What is Stability Testing :
Stability testing is the process by which pharmaceutical manufacturers observe their product over predetermined lengths of time in specific environmental conditions to determine if there is any change in the quality of the Active Pharmaceutical Ingredient (API) or Final Product (FP). When manufacturing pharmaceuticals and other FDA-regulated products, there are numerous factors that must be tested before the product is approved and released to the public for consumption. Pharmaceutical manufacturers must take great care to observe the influence of various environmental factors such as light, temperature, and humidity on their product.
Why is pharmaceutical stability testing is Important :
Pharmaceutical stability testing is important for determining factors such as a product’s shelf life, optimal storage conditions, retest period, and assuring its overall quality for consumers. During a pharmaceutical stability test, manufacturers observe their product for any changes in the physical, chemical, biological, and microbiological makeup of the substance. All of these elements may impact the safety and efficacy of the product for the consumer, so it is vital to conduct extensive testing before putting a drug on the market.
Who determine the Guideline for stability testing of Pharmaceutical Products :
The stability testing guidelines are set by the International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use (ICH). Formed in 1990, the ICH is comprised of regulatory authorities and pharmaceutical professionals for the purpose of discussing scientific and technical aspects of drug registration. As stated on their website, the mission of the ICH is to “achieve greater harmonisation worldwide to ensure that safe, effective, and high quality medicines are developed and registered in the most resource-efficient manner.”
What are the ICH Guidelines for Stability studies :
The ICH sets criteria for stability testing based on three different types of studies: long term studies (also referred to as real time), intermediate studies, and accelerated studies. These studies are conducted for different durations of time and are intended to measure a product’s condition at several different stages, such as the length of its proposed shelf life or how it reacts during short-term conditions (e.g. in transport).
The ICH guidelines for the three types of stability studies are as follows:
|Study||Storage Condition||Minimum time period covered by data at condition|
|Long Term||25°C ± 2°C/60% RH ± 5% RH|
30°C ± 2°C/65% RH ± 5% RH
|Intermediate||30°C ± 2°C/65% RH ± 5% RH||6 months|
|Accelerated||40°C ± 2°C/75% RH ± 5% RH||6 months|
* It is important to note that it is up to conductor’s of the stability study to decide the storage condition for the long term stability testing and if 30°C 2°C/35% RH 5% RH is the long term condition, no intermediate testing is required.
In addition to varying the duration of the stability study, the ICH also sets guidelines for stability studies based on the five climatic zones of the world. The ICH guidelines for stability studies are intended to simulate different climatic conditions to ensure a pharmaceutical product’s efficacy and integrity across all regions of the planet.
The following table describes the climatic zones and the recommended long term stability testing conditions:
|Zone||Description||Long Term Stability Testing Condition|
|Zone lll||Hot-Dry Zone||30°C/35%RH|
|Zone lV a||Hot-Humid/Tropical Zone||30°C/65%RH|
|Zone lV b||Hot/Higher Humidity Zone||30°C/75%RH|
What is Long term Stability Testing :
Long term, or real time, stability testing programs subject products to recommended storage conditions and normally utilize a longer monitoring period for degradation to establish product shelf-life. This long term stability testing procedure differs in comparison to accelerated shelf life testing, which instead exposes products to elevated storage environments. The drug product is monitored under specified storage conditions until it no longer exhibits the expected quality standards. Long term stability testing typically lasts a minimum of 12 months, but may extend beyond that up to product shelf life plus 1 year.
Why you need Long term Stability testing for Drug Substances :
Long term stability testing is essential for determining the shelf life and storage periods of products under their expected environmental conditions. It provides manufactures and consumers insight as to when products will stop performing as intended. Even if the stability properties of an API are thought to be fully understood, long term stability testing may be utilized if there is a change in packaging or the formulation of the product has been altered.
What are Accelerated stability Studies :
In accelerated stability studies, pharmaceutical products are held at exaggerated stress conditions for a period of six months. The elevated conditions are meant to accelerate the rate of decomposition in the product. Conducting accelerated stability studies allows pharmaceutical professionals to then draw conclusions about the shelf life of the product. For instance, if a product holds stable at 40℃/75% RH for the duration of the six-month accelerated study, it can be assigned a shelf life of 24 months. Successful accelerated stability studies can expedite the process of getting a drug on the market, but full approval must be backed by “real-time” data.
What are Intermediate stability Studies :
Intermediate stability studies are not always required, but they may be used if a significant change has occurred to the product at any point during accelerated testing. Intermediate studies are designed to moderately increase the rate of chemical degradation or physical changes for a drug substance or drug product.
How is a Stability Study Conducted :
A stability study is composed of many different tests and involves the careful handling and pulling of samples to precisely record their condition at various points in the study. The ICH recommends collecting stability data for at least three batches of product representative of the final quality of product that will be made to production scale.
Criteria for evaluation during a stability study may include tests for:
- Changes in PH
- Moisture content
- Microbial activity
To store these samples at the designated condition for the duration of the study, Temperature controlled Humidity Chambers and walk-in stability rooms are utilized to precisely control and maintain the desired set point. Failure to maintain the required condition for a stability study may mean a loss of several months or years of work, so it is of high importance to ensure that the equipment is built to exact specifications and will consistently hold the needed temperature and humidity levels.