Even a small error during the manufacture, packing, or storage of a pharmaceutical product can severely impact the health of thousands of patients who consume it. This is the reason why regulatory bodies lay down stringent quality parameters that pharma companies must meet to get their products approved. Measurement of these parameters at different stages in the manufacture of drugs is done using several instruments. Naturally, it follows that the ability of these instruments to provide accurate measurements is critical to the manufacturing process. Assessing this ability is the very purpose of the activity called CALIBRATION.
Definition
Calibration is defined as the process of determining the
accuracy of an instrument. This involves:
(a) Obtaining a particular reading from the instrument under
study.
(b) Comparing this reading with one obtained from a standard
instrument.
(c) Assessing the degree of variation between the two
readings.
(d) Adjusting the instrument so that it gives readings in
keeping with established standards.
Objectives of Calibration
The calibration of an instrument helps to assess its
accuracy. It helps to determine how accurately the instrument is producing
results within the prescribed limits. The main purposes of calibration are:
1. To ensure instrument/equipment readings display correct
readings each time.
2. To determine how accurate, precise, and reliable are the
measurements produced, as well as the degree of deviations that are produced.
3. To check how reliable the instrument is by examining if
it delivers reproducible results.
4. To assess the degree of drift from accuracy over time.
5. To ensure adherence to cGMP guidelines for quality.
When an instrument has to be calibrated, its measurements
are compared with the ones obtained from a standard instrument. Comparison may
also be made against an existing instrument that is known to give measurements
at a level exceeding the prescribed limits of accuracy and precision.
Generally, the accuracy of the standard must be ten times that of the
instrument under test. However, an accuracy ratio of 3:1 is also acceptable by
regulatory authorities.
Significance of Calibration
When instruments and equipment are used regularly, over
time, they tend to undergo some or the other damage. This results in a shift in
the measurement so that the devices are no longer giving accurate and precise
results over the expected range. By measuring the accuracy, precision, and
range of such devices, calibration helps to track the shifts and the data
generated can be used to rectify the functioning of the instrument.
Sometimes, ambient conditions such as humidity, temperature,
and pressure may cause a drift in the measurements made by instruments.
Calibrating such instruments at regular intervals can help to ensure the drift
does not exceed acceptable limits.
Thus, regular calibration of equipment and instruments makes
it possible to guarantee that they continue to function without any error, and
in turn, this ensures reproducible pharmaceutical quality of the products.
When calibration is not done for a long time, it may lead
to:
• Faulty measurements and discrepancies that impact final
product quality.
• Deterioration of drug materials leading to a safety threat
to those consuming the product.
• Waste of resources and time.
• Loss of time because of faulty process which has to be
shut down and re-started after calibration.
• Product recall because of damaged drug products.
Frequency of Calibration
The frequency of instrument calibration depends on the
nature of its variation or drift from accuracy over time. It also depends on
how important that particular instrument’s measurement is to determine the
quality of the end product. It is therefore important to set up a calibration
schedule for each instrument such as weekly, monthly, bi-monthly, quarterly,
half-yearly, or annually. Generally, instruments need to be calibrated in the
following situations:
1. As soon as it is installed before it is used for the
first time.
2. Both before and after taking any measurement that is
critical to product quality.
3. When anything out of the ordinary occurs – for example, a
fall, bump, or electrical shock is generated.
4. When readings appear suspect in accuracy.
5. After any repair work has been done on the instrument.
6. As part of the routine calibration schedule.
7. At all those times recommended by the instrument
manufacturer.
Calibration Methods
Instruments can be calibrated in several different ways. The
method chosen generally depends on what results one desires from the
calibration exercise and also on particular regulatory requirements that are to
be met. The three common procedures used for calibration include - Standard
Calibration, ISO 17025 Accredited Calibration, and Calibration with Data.
Calibration plays a vital role in controlling the
uncertainty around process measurements. Regular calibration can reduce errors,
improve the accuracy of instruments, and make it easier to ensure good quality
of the final product. Thus, pharmaceutical companies need to have a calibration
schedule that will give them confidence in their process measurement and
control.