ABSTRACT
The pharmaceutical current good manufacturing practices (cGMP) for the 21st Century Initiative was implemented by the Food and Drug Administration (FDA) in 2002 to enhance and modernize the regulation of pharmaceutical manufacturing (FDA GMP Guidance 2002a). Some of the key concepts from this initiative emerged in the form of the guidance PAT-A Framework for Innovative Pharmaceutical Manufacturing and Quality Assurance (FDA PAT Guidance 2004). The scientific, risk-based framework outlined in this guidance, process analytical technology or PAT, is intended to support innovation and efficiency in pharmaceutical
10.1 Introduction .................................................................................................. 179 10.2 PAT Applications in the Pharmaceutical Industry ....................................... 180 10.3 Definition of PAT .......................................................................................... 181
10.3.1 Design ............................................................................................... 182 10.3.2 Analysis ............................................................................................ 185 10.3.3 Control .............................................................................................. 185
10.4 PAT Application in Bioseparation Unit Operations ..................................... 185 10.4.1 Centrifugation ................................................................................... 186 10.4.2 Flocculation ...................................................................................... 186 10.4.3 Extraction .......................................................................................... 187 10.4.4 Precipitation ...................................................................................... 188 10.4.5 Filtration ........................................................................................... 190 10.4.6 Refolding ........................................................................................... 192 10.4.7 Chromatography ............................................................................... 194
10.5 Conclusion .................................................................................................... 195 References .............................................................................................................. 196
development, manufacturing, and quality assurance. The framework is founded on process understanding to facilitate innovation and risk-based regulatory decisions by industry and the agency. The approach is based on science and engineering principles for assessing and mitigating risks related to poor product and process quality. In addition to the PAT guidance, three important guidance documents were published as part of the International Conference on Harmonization (ICH) guidelines: ICH Q8 Pharmaceutical Development, ICH Q9 Quality Risk Management, and ICH Q10 Pharmaceutical Quality System (ICH Q8 Guidance 2009; ICH Q9 Guidance 2005; ICH Q10 Guidance 2008). PAT-related activities also occurred in other regulatory jurisdictions. A European Medicines Agency (EMEA) PAT team was created in November 2003 with the aim to review the implications of PAT and to ensure that the European regulatory framework and the authorities are prepared for and adequately equipped to conduct thorough and effective evaluations of PAT-based submissions. A reflection paper has been published that provides preliminary recommendations on how PAT-related information should be presented in regulatory applications (EMEA Reflection Paper 2006).
