R. CHRISTIAN MORETON
FinnBrit Consulting, Waltham, MA, USA

Abstract

There continues to be confusion around the incorporation of excipients and excipient variability into Quality by Design (QbD) development projects. In particular, there is considerable misunderstanding as to what excipient suppliers can or cannot do in providing samples covering excipient variability and its incorporation into a Design of Experiments (DoE). This paper will discuss excipients and their idiosyncrasies as they relate to the incorporation of excipients into QbD DoEs. It will also discuss ways in which provision of samples at the extremes of specification may be achieved. In addition, the impact of excipients during the product life cycle will be discussed.

INTRODUCTION
Quality by Design requires that the applicant for a marketing authorization demonstrate enhanced understanding of the materials (identify Critical Material Attributes (CMAs) of the bulk active drug (API) and excipients) and processes (identify Critical Process Parameters (CPPs)) used in the manufacture of medicinal products and how they impact the finished product characteristics (Critical Quality Attributes (CQAs)). (1) This enhanced understanding is also a prerequisite for the development of robust medicinal products. A definition of a robust medicinal product has been proposed (2), and is included here for convenience:

‘A robust formulation of a medicinal product is able to accommodate the typical variability seen in: the API, excipients and processes, without compromising the manufacture, stability, performance or any other attribute of the product critical to the patient’s care or well-being.’

In addition, we must recognise that there is inherent variability in our materials and processes. This typical variability is referred to as common cause variation, and this the variability we nee ...