failure of your finished device acceptance procedures to ensure that each production run, lot or batch of finished devices meets acceptance criteria, as required by 21 CFR § 820.80(d).
Specifically, your “ELISA MATERIAL SPECIFICATION” procedures allow for the averaging of out-of-specification values and/or allow the removal of the out-of-specification value (OOS) for one replicate of the set if the “CV of the triplicates is > 10%” during finished device testing. A total of 17 of the 30 Phenylalanine Kits’ finished device testing records reviewed by the FDA investigator had one of the three values as OOS. Some of these OOS values were outside three standard deviations. Your firm does not conduct a failure investigation to determine the cause of these OOS results, nor is there a written justification based on a statistical rationale for acceptance of the OOS results.

Additionally, when your firm establishes values for your calibrators, which are used to create a standard curve, you routinely remove data points without documenting and justifying the rationale for removing these values. For example, in the last 2 years, you have manufactured two lots of these calibrators. One lot had 11 data points removed and the other two data points removed from the data sets with no written justifications.

Quality system regulation – 21 CFR, Part 820
QSR – Subpart H – Acceptance Activities Section 820.86 Acceptance Status

Each manufacturer shall identify by suitable means the acceptance status of product, to indicate the conformance or nonconformance of product with acceptance criteria. The identification of acceptance status shall be maintained throughout manufacturing, packaging, labeling, installation, and servicing of the product to ensure that only product which has passed the required acceptance activities is distributed, used, or installed.

The first salient concept needing to be grasped, for achieving compliance to this requirement, is the identification “by suitable means the acceptance status of product.” Pretty simple, right? FDA insists that device makers clearly indicate the acceptance status of product, i.e., good versus bad, conforming versus nonconforming, accepted versus rejected, etc. The second salient concept that needs to be understood, in support of achieving compliance, is that acceptance status “shall be maintained.” In fact, acceptance status needs to be maintained throughout the entire manufacturing cycle. The expectation is that nonconforming devices be quickly identified, labeled, removed from the manufacturing cycle, quarantined, and assigned a disposition (check in again next week for a discussion on non-conforming product). The final salient concept that needs to be understood is that acceptance status tools, when effectively applied, will help ensure only finished devices that have passed all of their acceptance activities, will be “distributed, used, or installed.”

In simplifying the requirement, make sure your organization pursues the following steps:

1. Establishing a proactive approach to line clearance;
2. Ensuring all product, on the manufacturing floor, is properly identified in regards to batch, quantity, and acceptance status;
3. Ensuring all finished devices are properly identified with the appropriate acceptance status;
4. Employing routers that clearly define each manufacturing, test, or inspection operation;
5. Ensuring operators sign off each process sequence delineated within the router, with name and date, as each sequence is completed; and
6. Ensuring all of these activities, including the final acceptance status, are included in the Device History Record (DHR).

Conclusion: Label product to reflect correct acceptance status
There is really just one takeaway for this edition of DG; ensure all devices are properly labeled with the appropriate acceptance status. In Dr. D’s world, green equates to good and red equates to the opposite of good, or should I say bad. Remember folks, this is not rocket science being presented here, just the fairly mundane task of labeling product to reflect correct acceptance status.

Since I was unable to locate specific enforcement violations of 820.86, the doctor is going to assume this QSR requirement is completely understood. 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 – I (Non-Conforming Product), specifically (820.90) – 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 10, 2010, from http://www.fda.gov/ICECI/EnforcementActions/WarningLetters/