The pharmaceutical industry is driven by the need for safe and effective products that are of the desired quality. Quality assurance is a concept that emphasizes building quality into products. For this to be achieved, all components that are part of the manufacturing and testing process must perform as expected, and provide results that are accurate, precise, and reliable. Measuring instruments and other equipment and tools used at different stages must therefore be capable of providing accurate data. Any change in their performance characteristics may lead to costly errors that may even pose a danger to life. Calibration and validation are two aspects that help to avoid such errors and ensure a quality product reaches the patient.
Even a small error during the manufacture or packing or storage of a pharmaceutical product can have a severe impact on 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.
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. A 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 of 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 the 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 the 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 inaccuracy.
5. After any repair work has been done on the instrument.
6. As part of a routine calibration schedule.
7. At all those times recommended by the instrument manufacturer.
Instruments can be calibrated in several different ways. The method is chosen generally depends on what results in one desire 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.
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