JACQUES WISS
Novartis Pharma AG,
Novartis Campus, CH-4002 Basel, Switzerland

Abstract

This review presents process analytical technology (PAT) methods which are routinely implemented in the pharmaceutical industry. The models for the development and manufacturing procedures are changing from “frozen” processes to more dynamic processes which require online control of critical parameters. Different techniques are described for typical steps in the production of API’s and drug product. These methods are mainly based on spectroscopy and other optical sensors, in combination with chemometric multivariate data evaluation tools. The potential benefits are presented which predominantly lead to quality and safety improvements, costs reductions as well as cycle time reductions.

INTRODUCTION

In 2004 the FDA published its process analytical technology (PAT) guidance (1) and the Good Manufacturing Practice (cGMP) for the 21st Century (2) which requests the design of effective and efficient manufacturing processes to assure product quality and performance. Subsequently in 2005, the European Medicines Agency (EMEA) published its Road Map to 2010 ‘Preparing the Ground for the Future’ (3).
These documents pave the way for a new paradigm allowing significant changes in the development and manufacturing of pharmaceuticals. Most of the pharmaceutical processes are “frozen” usually at the time of conducting phase-2 clinical trials due to the tight regulatory requirements and the long development time for a new drug. Nevertheless, the quality variations of the raw materials (e.g. crystal structure, residual solvent content) and some variability of the process parameters due to the inherent tolerance of the equipment lead to some variability of the product quality. The implementation of PAT facilitates a dynamic manufacturing process that compensates for variability both in raw materials and equipment and thus delivers prod ...