R. CHRISTIAN MORETON
FinnBrit Consulting, 29 Shawmut Road, Waltham, MA 02452, USA

Abstract

In order to develop the enhanced understanding necessary to demonstrate an acceptable Design Space and Control Strategy required for Quality by Design (QbD) marketing applications, it will be necessary to incorporate the variability in potentially critical excipient parameters into the Design of Experiments (DoE). Methods are described that allow samples to be engineered such that potentially critical excipient parameters can be included in the DoE. However, it must be acknowledged that not all such excipient parameters will be amenable to sample engineering. The excipient manufacturer may be able to provide non-GMP samples which help define the necessary limits for the formulation. The nature of QbD as it relates to excipients is such that communication under a confidentiality agreement between excipient users and excipient makers will be necessary. The necessity for good communication between the excipient user and manufacturer is also emphasized.

INTRODUCTION
According to ICH Q8 (1) Quality by Design (QbD) is “A systematic approach to development that begins with predefined objectives and emphasizes product and process understanding and process control, based on sound science and quality risk management.” In short, QbD requires enhanced understanding of how critical materials attributes (CMAs) and critical process parameters (CPPs) impact critical quality attributes (CQAs) of the pharmaceutical finished product. In exchange for demonstrating this enhanced understanding, the pharmaceutical manufacturer may obtain some regulatory relief post-launch. QbD has changed the excipient and pharmaceutical formulation design and development fields irrevocably.

Excipients are essential components of almost all pharmaceutical products. Without excipients there would be far fewer drug products because many drugs could not be administered to the patient.  Excipients bring properties to the formulation that allow the drug product to be manufactured.

Excipients are a very diverse set of materials. They can be of natural (of plant, animal or mineral), semi-synthetic or synthetic origin. The ...