Once again, Dr. spent another long week on the road playing road warrior. On a positive note, that gave the doctor plenty of time for drinking and thinking. That being said, this week’s guidance is also premised on one of the doctor’s visits to the FDA’s enforcement page, during a long flight, and the opportunity to traverse the warning letters for weekly cannon fodder.
For this week’s guidance, the doctor came across another interesting violation of the QSR, environmental controls. If a medical device establishment is manufacturing sterile medical devices, Dr. D is not sure how environmental monitoring and the calibration and servicing of environmental control systems are not part of the product realization equation. For you non ISO 13485-types, that means manufacturing. In fact, the doctor “asseverates” (look-it-up) that controlled environments must always be monitored and the results recorded as objective evidence of compliance. If objective evidence is not recorded, than in the eyes of FDA, the event or activity never occurred. Before jumping into this week’s guidance, if you are your organization’s Chief Jailable Officer (CJO), then you know how much fun it is sitting across from an FDA investigator without objective evidence of compliance. Enjoy!
This week’s warning letter was issued to a Chinese company that manufactures catheter insertion kits, blood piercing devices, and surgical forceps. Clearly these devices are sterile and the expectation is that they are being manufactured in a controlled environment. However, without written procedures that define the controls such as temperature, humidity, positive pressure, particulate counts, acceptable-levels of bio-contamination (including action and alert limits), servicing of HEPA filtration systems, servicing of air handler units, and the calibration of measuring and monitoring equipment, then there is zero chance of being able to claim compliance in the eyes of FDA. The warning letter excerpt presented in this week’s guidance was their reward as a result of a less than stellar inspection.
Warning Letter Excerpt – 19 September 2013
Failure to establish and maintain procedures to control environmental conditions that could reasonably be expected to have an adverse effect on product quality and failure to periodically inspect environmental control systems to verify that the system is adequate and functioning properly, as required by 21 CFR 820.70(c). For example, (b)(4) results for the (b)(4) area were not documented from February 2013 through June 2013.
Subpart G – Production and Process Controls
Sec. 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.
Environmental Control – Basic Requirements
For this week’s guidance, the doctor will be brief. Dr. D strongly recommends the process commence with the scripting of a series of Standard Operating Procedures (SOPs). The doctor recommends that you consider the following SOPs or ensure that these requirements are addressed in existing SOPs and/or work instructions:
- A procedure for gowning and hygiene of personnel appropriate for clean room (controlled environment) entry;
- An environmental controls procedure that delineates the requirements for monitoring and recording of temperature, RH, airborne particulate counts; and work-surface contamination limits (number of colony forming units – CFUs);
- A procedure for product cleanliness;
- Requirements for packaging soon-to-be sterile medical devices in a controlled environment; and
- Validation(s) to support the controlled environment capable of providing stable and repeatable results.
Additionally, the doctor strongly recommends the use of qualified suppliers, to perform all of the testing, maintenance, and validation activities, if the decision is made to outsource this work. Can you say ISO/IEC 17025:2005? There are many reputable firms available that can validate the environmental operating conditions associated with your controlled environment and keep it humming along, well below your specified alert limits (hopefully).
The best advice the doctor can offer in regards to standard utilization is the ISO 14644 series of standards. As a minimum, Dr. D recommends that the following ISO standards be considered and applied:
- ISO 14644-1:1999 (Clean Rooms and Associated Controlled Environments – Part 1: Classification of Air Cleanliness);
- ISO 14644-2:2000 (Clean Rooms and Associated Controlled Environments – Part 2: Specification for Testing and Monitoring to Prove Continued Compliance with ISO 14644-1); and
- ISO 14644-3:2005 (Clean Rooms and Associated Controlled Environments – Part 3: Test Methods).
If your organization employs compressed air, then ISO 8573-1:2010 (Compressed Air – Part 1: Contaminants and Purity Classes) should be considered. FYI – your notified body is going to ask to see compliance to ISO 8573-1, so it is better to be prepared.
For this week’s guidance Dr. D will leave the readers with four takeaways. One – Compliance begins with the scripting of well-written procedures. Two – The ISO 14644 series of standards are available to help guide organizations with clear and concise requirements for clean rooms (controlled environments). Three – Always select a qualified organization for the initial validation and subsequent testing of the controlled environment. Four – Just in case you haven’t figure it out yet, documented records/results for the monitoring of a controlled environment is a salient requirement for FDA.
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 – cheers from Dr. D. and best wishes for continued professional success.
- Code of Federal Regulation. (2013, April). 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.
- FDA – U.S. Food and Drug Administration Website. (2013, June). Warning letters. Retrieved October 12, 2013, from http://www.fda.gov/ICECI/EnforcementActions/WarningLetters/2013/ucm370051.htm