Stability testing, also known as shelf-life assessment, stand as a pivotal stage in the pharmaceutical development, crucial for verifying the identity, potency and purity of ingredients within a formulation.
Pharmaceutical stability is defined as the ability of a specific formulation within its designated container to maintain conformity to its physical and chemical protective standards. In other words, it denotes the product’s capacity to retain its initial properties and attributes throughout the storage within defined parameters. Stability testing serves as a comprehensive assessment of the impact of environmental variables on drug substances or formulated products, facilitating the prediction of shelf life, identification of optimal storage conditions, and formulation of precise labelling instructions. The data derived from stability testing is an important requirement for regulatory approval of drugs and formulations.
To determine the duration for which a pharmaceutical product can be safely stored without any change in its original chemical composition, adherence to the guidelines set forth by the International Council for Harmonisation (ICH) is imperative. The ICH guideline for Stability Testing of New Drug Substances and Products Q1A(R2) outlines procedures for stability testing of new products intended for human use. Addressing both intermediate and long-term storage conditions, the guideline establishes robust stability study protocols. These protocols mandate the comprehensive assessment of physical, chemical, biological, and microbiological attributes utilizing validated stability-indicating methods.
A reliable method to estimate shelf life involves analysing a quantitative attribute, such as the degradation of products. According to the ICH guidelines, we can figure this out by finding the earliest time when we’re 95% sure that the average amount of breakdown hits a certain level. To do this, we need to test at least three batches of the product.
When handling multiple batches, it is required to pool their data if batch-to-batch variation is small. This allows for determination of an overall shelf-life estimate. However, before pooling the data, it’s crucial to assess the batch similarity. We use a statistical test where if the chance of them being different is less than 25%, we consider them similar enough.
The shelf lives for individual batches can be estimated also by using individual intercepts, individual slopes and the pooled mean square error derived from all batches. Subsequently, the shortest estimate among the batches is selected as the retest period or shelf life for all batches.
Shelf-life estimation relies on the utilisation of linear regression models. The flowchart (Fig. 2) demonstrates the process of determining the suitable regression model. For instance, if the batch size is three or more, covariance analysis is performed on the data first to check for interaction effects between batch and time. A statistically significant interaction suggests that the model has common slopes, meaning that the loss rate of the active ingredient is consistent across all batches. After determining the appropriate model, we can find out the shelf life by looking at the time at which the 95% boundary of the model meets the acceptance criterion.
Challenges in Stability Testing
The stability testing of pharmaceutical products typically entails a highly intricate series of procedures, demanding considerable time and financial resources. Additionally, achieving an accurate depiction of a drug or product’s shelf life necessitates a profound understanding of statistics.
Innovative ‘Off-the-Shelf’ Solutions
Statistica’s Stability analysis extension node and Alteryx Designer’s stability analysis tool developed by StatSoft enables users to effortlessly conduct stability analyses. These sophisticated tools guarantee robust and accurate results that comply with established guidelines.
In Statistica, for example, once you choose the relevant variables, executing the Stability node initiates a series of tests, culminating in a comprehensive report, providing all essential elements for thorough stability testing.
Alteryx provides users with three tailored versions of stability studies to suit different needs:
- The app version offers a user-friendly parameter input without launching Designer, the desktop application of Alteryx. Users simply click on the app to input the dataset and its parameters. A comprehensive report is exported to a designated folder.
- The short lightweight Designer version streamlines the process within Alteryx Designer, featuring a compact workflow. Results are conveniently outputted within Designer and saved in a designated folder.
- For Alteryx enthusiasts, the extensive Designer version offers advanced options to tweak parameters, facilitating flexible workflow adaptation. Results are again accessible within Designer and stored in a local folder.
These tools are especially advantageous as they streamline the entire stability testing process, saving valuable time and resources for companies. By automating the calculations and procedures involved in stability testing, including data assumption checks and preprocessing, our tools eliminate the need for manual data entry and complex calculations, reducing the potential for human error and ensuring accuracy and consistency in results.
Moreover, our tools offer a user-friendly interface that requires minimal training to operate, making them accessible to a wide range of professionals within the industry.
Furthermore, the efficiency gained through these tools allows companies to accelerate their product development timelines, bringing new products to the market faster while ensuring compliance with regulatory standards. This not only improves operational efficiency but also enhances competitiveness in the marketplace.
In addition to time savings, our tools provide comprehensive reporting features that enable users to generate detailed analysis and insights from stability testing data. This facilitates informed decision-making and enables proactive measures to be taken to optimize product quality and shelf life.
In closing, the journey towards ensuring pharmaceutical stability and accurate shelf-life estimation demands meticulous attention to details. Leveraging tools such as TIBCO Statistica’s Stability analysis extension node and Alteryx’s stability analysis tool revolutionizes this process, offering streamlined solutions that save valuable time, resources, and mitigate the risk of errors. As we navigate the complexities of pharmaceutical stability testing, embracing innovative solutions becomes paramount, ensuring the delivery of safe, effective, and high-quality products to consumers worldwide.
Contact us if you would like to find out more about the possibilities for stability analyses!
References:
ICH Guidelines for Stability Testing
Research Paper: Linear Regression for Stability Testing
