The International Council for Harmonisation (ICH) released a draft of the new ICH Q14 Guideline last March. This is the first guideline on analytical procedure development and it’s generating a lot of interest since it can help achieve more robust analytical processes. Along with the revised ICH Q2(R2) Guideline on Validation of Analytical Procedures, these guidelines will represent the scientific and technical standards for analytical methods.

Both the new ICH Q14 and the revised ICH Q2(R2) guideline now wait for public consultation and the final documents are expected to be issued in May 2023. In this blog post we’ll focus on the ICH Q14 guideline, its benefits, and its key implementation aspects. Interested? Keep reading!

Traditional vs. Enhanced approach

The new ICH Q14 guideline introduces the concepts of traditional (also known as minimal) and enhanced approach. It states that “when developing an analytical procedure, a minimal approach or elements of an enhanced approach can be applied.”

This means that regulatory entities don’t require you to follow this enhanced approach. However, you can greatly benefit from it as you will see next.

A traditional approach is defined by a one-time method validation to demonstrate fitness for use. This is done by following a Quality by testing (QbT) approach. One of the shortcomings of this approach is the reliance of assessing method performance mainly during well controlled validation exercises, and this limits the knowledge of the actual performance at the time of testing.

On the other side, in the enhanced approach the analytical procedure is well understood and fit for intended purpose, following a Quality by design (QbD) approach. This approach brings a systematic way of developing and refining knowledge of an analytical method. The generated knowledge is an advantage when it comes to post-approval changes in methods, allowing more regulatory flexibility. Furthermore, this approach enables an improved control strategy, with appropriate set-points and/or ranges for relevant Analytical Procedure Parameters (APPs).

Besides the benefits mentioned above, this approach also facilitates continual improvement by using more analytical procedure knowledge and reduces the amount of effort across the analytical procedure lifecycle.

At this point, we’re sure you’re already in favor of an enhanced approach! So, it’s time to go through its key implementation aspects. In this blog post we’ll focus on the following ones:

  • Analytical Target Profile (ATP), Technology Selection and Risk Assessment
  • Method Operational Design Regions (MODRs) and Analytical Control Strategy
  • Method Lifecycle Management

Analytical Target Profile (ATP), Technology Selection and Risk Assessment

Similar to the Quality Target Product Profile (QTPP) that defines Quality Attributes (QAs), the ATP defines the Analytical Procedure Attributes (APAs) and acceptance criteria for method validation (as per ICH Q2). The ICH Q14 indicates that this tool can facilitate regulatory acceptance of the chosen method. It does this by establishing the intended purpose, the product attributes to be measured and relevant performance requirements for a single attribute or a set of quality attributes.

Furthermore, the guideline also states that ATP guides the technology selection by evaluating which available technologies meet the ATP. This selection is also influenced by internal and/or external prior knowledge, including best practices, state-of-the-art and regulatory requirements, and by business drivers such as operational requirements and technical requirements (availability, cost, etc).

Risk assessments can help you define this ATP and the technology selection. How? By performing risk assessments you can easily identify ATP requirements and business drivers. Additionally, you can score the potential methods against the defined criteria.

Finally, risk assessments can also evaluate the impact of APPs in method performance and prioritise these APPs for DoE/MODR definition. It’s also important to highlight that you should implement risk management at all stages of the procedure’s lifecycle. This way you’ll ensure that the method is in control and meets the ATP criteria.

Method Operational Design Regions (MODRs) and Analytical Control Strategy

According to the ICH Q14 , in this approach, the ranges for the relevant APPs and their interactions can be investigated in multi-variate experiments (DoE).  Using these studies, you can define MODRs. These MODRs consist of a combination of method parameter ranges that meet the criteria for both the ATP requirements and the method performance. MODRs can mean a great competitive advantage because, once approved, you can move within an established parameter range without the need to notify the regulatory agency.

The next step is to, based on both DoE and MODRs, complete the risk assessment process to establish the Analytical Control Strategy. This strategy includes the System Suitability Test (SST), to ensure that the complete analytical system is suitable for the intended application and the definition of established conditions (ECs) for an analytical procedure. Additionally, it includes a list of controls for Change Management Protocols (CMPs), to ensure adherence to desired operating conditions.

Finally, you should review this Analytical Control Strategy over the lifecycle to aim at its continuous improvement.

Method Lifecycle Management

It’s possible that, throughout the product lifecycle, analytical procedures changes can occur. These changes can involve modification of existing procedures or even an introduction of a new technology. Thus, you need to assess the changes and their impact and, according to the ICH Q14 guideline, the tools, and enablers of ICH Q12 are applicable to analytical procedures.

Therefore, an approved post-approval change management protocol (PACMP) and product lifecycle change management plan (PCLM) can be implemented in this approach to ensure that future changes will be acceptable. This is another important advantage of following an enhanced approach, since you need to report all changes in the traditional one.

Accelerate your implementation of the ICH Q14 guideline with Digital QRM

From the ICH Q14 guideline, it’s easy to conclude that risk management plays an important role in the success of the development of an analytical method and its validation.

Implementing a digital QRM can help you define the ATP and select the technology more easily. This way, it allows you to collect the benefits of the enhanced approach faster. Additionally, it can also optimise the risk management over the procedure’s lifecycle and help you determine the required control strategies.

Want to know more about ICH Q14?

Interested in the new ICH Q14 guideline and AQbD? If so, we think you’ll enjoy reading our blog post: Is Analytical QbD the future of Method Development?