64 BIOTECHNOLOGY
The IMPORTANCE of STABILITY TESTING
Naomi Dunning- Foreman explains why stability testing is an essential step on the path to drug development
C linical trials are
understandably a critical and well-known part of
the drug discovery, development and approval process, with results often featured in the media. Given the importance of drug safety, it is not surprising that there are a number of additional testing processes for the assessment of drug safety and efficacy. Although these tests are not as publicised as clinical trials, they are still very important. Stability testing is one such example.
An important step in the
drug approval process, stability testing assesses how the quality of a drug substance or drug product (including its packaging) varies with time under the influence of
environmental factors, including temperature, humidity and light. Te process determines whether any physical, chemical or microbiological changes affect the efficiency and integrity of the final product, thereby ensuring that a pharmaceutical product is safe and effective, irrespective of where in the world it will be supplied. Moreover, stability testing establishes the shelf life and recommended storage conditions of a finished pharmaceutical product and the retest periods for a drug substance.
Comprised of two
stages (stability storage and downstream analytical testing), stability testing ensures compliance with international regulations that form part of the registration process for a new drug substance or drug product. For the purpose of stability testing, the International Conference on Harmonisation (ICH) divides the world into five climatic zones based on a combination of temperature and relative humidity (RH). Tis division ensures that the
Table 1. Long-term (stability) testing conditions Climatic Zone
Zone I
Zone II Zone III Zone IV Zone IVb Refrigerated Frozen
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differences in climatic conditions in the varying regions of the world are considered for stability studies. Te climatic data that defines these different regions is related to the Mean Kinetic Temperature (MKT), which is a widely used measure in the pharmaceutical industry to express the overall effect of temperature fluctuations during storage or transit. Te five climatic zones are
replicated in long-term stability studies to simulate the conditions worldwide that a drug substance or drug product is subjected to. Te ICH presents guidelines on the conditions that should be included in a stability study, which are often referred to as ICH conditions. Te long-term testing conditions are shown in Table 1. During stability testing, a
drug substance or drug product is evaluated under the relevant ICH storage conditions, testing its thermal stability and its sensitivity to moisture. Te storage conditions tested and the lengths of the studies chosen must cover the storage, shipment
and use of the product. For example, if a drug is produced in the UK (Zone I) and shipped to Egypt (Zone IV) for distribution via Europe (Zones I and II), it would need to be tested under zones I, II and IV. Troughout the duration of the study, the stability of the drug is established through physical, chemical, biological and microbiological tests. An example of these tests is stress testing, of which photostability testing is a specific case that assesses the effects of light exposure on the drug product or substance. A shelf life and label storage instructions are then determined from the results of the tests.
Temperatures
21°C (± 2°C) 25°C (± 2°C) 30°C (± 2°C) 30°C (± 2°C) 30°C (± 2°C) 5°C (± 3°C) -15°C (± 5°C)
Humidity
45% RH (± 5%) 60% RH (± 5%) 35% RH (± 5%) 65% RH (± 5%) 75% RH (± 5%) None None
Outsourcing stability testing Stability testing can be carried out in-house or by dedicated service providers. Source BioScience provides outsourced stability storage services to many global pharmaceutical companies. In addition, the company offers complementary analytical testing services at its facility in Stirling, UK. Due to increasing demand, the company is currently in the process of expanding its analytical testing capabilities to offer these services from a second site in Rochdale, UK, with further plans to expand into Europe and the USA. With the facilities and expertise to support clients through the entire stability testing and batch release process, Source BioScience provides a full range of tailored solutions to the pharmaceutical industry, which also includes clinical trial support. In addition to serving the pharmaceutical industry, the
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