What Companies Need to Know about GMP Measuring Instrument Calibration
Pharma manufacturing standards tend to be higher than many other sectors, and every process is heavily regulated by the Regulatory Authorities. According to pharmaceutical cGMP (current Good Manufacturing Practice) guidelines, pharma companies need to conduct regular instrument calibration as part of their validation and qualification activities.
What is Calibration and How Is It Different from Adjustment?
Calibration is the process of comparing measurements taken from an instrument under test against a known value or highly accurate standard, to determine the accuracy, reliability and traceability of the former. It is usually conducted under specific conditions (e.g. operating conditions), with procedures that can easily be reproduced.
Adjustment is the process of making changes to a faulty instrument so that it “reads true”, but this can invalidate a previous calibration. In case of any deviations, equipment needs to be re-calibrated after it’s adjusted or aligned, to ensure that incorrect measurements do not affect product quality or production efficiency.
Why is Calibration Important for Measuring Instruments?
The process of measurement is conducted to check whether something is accurate within a set of specified limits. The results are displayed as a numerical value and a standard unit, where the latter is a defined quantity based on a recognised system of metrology, e.g. Fahrenheit, inch, kilogram, bar, ounce, etc.
The standard unit may differ based on the system (metric or imperial, for instance), and devices used for this process include everything from simple gauges and thermometers to complex laser-based measuring systems, electronic weighing scales, etc. All these devices need to function perfectly, which is where calibration comes in.
Measuring instrument calibration helps pharmaceutical companies with Quality Assurance and cGMP compliance, in 3 main ways:
1. Traceability – Measurement results from a certain instrument need to be consistent with similar measurements taken from others, regardless of differences in the location, operators or even the instrument itself. This allows for greater control at any stage of the manufacturing, testing or validation process.
In order for these readings to be related to standard measurements, they need to follow a recognized national or international system of metrology. If a certain machine displays readings in “inches” or “oC”, the value of each “inch” or “oC” should be the same as any other machine using the same metrological system.
2. Accuracy – The accuracy of instrument readings affects the decision-making process for any production stage, and incorrect measurements can lead to quality, safety and compliance issues. Accuracy can be determined through “uncertainty”, a numerical estimate that is used to calculate the quality of any measurement.
This estimate is usually a spread of values that can reasonably be applied to a certain quantity. The stated uncertainty of a measurement allows it to be compared to others and reduces the risk of poor decisions made due to errors in measurement, as well as potential consequences of these decisions.
3. Reliability – As part of the validation programme for pharmaceutical products, the reliability of measuring instruments also needs to be established. Few devices have a higher accuracy than required for common tasks, and the cost, quality or complexity of the instrument rarely have an effect on its reliability.
By calibrating instruments regularly, it’s possible to maximize the reliability of their measurements by locating and correcting faults in time. Adjustments can be made before measurement errors affect the quality of the product, or are discovered during a regulatory inspection/internal audit.
Improving the Traceability of Measurements
According to pharmaceutical cGMP guidelines, companies need to show traceability for any measurement that determines the quality of the finished product. Traceability can be broken down into 3 main elements, which need to be followed during the measurement procedure:
- A definition of how the quantity needs to be measured, based on recognized standards.
- A measuring device that has been properly calibrated as per the manufacturer’s instructions.
- An operator (or operators) properly trained in the use of the measuring device, procedure and standard.
Instrument calibration is an important maintenance requirement that must be performed by any business using measuring devices. Whether you outsource calibration services or choose to perform them in-house, a regular calibration schedule will help reduce risks and improve both quality and performance.
Guest Author Bio: Edward Simpson is a seasoned Calibration and Technical Engineer working for RS Calibration Inc. Edward has a knack for finding faults in machines and does not rest until they are rectified to perfection. He lives in Pleasanton, CA and can be contacted anytime for matters related to machines. He also invites people to visit his company www.rscal.com to learn more about the type of calibration work he does.
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Annex 1 has finally arrived, 25th Aug 2022 saw the publication of Annex 1. Normally, updates to GMP chapters and Annexes have a 6-month lead time for implementation. In the case of the new Annex 1, the lead time is 12 months, except for clause 8.123 relating to lyophilization which has 24 months lead time.
Annex 1 was first issued in 1971 as the only annex in the first ever UK guide to Good Manufacturing Practice. Since then, there have been several updates but not full revisions. In 2012 there was a proposal to revise Annex 1 with a re-proposal in 2014 by the UK’s MHRA. At the time, a full rewrite was considered unlikely and instead the intention was to provide a document that would confirm regulatory expectation and as such, not place any new requirements or costs on the pharmaceutical industry.
While this principle, is still upheld, it was clear from the first draft for public comment of December 2017, that a rewrite was being undertaken. The first draft created around 6200 comments coming from regulatory organizations, such as the pharmaceutical cooperation scheme, regulatory bodies outside of the EU, support organizations such as the Parenteral Drug Association, the Parenteral and Healthcare Sciences Society, the Pharmaceutical Microbiology Interest group as well as representatives from the manufacturers within the pharmaceutical industry to name just a few. Rarely do updates require a second public consultation but in the case of the annex 1 update a second draft was issued in March 2020 although this was a more targeted review in terms of the sections and clauses that comment was being sought for.
About the author
Andy started working in the Pharmaceutical industry in 1985 as a lab technician for Smith & Nephew. Following this he had a number of roles culminating when he took over as QA Microbiology Manager. In 2003 he moved into Pharmaceutical Training and then in 2007 he moved back into Microbiology when he took up the position of Microbiology Manager for Catalent Pharma Solutions. Since 2012 he has operated as a consultant specialising in Microbiology and Quality Systems.
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There are a number of half-day workshops organised to take you through the changes in more detail and to look at how they relate to your organisation.
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