It is Dr. D’s humble opinion that the calibration of measuring and monitoring equipment is considered one of the basic elements of a quality system, regardless of industry. How can an establishment design, develop, manufacture and enter into commerce medical devices that are safe and effective in their intended use if their measuring and monitoring equipment is not calibrated? In fact, during a recent FDA visit to an establishment in Florida, an agency investigator had the same question when he or she showed up in the lobby for a cup of coffee and an inspection. There is no doubt in the doctor’s twisted mind that the Chief Jailable Officer (CJO) was not in a jocund (look-it-up) mood when the investigator started handing out Form 483 observations faster than Clark Kent changing his clothes in a telephone booth. What’s a telephone booth Dr. D? Enjoy!

Warning Letter – December 9, 2015

The FDA traveled to a device establishment located on Florida’s Gulf Coast and spent two glorious days ripping an out-of-compliance establishment a new one. During a two-day period, the agency awarded the offending establishment eight Form 483 observations. Unfortunately, the poorly written response, received by FDA in early October, did not result in the offending establishment ingratiating themselves with the agency. The response probably just ticked off the reviewer. Oops!

Warning Letter Excerpt

“We received your written response on October 5, 2015, concerning our investigator’s observations noted on the Form FDA 483, Inspectional Observations (FDA 483) issued to you. In your response, you failed to outline the specific steps for each observation that you will take to establish and follow written procedures and policies to comply with current FDA regulations, therefore; your response is inadequate.”

Observation Three  – “Failure to establish procedures to ensure equipment is routinely calibrated, inspected, checked, and maintained which is required by 21 CFR 820.72(a).

For example, your firm has failed to establish procedures or a calibration frequency for the optical comparators, micrometer, and dial calipers used in the production and inspection of your ceramic orthodontic brackets. In addition, you did not have documentation to show this equipment is calibrated to ensure that the equipment is suitable for its intended purpose and is capable of producing valid results.”

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, the calibration of inspection, measuring and monitoring equipment is mandated by 21 CFR Part 820.72. Simply stated, this requirement is not optional. The good news is calibration (a.k.a., metrology) is not that difficult of a requirement to achieve compliance. For starters, there are many qualified metrology laboratories scattered around the globe that are capable of handling a device establishment’s metrology needs. On the left coast, Dr. D frequently comes across the same three key players: (a) RS Calibration, (b) Simco, and (c) PMI (note: the doctor is not a paid spokesman for any of these facilities). However, regardless of location, the key in selecting a good metrology lab is ensuring the facility is ISO/IEC 17025:2005 accredited. If the accreditation does not exist, then find another source, Dr. D must insist (sounds like an OJ Simpson trial rhyme the doctor came across years ago, something about a glove).

Dr. D strongly recommends outsourcing calibration, if an establishment does not have the resources and time to commit for managing a calibration program internally. Regardless, FDA still requires a procedure that clearly delineates how the calibration program is being executed. Additionally, if calibration is going to be performed internally, procedures need to be scripted for how each instrument is going to be calibrated. For example, if calipers, micrometers, dial indicators, etc. need to be calibrated, the procedure(s) must be specific to each type of gage. Furthermore, the gages employed as part of the calibration process need to calibrated and traceable to a national standard. In the United States, traceability to National Institute of Standards and Technology (NIST) would be the requirement for traceability. Please note, these transfer standards need to be locked away with their use restricted to calibration.

So what does the FDA consider compliant from a calibration system perspective?

1. As previously mentioned, a well-written procedure is a salient requirement. The procedure will need to clearly address the “handling, preservation, and storage of equipment, so that its accuracy and fitness for use are maintained.”
2. The procedure(s), regardless of the calibration being performed internally or outsourced, need to include “specific directions and limits for accuracy and precision.”
3. When equipment is found to be out-of-tolerance, remedial activities need to be pursued to bring the equipment back into calibration.
4. When nonconforming (out-of-tolerance) equipment has been identified, devices previously accepted must be assessed for any potential adverse effect induced as a result of being accepted using out-of-tolerance measuring equipment.
5. If a device establishment develops its own calibration standard, the standard shall be documented and validated, as appropriate.
6. Equipment shall be appropriately labeled with a calibration status tag that indicates: (a) equipment identification (e.g., asset tag number), (b) date calibrated, (c) date calibration due, and (d) individual performing calibration (initials are acceptable).
7. All calibration activities shall be appropriately documented.
8. If calibration is performed by a metrology service, it is expected that the device establishment review the calibration certificates upon receipt for accuracy and/or adverse trends when compared to previous calibrations (recommend getting a stamp to document each review).
9. Records associated with calibration shall be clear, concise, current and readily available.

Takeaways

For this week’s guidance, Dr. D will leave the readers with three takeaways. One: Because the calibration of measuring and monitoring equipment is such an important element of the quality management system, the doctor always recommends outsourcing calibration to a qualified metrology service. Two: If an establishment decides to assume the responsibility for calibrating all of their own equipment, make sure the calibration procedures are well written. Three: If a decision is made to develop a custom calibration standard, ensure the use of a custom calibration standard is appropriately documented and calibrated, as appropriate. 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.

References

1. Code of Federal Regulation. (2015, April). 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. (December 9, 2015). Inspections, Compliance, Enforcement, and Criminal Investigations. LAR MFG., LLC. Accessed February 16, 2016. Retrieved from http://www.fda.gov/ICECI/EnforcementActions/WarningLetters/2015/ucm482453.htm