The US FDA's insistence on laboratory audits begs two pertinent questions: i) What is so critical about laboratory audits and more specifically the calibration of lab equipment, and ii )who is best suited to calibrate lab instruments in accordance with FDA standards?
The FDA guidelines clearly underline the need for laboratories to submit results of their audits: “ We recommend that all laboratories be audited at least once every 2 years, and that newly accredited laboratories, or accredited laboratories that add new methodologies to the scope of their accreditation, be audited more frequently.”
The emphasis on lab audits has to do with the general requirements for the competence of testing and calibration of laboratories. The task of the audit bodies is to assess whether the laboratory is qualified to use the specific methods that produce the data and test results that are submitted to the FDA.
Laboratories conform to the stringent FDA calibration standards more often than not. But, for first timers going through the rigmarole of regulations and standard practices, finding the right benchmark for FDA standards can be a nerve wracking exercise. They can struggle to find where to go to get their lab instruments calibrated for FDA standards.
So, who is best suited to get your lab checked for FDA standards and calibration? The bad news is: very few calibration experts can tell you up front what the FDA calibration standards are. The good news is: The FDA calibration standards are well enumerated in one of the sections of 21Code of Federal Regulations (CFR).
FDA's Code of Federal Regulations (CFR) - Points to remember:
It is always better to adhere to the CFR to get your instruments calibrated for FDA standards. The codes relate to: 1) Good laboratory practice for nonclinical laboratory studies (part 58) 2) current Good Manufacturing Practice (cGMP) for finished pharmaceuticals (part 211) 3) cGMP for blood and blood components (Part 606) 4) cGMP in packing or holding human food equipment and utensil maintenance (Part 110) e) cGMP governing the methods used in the design, manufacture, packaging, labelling, storage, installation and servicing of all finished devices meant for human use.
Other hurdles to overcome to calibrate your lab:
Part 820.72 of CFR makes it mandatory on the part of the manufacturers to ensure 1) All measuring and test equipment, inspection are capable of producing valid results 2) Equipment is routinely calibrated, inspected, checked, and maintained as per set procedures 3) Procedures shall comprise handling, preservation, and storage of equipment to maintain its accuracy and fitness 4) Activities are documented.
Why bother about Calibration records?
“It is imperative to be very particular about the paper work and records of calibrations done on set of instruments or any particularly instrument,” advises Ralph Sabiel, the Calibration Expert at R.S Calibration Services.
Proper documentation is critical regarding:
• individuals carrying out each calibration
• identification of equipment
• dates when calibration was performed
• date of next calibration
The documents should be kept close to the instrument it is related to.
What standards apply to which equipment?
Each calibration has to meet the basic standards, whether national or international standards. In the absence of both it becomes incumbent on the manufacturer to use an independent reproducible standard. Further, if there are no applicable standards available then an in-house-standard has to be maintained by the manufacturer.
Is lab calibration a long road?
In our lab, we are almost at our goal of meeting the FDA benchmark calibration for our instrument. For the final steps of the journey FDA 21CFR part 820.72, as described earlier, will be our Bible: “When accuracy and precision limits are not met, there shall be provisions for remedial action to re-establish the limits and to evaluate whether there was any adverse effect on the device's quality. These activities shall be documented.”
A few final steps for calibration:
• Keep the record straight. All the calibration process or procedures performed on all test equipment used for making quantitative measurement must be put in black and white on a piece of paper. Recalibration of equipment, whenever required, needs to be done on a regular basis
• Use the information gathered in the course of previous calibrations along with documented, validated and updated data to improve calibration procedures
• Keep calibration records (include as-found as left, standard reading from calibration) - an important component of QCP (Quality Calibration Programme).
• Absent data, it is not just possible to establish that tolerances and standards were met at the time of their use. It will also be difficult to ensure that correct calibration intervals and dates were calculated.