ØYVIND HOLTE
Norwegian Medicines Agency,
EMA PAT team, EDQM PAT WP
P.O. box 63, Kalbakken, NO-0901 Oslo, Norway

Abstract

Over the last decade, we have seen several initiatives by both Industry and Authorities related to the introduction of novel approaches to pharmaceutical development, manufacturing and process control. New concepts have been established, such as enhanced approach to development, Quality by Design (QbD), Process Analytical Technology (PAT), Design Space (DSp) and Real Time Release testing (RTR testing). Considering that the new concepts were introduced with the best of intentions, the current situation for these approaches in regulatory submissions is not quite as anticipated. Both the industry side and the regulatory side seem to struggle to reap the expected benefit, namely a more efficient and robust manufacturing of quality drug products. Novel approaches to development, manufacture and control of drug products are acceptable, when appropriately justified and explained. Careful communication between Industry and Regulators should improve the situation for QbD/ DSp in regulatory submissions.

BACKGROUND

The manufacture of pharmaceutical preparations is strictly regulated, compared to other types of products and industries. There are good reasons for this, including experienced quality issues leading to illness or death (1). The responsibility for the quality of each batch of drug product lies with the manufacturer. Competent authorities monitor each drug product that is marketed in their region by inspection of involved manufacturers and by approval of the marketing authorisation (MA), including changes to the MA over the product life cycle. Included in the MA is a detailed description of the manufacturing process and the associated process controls. Another central element of the MA is the approved specification of the product, which represents the quality standard of that product. There are alternative strategies available to demonstrate compliance with the specification. The MA holder’s approach is sometimes referred to as his Control strategy. Quality by Design (QbD) and Design space (DSp) represent new approaches to ensure the product quality. In the following, some of the perceived regulatory hurdles to such approaches are highlighted ...