ICH Q14 Implementation: Expert Panel Discussion on Analytical Method Development

This summary accompanies a recent expert forum discussion organised by BioQC, and we appreciate the panellists for their time and expertise.

An expert panel featuring industry leaders and academics gathered to discuss practical implementation of the ICH Q14 guideline for analytical procedure development. The discussion addressed common misconceptions, shared diverse organisational perspectives, and provided practical guidance on adopting enhanced approaches for analytical method development in biopharmaceutical settings.

ICH Q14: Evolution Not Revolution

A central theme emerged that ICH Q14 formalises good scientific practices many organisations were already applying informally. Industry has been conducting risk assessments and systematic method development for decades, but this knowledge often remained undocumented in the minds of subject matter experts. The guideline provides visibility, rationalisation, and clear definitions that align the industry whilst creating pathways for regulatory communication about lifecycle management.

However, perspectives varied. Whilst experienced pharmaceutical companies recognised familiar concepts now formalised on paper, biopharma organisations, particularly those with scientists from biomedical rather than analytical backgrounds, welcomed the guideline as essential documentation

of design thinking approaches. For these groups, ICH Q14 provides concrete guidance for creating robust methods that work reliably in routine operations, filling a gap where experimental execution was taught but not analytical method design principles.

The Continuum: Not One Size Fits All

The panel emphasised that the minimal and enhanced approaches represent a continuum rather than binary choices. Organisations should select elements based on method complexity, risk, and prior knowledge. For well-established technologies used for decades in both academia and industry, minimal approaches suffice. For complex methods with high variability, such as cell-based potency assays with numerous variability sources from dilution steps, cell culturing, and readout processes, enhanced approaches provide clear advantages through systematic risk assessment and factor identification.

The concept of modular implementation emerged: organisations can selectively apply enhanced approach elements where they add value. Not every method requires full Method Operable Design Region (MODR) studies. The analytical target profile benefits all methods, but complete deployment of every Q14 element may be excessive for straightforward procedures. For capillary electrophoresis methods, investing in thorough risk assessment and design of experiments for robustness may provide more value than developing a full MODR.

Multivariate Optimisation: Tool Not Replacement

Multivariate optimisation is not about pushing buttons but starts with properly defining the analytical target profile to rationalise factor and response selection. ICH Q14’s emphasis on risk assessment addresses a gap where developers often rely on experience and informal knowledge rather than systematic evaluation. Screening designs can inform the risk assessment step, identifying critical method parameters from initial fishbone diagrams. Response surface designs then enable detailed study of these parameters and definition of the Method Operable Design Region.

The panel agreed that multivariate development data can inform validation, particularly for robustness. ICH Q2 revision acknowledges that suitable development data can contribute to demonstrating validation, eliminating redundant robustness experiments under validation protocols when adequate datasets already demonstrate parameter robustness. However, the science must drive the approach. Multivariate methods reveal factor interactions and enable uncertainty propagation throughout the experimental domain but cannot replace fundamental understanding of the analytical system.

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