An excerpt from the new GMP Series PDF Download Qualification and Calibration of Laboratory Instruments in Pharmaproduction
The calibration of analytical instruments is stipulated in the GMP Guidelines. During calibration, it is checked whether the qualified status of the instrument has been preserved. Non-calibrated analytical instruments may not be used for testing.
In accordance with the EU GMP Guidelines, Part I, calibration is defined as follows (cf. Figure 1):
Figure 1 Definition of calibration in accordance with the EU GMP Guidelines, Part I, Glossary (C.7 Glossary)
It is important to differentiate between calibration, and adjustment and gauging; they are defined as follows:
The calibration programme is used to ensure that all instruments are calibrated at regular intervals. The calibration programme can be described in an SOP that is the "higher-level" calibration SOP.
The general requirements that apply to all instruments are listed in Figure 2.
Figure 2 Contents of the calibration programme
The guidelines contain no mandatory requirements with regard to calibration intervals, the question of whether calibration should be carried out on a particular day or month, the scope of calibration or the definition of acceptance criteria. These must be defined internally based on experience. For this reason, the following examples are only suggestions.
The calibration intervals can be defined according to the priority of the instruments in the laboratory. Instruments with higher priority are calibrated at shorter intervals than those with lower priority. This approach is illustrated in the example in Figure 3.
Figure 3 Calibration intervals for laboratory instruments based on priority (example)
It is also possible and, in many situations, imperative to carry out the calibration before use, e.g. in the case of osmometers. This approach also makes sense in the case of instruments that are rarely used.
Because relatively short calibration intervals of 3 months and less are common in laboratories, it is recommended that calibration be scheduled for a particular day. The exact calibration interval is then calculated based on that date (example in Figure 4).
Figure 4 Setting the due date for calibration scheduled for a particular day
There are no mandatory requirements with regard to the scope of calibration. Requirements from the pharmacopoeias or widely recognised requirements can be used as a reference point. For example, a balance must be calibrated over the operating range that is used. A photometer used during GMP analyses should meet the requirements of Ph. Eur. 2.2.25. Critical parameters or other lessons learnt during the qualification of the instrument can also be included in the scope of calibration.
The definition of acceptance criteria can be based on general requirements, e.g. from pharmacopoeias, or on the practical application of the instrument. For example, Chapter 2.2.25 of the European Pharmacopoeia contains requirements affecting photometers. On the other hand, a broad acceptance criterion of ±10% can be perfectly acceptable for a 10-µl piston-operated pipette that is used exclusively for pipetting enzymes during enzymatic determination when a fluctuating amount of enzyme does not affect the result.