Happy New Year! Dr. D hopes that all of the readers of Devine Guidance (DG) have a healthy and prosperous 2017. For those of you who have perused through the doctor’s last article of 2016, Dr. D apologizes for an error in referencing a quote made famous by Humphrey Bogart in the movie Casablanca. A dear friend of Dr. D’s (Richard—and yes, the doctor does have a few friends) pointed out the doctor’s incorrect quoting of “Play it again, Sam” versus the actual quote in the move “Play it, Sam. Play As Time Goes By.”

It is kind of funny how the little things in life, such as failing to adhere with a written procedure, can result in a Form 483 observation during an inspection. In fact, rack up a few teensy, weensy Form 483 observations during a friendly visit from the agency for a cup of coffee and an inspection and a warning letter just might mysteriously appear on the desk of the chief jailable officer (CJO) a few weeks after an inspection. That being said, preventive maintenance (PM) activities are a plant manager’s best friend. Not only are such activities that protect investments made in often-expensive capital equipment, but PM also keeps the production line flowing with innovative products. However, there is nothing quite like that immutable (look-it-up) link between a line-down scenario and the interruption of the supply chain to dampen the mood of the CFO, COO, CTO, CEO, CJO, and ultimately the customer. Enough acronyms for you? Enjoy!

Warning Letter – August 5, 2016

At first glance, the warning letter issued to an establishment back in the summer of 2016 appears to be fairly innocuous (look-it-up). However, if the offending establishment tried something novel such as following some of their written procedures, the outcome of the inspection just might have been different. After all, one of the basic tenants of any quality management system (QMS) is the establishment of procedures. In the eyes of FDA, the term establish is defined as: (a) define, (b) document and (c) implement. There is not much clarification required; simply stated, script and follow your procedures.

Additionally, failing to adhere to a procedure targeting the preventive maintenance of manufacturing and inspection equipment is not unlike poking a sleeping bear in the eye with a sharp stick. Bad things are going to happen, and happen quickly. PM procedures are used to keep manufacturing and inspection equipment in tip-top shape. In fact, the well-being of the equipment and the mental well-being of the operation’s manager are premised on a good PM program keeping the equipment fully operational.

Furthermore, failure to follow procedures is always going to draw the ire from our friends from FDA. Why? Well, if you have to ask why, you are probably in the wrong industry. Maybe flipping burgers might be a viable option.

Warning Letter Excerpt

Observation One (5) – Failure to establish and maintain schedules for the adjustment, cleaning and other maintenance of equipment to ensure that manufacturing specifications are met, as required by 21 CFR 820.70(g)(1). Specifically, your “Equipment Preventive Maintenance” schedule, 07-SRG-005, revision 4, is not being implemented in that:

a)  The schedule states for the (b)(4) Water, which is used to purify the water used in manufacturing the Hemolysis and Wash Solution, to “Replace Cartridges and sanitize bowl/heads 1 yr or if pressure becomes too high”. Your procedure does not specify a pressure limit but the (b)(4) instruction manual states the cartridge should be changed “with a membrane cartridge installed in Bowl #4, and the pressure differential between #3 exceeds 10 psi”. Device History Records for Lots HW-389-JU and HW-380-JU each showed a 20 psi pressure differential. The cartridge has not been replaced.

b)  The schedule states for the Main Warehouse Refrigerator to “Inspect quarterly (TSMD log)”. There are only 3 “WALK IN COOLER/FREEZER” forms completed in 2015 and there are no forms/records of inspection for 2016.

Your response cannot be assessed at this time. You state that you will revise your procedures to reference the appropriate documentation for the (b)(4) system in use; and will review your procedures for the Refrigerator Maintenance and assure the PM is completed by August 30, 2016. Please provide an update regarding your corrective action.

21 CFR, Part 820.70 – Production and Process Controls

(g) Equipment. Each manufacturer shall ensure that all equipment used in the manufacturing process meets specified requirements and is appropriately designed, constructed, placed, and installed to facilitate maintenance, adjustment, cleaning, and use.

Compliance for Dummies

Dr. D cannot place enough emphasis on the need to script and follow procedures. Obviously, procedures for PM are important to ensure manufacturing and inspection equipment remains fully functional and capable of producing finished medical devices that are safe and effective in their intended use. However, equally important is the need for device establishments to comply with 21 CFR, Part 820, the quality system regulation (QSR).  Now old Dr. D knows a thing or two about maintaining manufacturing and inspection equipment, including the importance of calibration. Conversely, the old doctor knows the ramifications when manufacturing equipment breaks due to improper preventive maintenance. Not only does the manufacturing line come to a screeching halt, depending on the severity of the equipment failure, the CFO may have to affix his or her signature to some very large checks.

Equally expensive can be the potential loss of revenue when the supply chain is interrupted or a visit from the FDA results in multiple Form 483 observations, or even worse, a warning letter. Once that warning letter becomes public knowledge, an establishment’s sales take an enormous hit. Additionally, if an establishment has regulatory submissions planned for submission or submissions currently residing with FDA, the review process essentially stops. Furthermore, if a device establishment is on the receiving end of an agency warning letter, Certificates to Foreign Governments (CFGs) begin to collect a significant amount of dust, as these documents needed to export medical devices outside of the United States are no longer signed by FDA. You see, when an offending establishment is awarded a prized FDA warning letter, the agency believes correcting the compliance issues are much more important than filling up the new product pipeline or expanding sales through an increase in commercialization outside of the United States. Think about it, something as benign as failing to establish a procedure required by the QSR could result in bringing a device establishment to its proverbial knees (regardless of an organization’s size). Remember, the FDA just does not care, as small establishments are held to the same compliance standard as Fortune 500 giants; and when severe compliance issues are noted, the FDA wants these issues fixed. Remember, it is the FDA’s sandbox so to play in that sandbox device establishments must abide by the agency’s rules.

Takeaways

For this inaugural DG for 2017, the doctor will leave the readers with two takeaways. One: Preventive maintenance is an important yet sometimes overlooked activity that is imperative for keeping the manufacturing and inspection equipment functioning properly and the supply chain flowing. Two: Failure to follow procedures for PM can have a devastating effect on manufacturing and inspection equipment. When equipment fails due to poor maintenance habits, the supply chain comes to a screeching halt as manufacturing stops. Equally as devastating is the compliance side of not establishing or failing to follow procedures. If the FDA is convinced that the compliance levels associated with failing to establish or comply with procedures is severe, then a warning letter will be in an offending establishment’s future (no crystal ball required). Remember, an agency warning letter can have an equally devastating effect on an offending establishment’s supply chain. In closing, thank you again for joining Dr. D, and I hope you found value 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 2015). Title 21 Part 820: Quality system regulation. Washington, D.C.: U.S. Government Printing Office.
2. Code of Federal Regulation. (April 2015). Title 21 Part 803: Medical device reporting. Washington, D.C.: U.S. Government Printing Office.
3. Devine, C. (2011). Devine guidance for complying with the FDA’s quality system   regulation – 21 CFR, Part 820. Charleston, SC: Amazon.
4. Devine, C. (2013). Devine guidance for managing key attributes of a FDA-compliant quality management system – 21 CFR, Part 820 Compliance. Charleston, SC: Amazon.
5. FDA. (August 2016). Inspections, Compliance, Enforcement, and Criminal Investigations. Tosoh Bioscience, Inc. Accessed January 9, 2017. Retrieved from http://www.fda.gov/ICECI/EnforcementActions/WarningLetters/2016/ucm516914.htm