For this week’s Devine Guidance (DG) the doctor will take a quick peek into cleanroom monitoring requirements. According to FDA, the environmental conditions in cleanrooms require monitoring (§820.70(c)). In fact, during a recent inspection, the FDA cited an establishment for failing to monitor environmental conditions (temperature and humidity) within their cleanroom. Now maybe Dr. D is beginning to grow a little long in the proverbial tooth (the comment means getting old for you millennials out there); however, when has monitoring temperature and humidity in a cleanroom or controlled environment room (CER) not been a requirement? Every self-respecting quality and manufacturing engineer recognizes that if cyanoacrylates are employed in the manufacture of finished medical devices and subassemblies, the control of temperature and relative humidity (RH) is important in support of curing, especially the RH. If you do not want to believe Dr. D, just take a quick look at the curing curves provided by Loctite Corp. Most device establishments wanting to create a simulacrum (look-it-up) of compliance will strive to have a thorough understanding of the Quality System Regulation (QSR), including environmental monitoring. However, for device establishments that fail to understand the gravity of compliance, the Chief Jailable Officer (CJO) is in for some serious regulatory pain, courtesy of our dear friends from FDA. Enjoy!

Warning Letter – June 13, 2016

As alluded to in the introduction to this week’s DG, old Dr. D was a little surprised to find a device establishment cited for failing to monitor the environmental conditions in their cleanroom. By their very nature, these environments are created and maintained to facilitate the manufacture of finished medical devices that are safe and effective in their intended use. The cleanroom becomes extremely important when medical devices are being manufactured for use either inside the body or to introduce a medical device into the body where sterility is of the utmost importance.

Warning Letter Excerpt

Observation Three (3). “Failure to establish and maintain procedures to adequately control environmental conditions, where environmental conditions could reasonably be expected to have an adverse effect on product quality, as required by 21 CFR 820.70(c). For example, your firm does not monitor the environmental conditions, i.e. temperature and humidity conditions, in cleanroom (b)(4) where the (b)(4) process is conducted for the Adelante Magnum devices.”

“We reviewed your firm’s response and conclude that it is not adequate. While your firm’s response indicates that procedures will be revised and the use of production environmental monitoring records will be implemented, the response did not include documentation to this effect.”

21 CFR, Part 820.70 – Production and Process Control

§820.70(c) – Environmental Control

“(c) Environmental control. Where environmental conditions could reasonably be expected to have an adverse effect on product quality, the manufacturer shall establish and maintain procedures to adequately control these environmental conditions. Environmental control system(s) shall be periodically inspected to verify that the system, including necessary equipment, is adequate and functioning properly. These activities shall be documented and reviewed.”

Compliance for Dummies

From an environmental monitoring perspective, the doctor typically sees three elements being continuously monitored when it comes to ensuring a cleanroom is being adequately maintained:

1. Temperature
2. Relative humidity
3. Positive pressure, courtesy of the magnehelic gages

Additionally, particulate counts (e.g., viable air) and surface contamination (contact plates) testing is performed at defined intervals. In fact, the cleanroom really does need to be properly validated prior to use. The good news is there are establishments that can perform this work at a reasonable price for most device establishments (e.g., CTS – Murrieta, CA and CSI – Santa Clara, CA) and no, Dr. D  is not a paid spokesperson for these organizations.

Additionally, device establishments will need to determine their action and alert levels, including next steps for when environmental conditions are exceeded. A couple of years ago, the doctor was auditing an establishment and during the review of environmental records noted that the alert limits for particle counts had routinely been exceeded with no action taken. The reports clearly indicated that multiple areas within the CER had particulate issues but the quality engineer was just rubber stamping the report. What the heck? Why bother monitoring a cleanroom’s environment if the data is not going to be used to drive compliance? In fact, you might as well just assemble finished medical devices in the doctor’s garage. In fact, Dr. D will even throw in security, courtesy of the doctor’s three dogs.

Seriously, device establishments need to script a well-written procedure that defines the environmental monitoring requirements within their cleanroom or CER, including the action and alert limits. When these limits are exceeded, there must be some level of mitigation pursued. For example, Dr. D recommends always opening a CAPA when action limits are exceeded. However, if the environmental monitoring requirements have not been established, how can an establishment pursue formal corrective action?

Takeaways

For this week’s guidance, there is just one takeaway: Establish a well-written procedure for environmental controls, including control limits and alert limits—and then adhere to it. If bioburden loads and pyrogenicity are important influencers impacting your establishment’s medical devices, then compliance with established environmental requirements is not optional. If you do not want to believe Dr. D, just ask FDA. Please do not be that device establishment that fails to properly monitor their cleanroom. 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. 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. (June 2016). Inspections, Compliance, Enforcement, and Criminal Investigations. Oscor, Inc. Accessed July 23, 2016. Retrieved from http://www.fda.gov/ICECI/EnforcementActions/WarningLetters/2016/ucm509968.htm.