Some of the main changes in ICHQ2(R2) include:

• Suitable data derived from development studies (see ICH Q14) can be used as part of validation data.
• When an established platform analytical procedure is used for a new purpose, reduced validation testing is possible, when scientifically justified.
• Some definitions have been amended to be more aligned with biological and non-linear analytical procedures as for linearity → Reportable range. (Such as potency assays with 4PL model fits!)
• The table of performance characteristics vs validation tests has been updated:
• A new Annex 1 was added.
• Linearity has been replaced by “Working Range” and consists of “Suitability of calibration model” and “Lower Range Limit verification” (QL/DL) Depending on the sample preparation and the analytical procedure selected, the reportable range will lead to a specific working range

At the upcoming BEBPA Hybrid European Bioassay Conference, we have recruited several speakers to discuss what some of these changes imply for potency assays. Two such speakers are:

• Total Analytical Error: The Not Any-More Missing Link Between Validation Guidelines Such as ICHQ2(R2), ICHM10, USP 1033, USP 1210, and Many Others
  Eric Rozet, Director Statistics, Pharmalex Belgium
• Biological Assays Linearity: Making the Link with Assay Intended Use to Derive Fit-forPurpose Acceptance Criteria
  Capucine Lepers, Principal Statistician, GSK

ICH Q14 emphasizes that the scientific principles within it can be applied in a phase-appropriate manner during the product’s lifecycle and are not intended to introduce new regulatory requirements. Q14 defines the concept of the Analytical Target Profile (ATP) and discusses the use of risk assessment to help guide the analytical development.

In potency assays, the primary ATP one needs to understand is the proposed mechanism of action (MoA) of the therapeutic drug. The development group needs to link this proposed MoA to the proposed functional bioassay. Once this is done, Q14 discusses how the analytical development team will identify necessary analytical characteristics of the method. This document also discusses the lifecycle of the procedure.

At the upcoming BEBPA Hybrid EUR Bioassay Conference, several case studies of various development projects will be discussed. These talks will show the nitty gritty of what it really takes to select appropriate assays and develop them for use in a regulated QC lab. These talks include:

• Case Study: Optimization of an Early Phase Enzyme-Based Potency Assay to Detect NN1 Activity
  Jon Christensen, Senior Scientist, Novo Nordisk A/S

• Navigating Phase-Appropriate Potency Testing for Cell and Gene Therapy Products
  Alicja Fiedorowicz, Senior Consultant, Dark Horse Consulting

• Using a Design of Experiments (DOE) to Optimize the Operating Conditions of a Serum Bactericidal Assay
  Capucine Lepers, Principal Statistician, GSK