Purge Your System

Do you use Purge calculations as a fundamental part of your process for effective management of Mutagenic Impurities?

Andy Teasdale, author of ‘ICH Quality Guidelines – An Implementation Guide’ has recently published some case studies with co-workers [https://pubs.acs.org/doi/10.1021/acs.oprd.4c00207] which he will also include in his training course later this year. Andy says…

Recently the journey associated with Purge calculations took another step forward through the publication of a series of cases studies that seek to provide clarity on when additional data or information can be useful to give greater support to an ICH M7 Option 4 control.  Since I worked on original concept we have seen the use of such calculations, often aligned with Mirabilis, become an integral part of MI risk assessments.  Long before the concept of digital twins and in silico aided process design became the desired norm, purge calculations have provided an clear insight into MI related risk and its control.  Such concepts are integrated into the ICH M7 guideline, “Assessment and Control of DNA Reactive (Mutagenic) Impurities in Pharmaceuticals to Limit Potential Carcinogenic Risk”. This guideline highlights four control options, which can be used to give assurance of control of PMIs to below a level of concern for the intended patient. These controls vary from testing to confirm levels within the active pharmaceutical ingredient or product (ICH M7 Option 1 Control) to a control strategy that relies on process controls and scientific principles in lieu of analytical testing, which can include considerations of fate and purge (measured or predicted) (Option 4).

These case studies range from examples that have been approved by health authorities for clinical applications and marketing authorizations to those that have not been submitted to regulators at this time. It focuses on the use of sound data and scientific rationales to support the ICH M7 Option 4 control strategies where the purge ratio may not initially show such an option. The study provides an industry perspective of Option 4, approaches with an emphasis on the types of supportive datasets and scientific principles that can be used while remaining aligned with the intention of the ICH M7 guideline, and elaborates on the differences between the various control options.

As part of my impurities training course I will talk in detail as to how the use of purge calculations form a fundamental part of the systematic process for effective management of MIs now adding this paper to the training.