The Role of Enhanced Analytical Procedure Development in Facilitating Post-Approval Changes Via Established Conditions.

Enabling greater flexibility for lifecycle management of analytical procedures is one of the primary features of the International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use (ICH) Q12 Lifecycle Management guideline. Rather than rely on a comparatively slower and burdensome post-approval change supplement process, ICH Q12 created a new pathway to facilitate changes to chemistry, manufacturing, and controls. The new framework utilized key concepts such as established conditions (ECs), post-approval change management protocols, and the product lifecycle management document to allow modifications to analytical procedures based upon pre-approved conditions. Shortly after the publication of ICH Q12, the ICH Q14 Analytical Procedure Development guideline provided further guidance on how knowledge gained during analytical procedure development could be incorporated with the ICH Q12 framework to support scientifically sound and risk-based post-approval changes. However, to date, the full potential of ICH Q12 and Q14 remains unrealized, likely due to uncertainty over how analytical procedure development data can be effectively utilized to gain regulatory flexibility for post-approval changes. In this case study, an example of determining, proposing, and justifying analytical procedure ECs, reporting categories, and identification of elements not considered ECs is presented. In addition, how such information could be presented in a regulatory submission is described. Importantly, this case study serves as an example of the application of ICH Q12 and Q14 principles for analytical procedures, but it is not intended to serve as official guidance nor to define the full scope of information required in a regulatory submission.