The calibration and preventive maintenance (PM) of manufacturing, monitoring, and measuring equipment is considered a fundamental task associated with any quality management system. Now granted, not every piece of equipment employed in the manufacture of finished medical devices that are safe and effective in their intended use requires calibration. That is why device designs and manufacturing processes are appropriately verified and validated. However, considering the investment made in the purchase of capital equipment, with very few exceptions, an active calibration and PM program should be pursued. Besides, when equipment is not in operation—i.e., (a) mill spindles turning and making chips (any device); (b) screw machines milling screws for orthopaedic devices, (c) injection molding machines kicking out plastic handles for catheters; or (d) extruders extruding reinforced PEBAX shafts for coronary ablation catheters—manufacturers are not making money. Regardless of industry, not making money is a bad thing. If you are a production or operations manager, there are few things in life more rebarbative (look-it-up) than a piece of manufacturing equipment breaking down due to poor PM or an overall lack of a PM program. Enjoy!
Warning Letter – 12 June 2015
Receiving a Form 483 observation for failing to perform calibration and maintenance activities on injection molding machines is a relatively rare event. Considering the investment dollars required to purchase a state-of-the-art plastic injection molding machine and the need to properly facilitate its installation, not only should installation qualification, operational qualification and performance qualification be considered, but also a robust PM program (including calibration) must be implemented. Otherwise, when our dear friends from the agency show up for a cup of coffee and an inspection, bad things are bound to happen, as you can see from reading Observation seven (7) extracted from this week’s recipient of a prized agency warning letter.
Observation Seven (7). “Your firm failed to establish procedures to ensure equipment is routinely calibrated, inspected, checked, and maintained, as required by 21 CFR 820.72(a). Specifically, (b)(4) injection molding machines have been installed in your facility. AG Equipment Number (b)(4). Maintenance logs for these three pieces of equipment do not include any calibration activities or instrumentation inspection since the date the equipment was installed.”
21 CFR Part 820.72 – Inspection, Measuring, and Test Equipment
(a) Control of inspection, measuring, and test equipment. Each manufacturer shall ensure that all inspection, measuring, and test equipment, including mechanical, automated, or electronic inspection and test equipment, is suitable for its intended purposes and is capable of producing valid results. Each manufacturer shall establish and maintain procedures to ensure that equipment is routinely calibrated, inspected, checked, and maintained. The procedures shall include provisions for handling, preservation, and storage of equipment, so that its accuracy and fitness for use are maintained. These activities shall be documented.
(b) Calibration. Calibration procedures shall include specific directions and limits for accuracy and precision. When accuracy and precision limits are not met, there shall be provisions for remedial action to reestablish the limits and to evaluate whether there was any adverse effect on the device’s quality. These activities shall be documented.
(1) Calibration standards. Calibration standards used for inspection, measuring, and test equipment shall be traceable to national or international standards. If national or international standards are not practical or available, the manufacturer shall use an independent reproducible standard. If no applicable standard exists, the manufacturer shall establish and maintain an in-house standard.
(2) Calibration records. The equipment identification, calibration dates, the individual performing each calibration, and the next calibration date shall be documented. These records shall be displayed on or near each piece of equipment or shall be readily available to the personnel using such equipment and to the individuals responsible for calibrating the equipment.
Compliance for Dummies
Folks, for starters when a Part 820 requirements states the infamous “shall establish” (establish means to define, document (in writing or electronically), and implement), you just might want to start writing that SOP. In support of meeting calibration and PM requirements, the FDA requires each manufacturer to establish and maintain procedures to ensure that equipment is routinely calibrated, inspected, checked and maintained. Please note, the requirement does not grant any special dispensation, e.g., “some equipment”. The best advice Dr. D can offer is to open the manual that accompanies the piece of equipment that was just received, installed, etc., and read about the calibration and maintenance requirements. Once you finish reading, you can start scripting the procedure using the manufacturer’s specification. For example, if time, temperature, and pressure are required to be controlled and the manual states as much guess what? You have to define those parameters in a procedure and provide specific limits needed for calibration.
If the manufacturer’s maintenance instruction states that certain filters need to be replaced monthly or the oil sump must be checked after so many operational hours, guess what? This needs to be placed into a PM procedure. If an external third-party service provider is retained to perform the PMs on equipment, the supplier must be appropriately qualified and placed on the approved supplier list (ASL). If the third-party service provider its their own documentation, it is incumbent upon the establishment to ensure this documentation is aligned with the manufacturer’s requirements.
Additionally, not wanting to state the obvious but obliged to do so, Dr. D always recommends employing a qualified metrology service for routine calibration of measuring and monitoring equipment. Yes, many organizations attempt to manage routine calibration in-house to save money. However, if the calibration program and work instructions employed to calibrate each instrument are not robust and in accordance with manufacturer requirements, then expect bad things to happen Also, it is imperative that the metrology service selected be appropriately qualified—and that means being the proud owner of an ISO/IEC 17025:2005 accreditation from a qualified and reputable accreditation body (e.g., A2LA – The American Association for Laboratory Accreditation).
Furthermore, the FDA requires that calibration be traced back to a national standard. Folks, in these United States of America that standard would be NIST, a.k.a., the National Institute of Standards and Technology. If your metrology supplier (listed on your ASL) is ISO/IEC 17025:2005, than you can take it to the proverbial bank that traceability to NIST exists.
Finally, if an activity or event is not documented in writing, in the eyes of FDA it never happened. It is imperative that the individual and/or organization tasked with managing calibration and PMs keep meticulous records. Why? Because no Chief Jailable Officer (CJO) wants to be sitting across from an FDA investigator with zero documented evidence of compliance to Part 820.72 or any other part of the Quality System Regulation (QSR).
For this week’s guidance, the doctor will leave the readers with four takeaways.
- The QSR requires that calibration and maintenance procedures be established. Stop stalling and start typing.
- Make sure the metrology source selected by your establishment is appropriately qualified to ISO/IEC 17025:2005 requirements.
- Traceability to back to NIST is a salient requirement in the United States. Just comply baby.
- Keep impeccable records of calibration and PM activities. Your CJO will thank you.
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. (2014, 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.
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 2015). Inspections, Compliance, Enforcement, and Criminal Investigations. AG Industries, Warning Letter. Accessed June 23, 2015. Retrieved from http://www.fda.gov/ICECI/EnforcementActions/WarningLetters/2015/ucm451494.htm