The doctor has stated on many occasions that there are certain quality, regulatory and statutory requirements that fall into the category of basic blocking and tackling. It makes no difference as to what industry we work in or from which regulatory bible we read; there is always going to be a section that delineates the need for ensuring measuring and monitoring equipment to be appropriately qualified (and calibrated) for its intended use. Fail to do so in the medical device industry and bad things are going to happen. It is Dr. D’s strong opinion that §820.72 falls into that basic blocking and tackling category. AS 9100, ISO 13485, ISO 9001, ISO/IEC 17025, Part 820, Ministerial Ordinance 169, Part 211, etc. all have requirements associated with equipment qualification and/or calibration. The doctor also knows that Chief Jailable Officers (CJOs) will feel very uncomfortable sitting across from our dear friends from FDA, during that friendly agency visit for a cup of coffee and an inspection, if lapses in equipment qualification or calibration becomes readily apparent. The CJO will require no crystal ball to see that a Form 483 observation is in his or her establishment’s future. In fact, rack up a lucky 13 Form 483 observations and the awarding of a prized agency warning letter is almost guaranteed. Device establishments, with compliance issues, are viewed as being anathema (look-it-up) to the FDA and the agency’s need for establishments to sustain compliance. Enjoy!

Warning Letter – February 20, 2018

The warning letter recipient mentioned in this week’s guidance was on the receiving end of a 13-Form 483 Observation warning letter. Seriously, it is never going too well when the observations move into the double-digit range. Considering many of the observations noted in the warning letter fall into the basic blocking and tackling category such as lapses in document control, training, management review, and CAPA, the FDA was clearly sending a message. In fact, the CJO on the receiving end of the letter should probably plan for some very sleepless nights until the compliance issues are adequately addressed and the FDA placated.

Warning Letter Excerpt

Observation Four (4) – “Failure to adequately 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 according to established procedure, as required by 21 CFR 820.72(a). Specifically, your firm had no documentation that (b)(4) of testing equipment were qualified for their intended purpose per the associated standards.

We reviewed your firm’s responses and conclude that they are not adequate. The responses state that your firm plans to qualify the testing equipment. However, your firm’s responses do not include an action plan for a corrective action to prevent the recurrence of the issue.”

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

I am sure some of the readers have heard the saying you don’t bring a knife to a gun fight. Well (deep subject, the doctor knows), to some extent the same concept is true when selecting measuring and monitoring equipment or identifying gages for inspection. For example, if a cylinder-shaped component such as a catheter shaft of a guide wire has an outer diameter specified to be 0.003” ± 0.0005”, one does not measure the dimension with a caliper. A micrometer is the appropriate tool. Conversely, if an electronic system requires a high-resolution oscilloscope to measure a waveform, the appropriate piece of equipment is procured that is capable of obtaining the necessary measurements. Before the doctor forgets, unlike tossing a fragmentation grenade, accuracy counts, so measuring and monitoring equipment shall be appropriately qualified and calibrated.

Additionally, Dr. D is a big fan of test method validation (TMV). If you wish to ensure your establishments remain in the good graces of the FDA, TMV is a must have process. So what else do our friends from the agency look for when it comes to measuring and monitoring equipment?

For starters, the equipment, as the doctor as already alluded to, shall be suitable for its intended use. The FDA expects a well-written procedure or set of procedures that delineate requirements for calibration, preventive maintenance (PM), accuracy, storage, handling and preservation. Please note, only qualified individuals should be playing with the measuring and monitoring equipment.

When it comes to equipment calibration, it is ok to use qualified third-party metrology services. In Dr. D’s backyard, in the Silicon Valley, there are many qualified facilities capable of providing calibration support, such as Simco and RS Calibration (no, Dr. D is not a paid spokesman for these metrology labs). However, make sure your metrology service is ISO/IEC 17025 qualified. If you choose to calibrate your own tools, ensure that you have dedicated transfer standards (used only for calibration). Additionally, these standards need to be NIST traceable in the United States and to the appropriate national standards outside of the United States. If no standard exists, it is acceptable for an establishment to create their own standard. However, make sure the standard is appropriately qualified—e.g., robust TMV should be considered (hint, hint).

Furthermore, if a piece of measuring and monitoring equipment is found to be out-of-tolerance (failed calibration) an appropriate investigation shall be performed. The fundamental reason behind the investigation is quite simple. The device establishment needs to ascertain if the out-of-tolerance piece of equipment has resulted in nonconforming product being released to commercialization. Can you say, recall?

Finally, make sure all measuring and monitoring equipment is appropriately identified. A calibration label should be affixed to each piece of equipment that contains relevant information such as: (a) equipment serial or asset number, (b) date calibrated, (c) date due calibration, and (d) calibrated by information (technician). If the tool is too small for a label, the appropriate calibration information should be retained in a file near to where the equipment is used. Remember, if calibration activities are not documented in writing, they never happened.

Takeaways

For this week’s guidance the doctor will leave the readers with three takeaways. One: Applying the appropriate controls to measuring and monitoring equipment is considered basic blocking and tackling, baby. Two: Make sure your metrology service provider is ISO/IEC 17025 accredited. Three: Test method validation is a valuable tool when it comes to establishing a new measurement standard. In closing, thank you again for joining Dr. D, and I hope you found value (and some humor) 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 2017). 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. (February 2018). Inspections, Compliance, Enforcement, and Criminal Investigations. Dexcowin Co. Ltd., Accessed April 30 2018. Retrieved from https://www.fda.gov/ICECI/EnforcementActions/WarningLetters/ucm599697.htm