The Choice of Suitable Online Analytical Techniques and Data Processing for Monitoring of Bioprocesses - Measurement, Monitoring, Modelling, and Control of Bioprocesses - page 250

Contents

1 Introduction........................................................................................................................ 250

2 Techniques for Bioprocessing Monitoring ....................................................................... 252

2.1 Heat-Flow Biocalorimetry ........................................................................................ 252

2.2 Dielectric Spectroscopy ............................................................................................ 258

2.3 Vibrational Spectroscopy.......................................................................................... 265

3 Conclusions........................................................................................................................ 273

References................................................................................................................................ 273

1 Introduction

The last decade has introduced a significant number of changes to the pharma-
ceutical and biopharmaceutical industries, not least in the areas of quality assur-
ance and regulatory compliance. This new focus has largely been driven by the
Food and Drug Administration (FDA). In 2002 the FDA announced a new ini-
tiative, ''Pharmaceutical cGMPs for the 21st century'', the purpose of which was to
modernise the regulation of pharmaceutical quality. The initiative supports and
promotes the use of risk-based and science-based approaches for regulatory
decision making, throughout the entire lifecycle of a product [ 1 ]. After 2 years in
development, the final report outlines the envisioned direction in which the
pharmaceutical and biopharmaceutical industries should be moving, but also
provides guidance on how to make the proposed changes and embrace the new
concepts put forward.
Central to the implementation of this new system is the use of science and
engineering knowledge to establish boundaries and evaluate processes. Previously,
a manufacturing process was developed and quality control and assurance tests
were then applied to ensure compliance. This new initiative aims to use knowledge
to mitigate risk, by reducing process and product variability and applying con-
tinuous process improvement. Industry guidelines published by the FDA in May
2006, ''Q8 Pharmaceutical Development'', state, ''quality cannot be tested into the
products, it should be built in by design'' [ 2 ]. Essentially this means that the
rigorous testing of the past cannot improve product quality or enhance the process
but rather quality should be pivotal throughout the lifecycle of a process and a key
factor from the initial stages of development and process design. This introduces
the concept of ''quality by design'' (QbD), whereby a ''design space'' is estab-
lished, within which the product quality profile is defined, the critical quality
attributes (CQAs) and critical process parameters (CPPs) are identified and the
manufacturing process is controlled. Process changes that occur within the design
space are acceptable, as the design space would have been subject to regulatory
assessment and approval at the time the manufacturing process was filed. However