The regulatory and compendial pathways to acceptance for AIM and EDA concepts

Abstract

The acceptance by the regulatory and compendial authorities of AIM and EDA concepts is a critical stage before their widespread adoption by the pharmaceutical industry will likely take place. A prerequisite for such acceptance will be the assemblage of a body of data in which close attention has been placed not only on the methods themselves but also on their applicability across as wide a portion of the spectrum of OIP classes as possible. In the case of AIM-based apparatuses, it will be important to provide experimental data from many inhalers of each type, so that the variability of the method can be assessed in the context of typical variability associated with the corresponding full-resolution method. Robust statistical analysis of either full-resolution APSDs or AIM CI-generated APSD metrics by EDA, in comparison with existing data reduction methods (i.e., stage grouping, fine/total particle mass), will be needed to justify replacing current methods. A vital part of this process will be demonstrating that EDA is capable of at least matching current methods and preferably is shown to have better decision-making capability, in the context of quality control for most OIPs. AIM-based apparatuses may have roles in the development of testing capacity to work with improved material and process understanding, implementation of in-process controls prior to final product, and minimization of capacity spent on end product controls. Given precedents for the pace of change, compendial and regulatory acceptance will likely take several years to be realized. This chapter begins by assessing the current regulatory guidance and compendial requirements with respect to the use of cascade impaction or when APSD data is required. The second part of the chapter discusses strategy and requirements that the pharmaceutical industry involved with OIP assessment is likely to have to provide to demonstrate that AIM and EDA are fit for purpose and thereby gain acceptance by the regulators and become a pharmacopeia-approved method.