GMP Calibration – understand both EU and USA GMP requirements
Around a pharmaceutical manufacturing site there will be many measuring devices that require GMP calibration. GMP requires the calibration of such devices, with similar requirements in both EU and USA GMP, as can be seen below:
EU GMP (Chapter 3.41)
“Measuring, weighing, recording and control equipment should be calibrated and checked at defined intervals by appropriate methods. Adequate records of such tests should be maintained.”
USA GMP (21CFR211.68)
“Equipment … shall be routinely calibrated, inspected, or checked according to a written program designed to assure proper performance. Written records of those calibration checks and inspections shall be maintained.”
Calibration is a very important part of any organisation’s Quality System, yet its coverage in both EU and USA GMP is somewhat limited to the two clauses above. These two requirements do raise a number of questions that GMP does not answer. For example, in EU GMP, what is an “appropriate method” for calibration? In both EU and USA GMP what does “routinely calibrated” and “defined intervals” actually mean? Every month, every 6 months, every year, every 10 years?
One standard you could look at to get a more detailed series of requirements for calibration is ISO 9001. Its requirements are summarised below.
ISO 9001 (Clause 7.6)
Measuring equipment shall
a) be calibrated … at specified intervals … against measurement standards traceable to … national measurement standards …
b) be adjusted or re-adjusted as necessary
c) have identification in order to determine its calibration status
d) be safeguarded from adjustments …
e) be protected from damage and deterioration …
In addition, the organization shall assess and record the validity of the previous measuring results when the equipment is found not to conform to requirements. The organization shall take appropriate action on the equipment and any product affected. Records of the results of calibration and verification shall be maintained.
As you can see you get a lot more of an idea of what can be an “appropriate method” for calibration here. Much more depth about using calibration method traceable to national standards, adjusting the gauge if needed, considering the impact of batches affected if found out of calibration, appropriate identification and the need to protect from adjustment. Perhaps this depth of coverage of calibration comes from the history of ISO 9001, which was once more of an engineering/ military type standard.
None of these standards answer the question of when should you calibrate a gauge. Here we need to apply some common sense.
Firstly, establish if the gauge needs to be calibrated in the first place. Is it providing you with GMP/ quality related information that is essential for product quality or is it simply giving you “information only”. If it is for “information only” then it may not need calibrating. Examples of these are gauges on water systems that are simply indicating that the water is flowing at a certain speed. Quality critical data is recorded by other calibrated gauges at other locations.
Secondly, if the gauge does need calibrating then the frequency needs to be based on a number of factors. These can include:
- Manufacturer’s recommendations
- The frequency of calibration of identical or similar items of equipment
- The importance/ impact of the result, especially if it goes out of calibration
- The frequency of use of the item
- The extent that it is stressed during its use (i.e. is it used at the extreme limits of its designed range)
- The history of results
Once a calibration frequency is established it does not need to be “set-in-stone”. You could initially, for example, calibrate a gauge every 6 months for its first few years of use. After several years you could look at the data and consider extending that calibration frequency. You should also consider if the usage of the gauge has changed in this period, as this could affect any decision to change frequency (to less or more frequent).
Finally, ensure that your calibration activities are suitably recorded. These activities are often outsourced to specialist firms, so do check that they are providing you with calibration certificates that are suitable and will stand-up to regulatory inspection.
I hope you find this article of interest. Please feel free to comment or pass on to others. Don’t forget to visit our web-site for a range of GMP and Quality Management related courses.