Pharmaceutical processes, process analytical

Hussain, A. S. (2001), Emerging science issues in pharmaceutical manufacturing Process analytical technologies, paper presented at the Science Board Presentations to FDA, Rockville, MD. 

U.S. Food and Drug Administration, Center for Drug Evaluation and Research, Office of Pharmaceutical Science, Process Analytical Technology (PAT) Initiative, assessed on 12/20/2007, available www.fda.gov/cder/OPS/PAT.htm. 

Several key issues have to be addressed in the downstream processing of biopharmaceuticals regardless of the expression system. The removal of host cell proteins and nucleic acids, as well as other product- or process-related or adventitious contaminants, is laid down in the regulations and will not differ between the individual expression hosts. The identity, activity and stability of the end product has to be demonstrated regardless of the production system. The need for pharmaceutical quality assurance, validation of processes, analytical methods and cleaning procedures are essentially the same. 

This wider definition can be summarized as the analysis of the process and had been developing in the pharmaceutical industry since around 2004-2006 to encourage better use of the information content of classical process analytical methods for the improvement of process development and connol. Particularly in the pharmaceutical industry, the acronym PAT for Process Analytical Technology was often being used to describe this newer definition of process analytics. 

Implementation of process analytics in the pharmaceutical indusUy for continuous improvement purposes has received increased attention in recent years. Process analytics or PAT (see previous definition) has been identified as a key factor in continuous improvement initiatives and is seen as a central element of emerging regulatory strategies to enable these efforts as part of QbD. 

The best practices for the successful implementation of process analytics applications are common to all industries. There are, however, differences in the business model (driver), technical and particularly regulatory areas that are unique to the pharmaceutical industry. The following section seeks to briefly outline these distinctions. 

For the two pronounced phases of drug manufacturing, the technical differences for the use of process analytics between the chemical and pharmaceutical industries are more pronounced in the manufacturing of the formulated drug product than in the chemical synthesis and purification of the API. 

Many technical solutions developed for process analytics in the chemical industry consequently also apply in the pharmaceutical industry. Analyzer systems and implementation principles are essentially the same in both industries (see Chapter 15). 

A short summary of conceptual technical differences with respect to process analytics between the chemical and pharmaceutical industry is listed in Table 2.2. 

Table 2.2 Comparison between chemical and pharmaceutical industry processes with respect to process analytics...

Regulatory aspects of process analytics in the pharmaceutical industry - the concept of quaUty by design... 

Regulatory guidance on process analytics The specifics of regulatory guidance in the pharmaceutical industry are defined in a number of publications, such as ... 

The goal of this section was to outline current differences between the implementation of process analytics in the chemical and pharmaceutical industry, specifically in the areas of business model, technology and regulations. The reader of this chapter should be aware that this status quo is changing rapidly in the pharmaceutical industry due to a changing business cUmate, combined with a more technology-aware regulatory environment in the major pharmaceutical markets. The authors of this chapter would expect that future editions of this book would see major revisions to this comparison of the industries. 

R. Schadt, Process analytical technology - changing the validation paradigm. Pharmaceutical Rev. 7(1) 58-61, January/February (2004). 

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