ANDREI A. ZLOTA
The ZLOTA Company, LLC, 15 Fairbanks Road Sharon, MA 02067-2858, USA

Abstract

Mid-size and small pharmaceutical companies face several challenges in implementing Quality by Design (QbD). In addition to the obvious challenge of limited resources, these companies, not unlike their larger counterparts, face cultural resistance in the adoption of new research and development methods. In this paper we review some of the QbD implementation challenges described recently in an FDA/McKinsey report on the topic. We present herein some of our own observations based on work with a relatively large number of small and mid-size pharmaceutical companies. Ideally there would be only one QbD roadmap, however every company typically prefers to develop a roadmap that best suits their organization. It is important to keep in mind that like many other human endeavours, QbD is best learned by doing, preferably by taking some small steps first.

INTRODUCTION
In 2002 the Food and Drug Administration (FDA) announced a new initiative: “Pharmaceutical Current Good Manufacturing Practices (cGMP’s) for the 21st century” (1). During the past nine years, the International Conference on Harmonization of Technical Requirements for Registration of Pharmaceuticals for Human Use (ICH) has issued several quality guidelines in support of the design of the 21st century cGMP’s (2). These guidelines are not prescriptive, and each organization must apply them as appropriate to their specific projects. As expected, the large pharmaceutical companies started working on QbD implementation soon after the FDA initiative was published. Due to the inevitable resource limitations, medium and small pharmaceutical companies continue to exhibit a slower start of QbD implementation. A 2009 joint FDA/McKinsey report on the status of QbD implementation identifies ten common challenges in the adoption of QbD; six refer to the FDA and four to the industry (3).
The four challenges in QbD implementation that occur within companies are: internal misalignment, lack of technology t ...