Expanding an Analytical Framework

January 4, 2023 / by John Long, Ph.D.

Increased expectations, increased accountability

Rapid evolution. In short, that’s what we’re seeing in the method development and assay life cycle field. The concepts have been around for quite some time, but now with updated and new guidance for analytical life cycle and analytical method development, we’re seeing a more dynamic period emerging in the space. This includes increased expectations for analytical method development and increased accountability for reporting development data.

A while back, I spoke at a conference on analytical procedures in Philadelphia and gave two presentations:

• Key Elements for Analytical Procedure Life Cycle Management Success - Insight from the Front Line, and
• Setting Phase Appropriate Acceptance Criteria for Qualification and Validation.

The conference was co-sponsored by KENX and Temple University. While there, I had the benefit of discussing these enhanced approaches with USP and FDA representatives who helped develop three guidance documents regarding analytical procedures, and learn more about their intentions and expectations. These documents regarding analytical procedures from USP and the International Council for Harmonisation (ICH) are:

• USP <1220> Analytical Procedure Life Cycle, (effective May 1, 2022)
• Validation of Analytical Procedures, ICH Q2(R2) (Draft guidance, released March 24, 2022)
• Analytical Procedure Development, ICH Q14 (Draft guidance, released March 24, 2022)

These approaches are designed to improve regulatory communication, facilitating more efficient, scientifically sound, risk-based approval processes, as well as post-approval change management of analytical procedures. This recommended method development process includes:

• Evaluation of sample properties
• Defining the Analytical Target Profile (ATP)
• Conducting risk assessment and evaluating prior knowledge
• Conducting multi-variate experiments
• Defining an analytical procedure control strategy
• Defining a life cycle change management plan

During my presentations, I discussed those topics and shared how Aldevron has integrated the concepts of method development and assay life cycle into its processes, and approaches to consider.

ATP and control strategy are key
As part of this enhanced approach to method development, the ATP is a key enabler. ATP is an initial assessment of the type of method needed and the required parameters, such as level of precision and accuracy. This becomes the basis for the control strategy and validation study design. Analytical control strategy is based on development data, particularly from range-finding and multivariate analyses, and is an important component of the overall manufacturing and testing strategy to ensure product quality and patient safety.

Key elements to the control strategy, such as in-process testing strategy and critical reagents, are based primarily on data rather than historical knowledge. With the enhanced guidance, we can now take a systematic approach to method development, rather than one that’s largely empirical. Development steps include:

• ATP
• Proof of concept
• Range finding
• Estimate of precision and sources of variance
• Accuracy assessment and sources of bias
• Robustness
• Sample hold times
• Evaluation of stability indicating capabilities
• Identification of impurities

Special considerations for platform methods need to be considered as well. For a CDMO, there are multiple client products in our system at a given time. Wherever we can develop single methods that are able to test multiple product types, this is of great benefit to throughput for our clients.

Analytical method development is still an evolving and challenging activity, but these guidelines can allow us to increase throughput and minimize rework. By right-sizing the approaches to the specific phases of the analytical method life cycle, we can make the most of available resources while maintaining high quality.

• Want to learn more? Contact John Long with your questions
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