External factors are also taken into consideration when performing a Stability Study, as these might have an effect on the product. Such external factors are light, heat, humidity, temperature, etc. The Stability Study performed will show what effect these factors might have on the product and determine the most ideal storage conditions, shelf life and packaging. In order to perform a Stability Study, it is required that the company follow the ICH Quality Guidelines on Stability Studies Q1A (R2).
These guidelines provide a very detailed overview of what is required when carrying out a Stability Study, including time points, analytical requirements, evaluation of analytical data obtained, specifications, etc. Over an extended period of time, or if the product is exposed to extreme storage conditions, its physical, chemical and microbiological properties might be compromised. This is the main reason for performing stability studies, in order to ensure that the product’s quality is maintained throughout its shelf life. Prior to starting a stability study, an adequate testing program must be written.
This program is created to ensure that all the stability characteristics of the product remain stable throughout their labelled expiry dates. Within this program, the sample size (at least three primary batches) must be written, along with the testing intervals which will be applied. The batches chosen for the study must maintain the same formulation and must utilize the same container closure system (packaging).
It is very important that during the stability studies, time points are also adhered to, i.e., if the product is to be sampled and tested during the nine-month interval this deadline is met. The storage conditions and references to the validated methods should be included in the protocol/program. All records of testing activities are to be adequately archived in case they need to be reviewed by an authority.
Stability monitoring and testing can be carried out in three ways; it is done by checking the product’s physical, chemical and microbial characteristics. Physical checks include changes in the product’s appearance, water retention, dissolution properties, disintegration properties, changes in its pH and changes in the viscosity of the product (more testing can be included as necessary). Chemical checks include the determination of any degradation impurities through the related substances analysis and also the assay content.
Microbial checks primarily identify the presence of any pathogenic microorganisms. In cases where the product comes with an applicator, such as an inhaler, the functionality is also assessed. The data used in the Stability Study needs to be quantitative. Two of the main types of Stability Studies performed are Real-Time Stability Testing and Accelerated Stability Testing.
Real-Time Stability Studies are done on products which are stored according to their recommended conditions on the outer packaging. Continuous checks are performed on the product in order to confirm if the product is still within specification or not. Such checks are performed until the product fails; once it is not compliant with the specification then the shelf life can be determined.
According to the ICH guidelines the product is to be tested four times in the first year, at three-month intervals (at three, six, nine and twelve months). After the first year is concluded it is to be tested twice the following year at six-month intervals and then it is to be tested once every year until a failure result is obtained. Once a failure result is obtained, no more testing is carried out and the data obtained is evaluated to determine what the shelf-life of the product will be.
An Accelerated Stability Study occurs when the targeted product is stored in exaggerated conditions, such as where factors such as temperature and humidity are accelerated. This is done to establish the worst-case scenario for the product. Stability chambers are used as they can be temperature and humidity controlled; if there are a larger number of products on stability the company can also invest in a walk-in stability room, which can also be precisely controlled and maintained at the desired set points.
It is essential that the stability chamber is qualified and well maintained. Its temperature and humidity levels are also to be regularly monitored with data loggers and alarm notifications must be sent to designated people when there are excursions in order to ensure that the required conditions are being applied to the product.
The testing timeframe should be a minimum of six months at the accelerated conditions. If for example, a product which is being kept within the conditions of 40°C/75% RH remains stable up to six months, it can be given a shelf life of up to 24 months. The aim of an accelerated stability study is to determine the time of degradation of the product.
Therefore, based on the information obtained from the study, the storage conditions can be determined. Accelerated stability studies are also very useful in cases of temperature excursions, i.e., if there is a temperature excursion during transport, when the product was exposed to a temperature of 40°C, the stability data can be checked to see if the product quality was compromised by this temperature for the time it was exposed.
Prior to closing a stability study, it is essential that the results are trended. When the results are trended, a clear picture is given to the reviewer on the overall results obtained throughout the study. In this way, during the analytical data review, one can easily identify any abnormal trends within the extracted data.
Performing stability studies will confirm that a shelf life is adequately determined, appropriate storage conditions are ensured based on the properties of the product, and the study will aid in further product development. It is also important to have stability studies on products which are currently on the market (retained samples studies) to ensure continuous monitoring for efficacy and integrity of the product. Above all, the most important aspect is that product quality is maintained.
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PQE Group can support all of these inter-related services and requirements, for both regulated and non-regulated markets, through our federated partner, Quintian Pharma, which is committed to providing services and support to the pharmaceutical industry, following all EU directives on new products.
