What is calibration?
Within the pharmaceutical industry, analytical instruments are used for specific analysis of drug substances (DS) and / or drug products (DP). Calibration can be explained as a process by which the correct performance of an instrument is ensured. It should not be mixed with the system suitability test (SST), which is performed each time the method is done. The performance of an instrument may vary because of multitude of reasons such as fluctuations in the environment or its ageing components.
Differences in performance may also be seen during servicing of the instrument or replacement of its components. During calibration the performance of the instrument is checked using reference material and in case a deviation is noticed the instrument is adjusted to the correct value. For a laboratory to ensure quality system, it is mandatory to minimize these variations and hence a periodical calibration procedure is applied. For this, the periods may vary from daily (like pH meters) to monthly (e.g. balances every 3-6 month) or yearly (e.g. photometers), depending on how often the instrument is used and which criticality the instrument is assigned to.
Traditionally, there are two existing concepts for calibration processes that laboratories can choose from:
- All instruments and equipment are calibrated.
- The calibration procedure is applied only to instruments capable of physical measurements, and where the output is a direct measurement of a traceable physical parameter. For example, balances, spectrometers, thermometers, etc. may be calibrated because there are standards available to determine the uncertainty of the measurements. For others, only performance verification can be performed in the laboratory. For example, for an HPLC system, the performance is maintained within a set of predetermined criteria to ensure the quality and consistency of the generated data. Typical features include injector precision, flow rate accuracy, gradient accuracy, detector response, etc.
Calibration is an integral part of the quality system and is required to follow according to a previously defined Standard Operating Procedure (SOP).
A very simple example is the daily calibration of a pH meter, where the pH of two reference standard solutions (e.g. pH 4 and 9) is measured, small differences in the obtained values are observed and then the machine is accordingly adjusted to show 4 or 9 as true values.