It is not often the doctor finds a warning letter that contains a reference to the violation of §820.130 requirements (Device Labeling). In this day and age of compliance requirements being enforced for the unique device identification (UDI) a.k.a., 21 CFR, Part 830; most device establishments have performed admirably when it comes to label controls and label accuracy. However, as labeling requirements grow more complex, so do the opportunities for making costly mistakes. If you have not noticed, the FDA continues to pay close attention to product labeling issues and has been known to write quite a few form 483 observations when labeling issues are noted during an inspection. In fact, many chief jailable officers (CJOs) have suffered through countless sleepless nights when product labeling issues have resulted in a market correction or removal. Can you say RECALL (that nasty 6-letter word)? Please keep in mind, there are very few drugs, legal ones anyway, that can provide the officinal(look-it-up) properties needed to resolve the sudden onslaught of regulatory pain when a CJO received that prized agency warning letter. Enjoy!

Warning Letter – October 20, 2017

As warning letters go, the letter referenced in this week’s guidance was fairly benign, with four observations cited. In fact, our friends from FDA decided to throw a zinger in the warning letter, citing an observation that was never included in the initial Form 483 observations. Ouch! It is the doctor’s opinion that this warning letter could have been prevented if the establishment provided a robust response supported by documented evidence of correction or a well-written plan containing timelines and objectives for correction. However, just stating that the corrections will occur is never going to be sufficient for FDA or any other regulatory organization for that fact.

Warning Letter Excerpt

Observation Three (3). “Procedures to control labeling activities have not been adequately established as is required by 21 CFR 820.120.

Specifically, your Device History Records do not contain label accountability, nor is a copy of each size label within a batch maintained, e.g., Batch (b)(4) contains (b)(4) pieces with (b)(4) different lengths. The DHR only contains a copy of the label for one size in the batch.

We reviewed your firm’s response and conclude that it is not adequate. The response indicates that corrections will be performed, but does not provide a plan, or documentation supporting that the correction has been performed.”

21 CFR, Part 820.120 – Device Labeling

“Each manufacturer shall establish and maintain procedures to control labeling activities.

(a) Label integrity. Labels shall be printed and applied so as to remain legible and affixed during the customary conditions of processing, storage, handling, distribution, and where appropriate use.

(b) Labeling inspection. Labeling shall not be released for storage or use until a designated individual(s) has examined the labeling for accuracy including, where applicable, the correct unique device identifier (UDI) or universal product code (UPC), expiration date, control number, storage instructions, handling instructions, and any additional processing instructions. The release, including the date and signature of the individual(s) performing the examination, shall be documented in the DHR.

(c) Labeling storage. Each manufacturer shall store labeling in a manner that provides proper identification and is designed to prevent mixups.

(d) Labeling operations. Each manufacturer shall control labeling and packaging operations to prevent labeling mixups. The label and labeling used for each production unit, lot, or batch shall be documented in the DHR.

(e) Control number. Where a control number is required by §820.65, that control number shall be on or shall accompany the device through distribution.”

Compliance for Dummies

Device labeling is much more encompassing then just the printed information placed onto the label stock and the label affixed to the product packaging (pouch, carton etc.). The FDA breaks the labeling requirements down into essentially five labeling buckets: integrity, inspection, storage, operations and control number (batch or serial number) assignment.

From an integrity perspective, labels shall remain readable and actually affixed to the box, carton, pouch or product as appropriate. The barcode associated with UDI requirements should actually be readable when scanned by a barcode reader. The labels need to remain intact during routine handling and transportation modalities. In fact, labeling is one of those activities that should be validated as appropriate. The validation should include the accuracy of the information being printed onto the label blanks.

Labels require inspection. Who knew? Seriously, not only should the label stock be inspection upon receipt, it should be verified prior to the label stock being released to production and again after the lot-specific information has been added to the label stock. This inspection activity shall be documented and a label retain affixed to the label inspection sheet. The results of the label inspection, including the name of the individual(s) performing the inspection and releasing the labels shall be documented. Dr. D recommends documenting this inspection on a label inspection form. A copy of a label retain can be affixed to the back of the label inspection form. This completed inspection form, including the inspection results, signatures, and label retain(s) shall be placed into the device history record (DHR) and kept as a quality record. Please remember, instructions for use (IFUs) are considered labeling and warrant the same kind of consideration as a physical label. They should be inspected and a copy of the IFU retained in the DHR.

Labels (storage and operations), prior to their use (printing) and during their preparation for use, must be appropriately stored and handled. Can you say line clearance is important? Good! It is equally important to have accurate labeling information versus ensuring the correct label is affixed to the correct device. Failure to do so will result in misbranded product, which can be the underlying reason for a market withdraw (RECALL). Having one label too many versus coming up one label short is also a problem when the inspector swears the number of labels released was accurate and in accordance with the shop floor paperwork.

Finally, if a batch number or serial number is required for a lot of devices or for a single device, it is imperative that lot segregation be maintained. Can you say line clearance (again)? Without lot integrity being maintained, it is not possible to manage activities such as corrections and removals (RECALL) when device issues force product removal from the field. Failure to maintain lot integrity could be the difference between recalling 20 suspect devices versus 20,000 suspect devices. If you want to mess with your CJO’s sleep patterns, fail to execute effective line clearance or maintain lot integrity.

Takeaways

For this week’s guidance, the doctor will leave the readers with one takeaway. An establishment can manufacture the most fabulous medical device in the world; however, if they cannot maintain label accuracy and lot integrity, it is all for naught. Unlike throwing an M-33 fragmentation grenade, accuracy counts when it comes to medical device labeling. Close but no cigar is never going to be an acceptable approach when “Truth in Labeling” counts. In closing, thank you again for joining Dr. D, and the doctor hopes 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. (November 2017). Inspections, Compliance, Enforcement, and Criminal Investigations. GPC Medical Ltd. Accessed January 15, 2018. Retrieved from https://www.fda.gov/ICECI/EnforcementActions/WarningLetters/2017/ucm589686.htm