Naomi Dunning-Foreman explains why stability testing is an essential step on the path to drug development
Clinical 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. The 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). This division ensures that the differences in climatic conditions in the varying regions of the world are considered for stability studies. Zone I is defined as temperate, zone II as Mediterranean/subtropical, zone III as hot/dry, and zone IV as hot/humid. In addition, a zone IVb was introduced relatively recently, which is defined as hot/higher humidity and represents ASEAN (Association of Southeast Asian Nations) testing conditions. The climatic data that defines these 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.
The 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. The ICH presents guidelines on the conditions that should be included in a stability study, which are often referred to as ICH conditions. The 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. The 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. Throughout 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.
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, Source BioScience 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, Source BioScience offers outsourced storage for a number of other clients, including those from life science research, medical, food, cosmetics, chemical/industrial and heritage conservation industries.
Due to the company’s position as both equipment manufacturer and service provider, it offers customers access to standard ICH storage facilities, as well as flexible storage conditions, customised to the client’s needs. There are a wide range of storage conditions available, including low and ultra-low temperature, ICH, non-standard, and photostability, all supported by numerous industry accreditations.
Source BioScience also manufactures equipment for purchase, including stability storage rooms, walk-in rooms, reach-in rooms, environmental storage cabinets, laboratory refrigerators and freezers, laboratory incubators and photostability cabinets. As manufacturers of the equipment it uses, the company consistently develops innovative storage solutions for its customers. Earlier this year, for example, it launched the Polar Series of -70 °C walk-in chambers, which includes the Polar 50, the first -70 °C walk-in chamber.
Stability testing is an important part of the drug development and approval process, determining the safety and integrity of the drug and also its shelf life and storage conditions. Pharmaceutical companies therefore invest significant time and effort into stability testing, either in-house or supported by service companies. With an extensive portfolio of products and services, Source BioScience has the equipment and expertise to support clients throughout the stability testing process and beyond.
Table 1. Long-term (stability) testing conditions
Climatic Zone Temperatures Humidity
Zone I 21 °C (± 2 °C) 45% RH (± 5%)
Zone II 25 °C (± 2 °C) 60% RH (± 5%)
Zone III 30 °C (± 2 °C) 35% RH (± 5%)
Zone IV 30 °C (± 2 °C) 65% RH (± 5%)
Zone IVb 30 °C (± 2 °C) 75% RH (± 5%)
Refrigerated 5 °C (± 3 °C) None
Frozen -15 °C (± 5 °C) None
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Naomi Dunning-Foreman is with Source BioScience.