ICH Stability Testing and appropriate validation of analytical procedures

Regardless of whether you’re at the pharmaceutical manufacturing stage, the biotechnology research and development stage, or the drug discovery lead generation stage of the drug candidate lifecycle, ICH guidelines play a powerful role in guaranteeing the safety, efficacy and quality of those candidates that make it to the shelves.

As regulatory agencies work to implement the ICH Q2 (R2) this year, it is a perfect time to emphasise the importance of appropriate validation of analytical procedures related to stability testing.

The International Council for Harmonisations of Technical Requirements for Pharmaceuticals for Human Use (ICH) protocols were designed through collaboration among regulatory authorities and pharmaceutical experts across the globe. They represent a consensus on the best practices for ensuring standardised testing methods where possible.

In the rapidly evolving landscape of drug candidates, novel and innovative pharmaceuticals often require the development of bespoke and custom testing methodologies. In these cases, adherence to ICH protocols remains a regulatory requirement to ensure robust and reliable stability data.

As an experienced contract analytical testing provider, HMR Labs has over 35 years of experience handling and developing a variety of stability procedures.

Here’s what to consider when managing stability testing, validation studies and stability storage against the ICH guidelines.

New revisions for ICH stability testing 

In late 2023, the ICH Q2 (R1) was replaced by the updated ICH Q2 (R2), reflecting modernisation efforts to align with contemporary technologies and processes. These guidelines are crucial for establishing, submitting, and maintaining evidence that demonstrates the suitability of an analytical procedure, for its intended testing purpose.

In regards to stability, it is familiar to those in the sector, that we’re referring to a drug candidate remaining of high quality, safe for consumption and that the API is of high efficacy for the duration of its shelf life.

The ICH guidelines play a pivotal role in addressing stability testing, a crucial stage that not only determines the shelf life but also appropriate storage conditions and requirements for batch release approval.

But how can the ICH guidelines control the quality assurance of stability testing when the test methodology has been shaped to meet the requirements of the novel drug? This is where ICH stability guidelines come in.

Method development in line with ICH stability protocols

The design and planning of a stability study should always adhere to the requirements of the ICH Q1A – F. Key parameters that any developed method should be evaluated for during validation are outlined in the ICH Q2 (R2). These include:

• Specificity
• Accuracy
• Precision
• Lineraty
• and more

These guidelines ensure that the devised stability studies and the validated, stability-indicating testing methods will generate the data required to determine the shelf life of a new drug product with precision.

As well as shelf-life determination, a robust ICH stability testing method can help provide further insights on product formulation development, improve the likelihood of batch release, anticipate future storage and packaging requirements, and more.

This is why any developed method must align with ICH protocols, as the data it yields is a representation of the pharmaceutical’s safety in accordance with the best practices of pharmaceutical testing in Japan, Europe, US and many other countries.

So, what are the risks and challenges that manufacturers and organisations may encounter that could undermine their compliance with ICH stability guidelines during method development?

Improper stability method development and validation

The first concern with stability testing methods that are not developed and validated to conform with ICH protocols is the potential for inaccurate safety, quality and efficacy data.

Ultimately, this could result in an incorrect determination of a product’s stability, leading to overly conservative or optimistic shelf life and storage conditions.  This risk can result in product deterioration and potentially jeopardise individual patient safety and public health.

Improper method development can be a result of a variety of factors, most commonly including:

Inadequate stress testing

Inadequate method development for your drug compounds has likely not considered all relevant stress factors, resulting in an incomplete evaluation of potential degradation pathways. Stress factors include:

• Temperature
• Humidity
• Light
• Oxidation

A lack of knowledge about the drug product behaviours under stress conditions hinders the selection of appropriate stressors, leading to an improper assessment of stability.

Lack of specificity

Specificity refers to the method’s ability to determine the presence of an analyte without interference from the matrix of other compounds that exist within the test sample. A method that is not specific or fails to accurately measure the drug substance separately from impurities, degradation products or other compounds present will immediately raise concerns over the reliability and accuracy of stability data.

A lack of specificity can result from a variety of factors, from ineffective method development procedures to inaccurate method transfer.

Inadequate robustness testing

A robust testing method is both consistent and reliable, obtaining results that remain unaffected when faced with minor variations in analytical conditions. Inadequate testing can result in less reliable methods that are subsequently sensitive to such variations.

This could take the form of inadequate evaluation of the day-to-day variations expected during routine use, such as the reagents or equipment used, as well as studies to fully understand the effects of deliberate changes in method parameters, such as the mobile phase composition, pH, column temperature, flow rate and more.

Inaccurate method transfer

Accurate and concise method transfer is essential when moving an analytical method from its development or validation phase to its testing facility. This ensures that stability is assessed with a high degree of precision and accuracy. Nevertheless, inaccurate method transfer remains a significant concern for compliant analytical testing.

Inaccurate method transfer can lead to inconsistencies in results between the transferring and receiving laboratories, leading to a potential impact on the reliability and validity of the collected data. In an environment where data quality is vital, this poses a significant issue.

To maintain data consistency and stability data reliability, it is vital to establish comprehensive and well-documented procedures for method validation and transfer. A successful method transfer must ensure that the transferred procedure is being effectively and consistently applied in a different laboratory setting. This requires that the receiving laboratory possesses the necessary training as well as having the appropriate instrumentation to generate equivalent and reliable test results.  

ICH stability testing services with HMR Labs

HMR Labs offers a valuable outsourced solution for your ICH stability development needs. We understand the intricacies of stability testing, enabling us to serve as a valued ICH stability partner through our protocol consultancy and stability study design capabilities.

With access to state-of-the-art stability storage, coupled with our advanced testing equipment housed within our GMP-accredited laboratory, we can conduct your ICH stability testing with ease. We customise our methods development process to align meticulously with the ICH stability guidelines, ensuring high precision and compliance.

Gain the confidence you need with your ICH stability study protocol development, and get in touch with HMR Labs.