No Control
For this week’s Devine Guidance (DG), Dr. D will focus on the control of non-inventory items. While traversing through the FDA’s warning letters, the doctor was able to find a warning letter that references the seldom cited 21 CFR, Part 820.70(h). Now some of you readers may vehemently disagree with Dr. D’s next two comments and the doctor apologizes in advance. One: There is no requirement to perform receiving inspection on all materials that come into a facility that are eventually used in the manufacture of finished medical devices. Two: Lot control is not required on all of the materials used during manufacturing. What, are you crazy, Doc? Seriously, receiving inspection is a tool that should be driven by risk. However there are many disposable items (a.k.a., floor stock or non-inventory items) that are needed in support of manufacturing operations. These items, such as finger cots, lint-free-wipes, alcohol (obviously not the drinking kind such as good bourbon), mandrels, purified water, etc., are quickly disposed of after their use. There may be a requirement for material identification; however, assignment of batch numbers and traceability may not necessarily be a requirement. Now as an old quality and regulatory guy, Dr. D hates defensive receiving inspection. In fact, the doctor’s doctoral dissertation focused on the benefits and at times, not so beneficial aspects of receiving inspection (RI) for medical device establishments. Sometimes RI is a necessary evil and sometimes RI is just evil, considering the resources and fiscal challenges associated with the entire RI process. So what happens when our dear friends from the FDA magically appear in an establishment’s lobby for the friendly cup of coffee and an inspection? In a perfect medtech world, the Chief Jailable Officer reviews the Form 482 (U. S. inspections only), escorts the investigator(s) to the conference room, and fetches some coffee. However, once the inspection commences, all bets are off. If the inspection is going poorly, it is a difficult task indeed for the CJO to repudiate (look-it-up) inspectional observations without documented evidence of compliance such as acceptance criteria for raw materials, adequate material controls on the manufacturing line, and sufficient identification and traceability of materials employed during manufacturing. Enjoy.
Warning Letter – May 1, 2017
As mentioned in the introduction to this week’s DG, issues related to non-inventory items and associated controls are not routinely cited. In fact, the doctor is struggling to see what the concerns may have been over non-inventory items not being inspected, as referenced in Observation Two of this week’s warning letter. The doctor was not there so trying to determine the whys would be purely conjecture on the doctor’s part. Simply stated, the doctor seldom, if ever, sees non-inventory items going through RI. In many instances, this material is placed on a ship-to-stock program or Kan Ban program and bypasses inspection completely. However, device establishments do need to identify, with sufficient granularity, their process for managing non-inventory items, including any requirements for identification and traceability, and rationale for why inspection is not warranted. A procedure for the identification, traceability, storage and handling of non-inventory items is all that is really required to placate FDA. Just stating the fact that an item is categorized as “non-inventory” is probably going to be problematic for the offending establishment; and result in the investigator(s) writing a Form 483 Observation.
Warning Letter Excerpt
Observation Two (2) – “Failure to establish and maintain adequate procedures for the use and removal of manufacturing material to ensure that it is removed or limited to an amount that does not adversely affect the device’s quality, as required by 21 CFR 820.70(h). For example:
On March 31, 2017, a (b)(4) was found ripped and taped shut with packing tape. Inspection revealed this material was classified as “non-inventory”, lacked acceptance criteria, and was accepted with no record of inspection. Our investigator also noted your firm stored these (b)(4). These (b)(4) come in direct contact with and are used in the cleaning of cranial implants.”
21 CFR, Part 802.70 – Production and Process Controls
(h) Manufacturing material. “Where a manufacturing material could reasonably be expected to have an adverse effect on product quality, the manufacturer shall establish and maintain procedures for the use and removal of such manufacturing material to ensure that it is removed or limited to an amount that does not adversely affect the device’s quality. The removal or reduction of such manufacturing material shall be documented.”
Compliance for Dummies
Manufacturing material, regardless of its classification, needs to be adequately controlled throughout product realization, period! Now the previous statement does not mean full-blown inspection prior to placing the material into a kit that finds its way to the manufacturing floor. However, it does imply that some level of control is warranted. In the medical device manufacturing world, materials are:
- Procured (from qualified suppliers)
- Inspected and tested (as appropriate)
- Placed into inventory
- Picked and placed into kits
- Kits moved onto the manufacturing floor (through a pass-through if manufacturing occurs in a Controlled
- Environment Room (CER) (a.k.a., cleanroom)
- Assembled into finished medical devices
- Finished medical devices are packaged to protect them from damage
- Shipped to sterilization supplier (if terminally sterilized is a requirement)
- Finished devices are placed into stores
- Shipped into commerce when orders are received
All of the aforementioned steps are pretty typical for medical device manufacturing facilities. At each step, there may be a requirement to use non-inventory items, even sterilization with empty boxes for dunnage. Because of their frequent use in manufacturing, non-inventory items need to have some level of control. That is why a procedure defining the controls of non-inventory material is so darned important.
Although the not every material used as part of the manufacturing process is required to be placed under batch management or be inspected upon receipt (e.g., non-inventory items), if a material is expended during manufacturing, it should be listed in the bill of materials (BOMs) and identified in the Manufacturing Process Instructions (MPIs).
Additionally, when a lot has passed through a workstation, with the exception of non-inventory items such as alcohol, wipes, finger cots, etc., there should not be any residual components remaining. Not unlike working on your car, having leftover parts is probably going to be a bad thing.
Finally, at the end of each manufacturing shift, workstations really do need to be cleaned. All residual work (including travelers) should be properly protected and covered. Non-inventory items should be returned to their bins or returned to their kit until manufacturing resumes. The last thing FDA investigators want to see are manufacturing stations that are messy, cluttered, and piled high with non-inventory items. In Dr. D’s warped brain, well-organized workstations equate to efficiency and reduce the potential for lot mix-ups.
Takeaways
For this week’s guidance, the doctor will leave the readers with two takeaways. One: Once all work has been completed at a work station, all residual materials need to be: (a) accounted for and removed from the work station, (b) returned to their kit box, (c) returned to stock, or (d) appropriately stored at the work station—including non-inventory items. Two: Not all material requires inspection or lot traceability (a.k.a., “non-inventory” items). However, device establishments need to clearly define the appropriate controls for non-inventory items. The requirements should be documented in a procedure and the use of these items captured in a MPI and lot traveler, as appropriate. 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
- Code of Federal Regulation. (April 2016). 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. (May 2017). Inspections, Compliance, Enforcement, and Criminal Investigations. Oxford Performance Materials. Retrieved from https://www.fda.gov/ICECI/EnforcementActions/WarningLetters/2017/ucm557872.htm.
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