Continuous Processing in the Pharmaceutical Industry

For over two decades, the value of continuous processing in the pharmaceutical industry has been recognized. The potential of automation, reduction of capital investment, and the reduction in labor costs has made hot-melt extrusion worthy of consideration. ... 

Plumb, K. (2005). Continuous processing in the pharmaceutical industry. Chemical Engineering Research and Design, 83, 730-738. 

Aseptic processing in the pharmaceutical industry is almost entirely dependent upon the proficiency of the personnel assigned to this most critical of all activities. The operators must be able to consistently aseptically transfer sterile equipment and materials in a manner that avoids contamination of those materials [1]. This is no mean feat given the contamination continuously released by personnel and the prevailing need for personnel for execution of the process activities. 

Another major drawback of continuous production is related to the quality assurance of the manufactured goods, more specifically to the documentation of the production run documentation of a continuous process emphasizes process control, whereas a batch process emphasizes recording. Therefore the recent advances of process analytical techniques (PATs) are of great importance for the further implementation of continuous production in the pharmaceutical industry. 

The product development process in the pharmaceutical industry is not unlike that of other industries, in which exploratory materials are researched and developed into products, and where problems arise the analytical laboratory is called upon to provide solutions. The characterization of the physical properties of pharmaceutical solids is one of the disciplines utilized early in the drug development process. The characterization of these properties is vital to determining whether the compound under investigation is a candidate for continued development as a drug product. To facilitate the characterization of pharmaceutical solids in laboratories, a conceptual approach for this characterization has been developed (66) that uses decision trees to guide the analyst in the characterization of drug substances. 

Continuing evolution of the drug discovery process in the pharmaceutical industry 01PAC67. 

However, it cannot be assumed that all processes in the pharmaceutical industry worldwide have been properly validated at the development stage. Consequently, validation is discussed here in a broader context as an activity which is initiated in development and is continued until the stage of full-scale production is reached, in fact it is in the course of development that critical processes, steps or unit operations are identified. 1... 

A. Franke, M. Leitgeb, G. Jas, From Vision to Realization - Continuous Processing in the Pharmaceutical and Fine Chemicals Industry, Crystal Faraday Symposium, London, 2004. 

In the pharmaceutical industry, and to some extent the fine chemicals industry, an important advantage of a batch reactor is traceability. The product from a particular batch will have a uniform consistency, and can be uniquely labelled and readily traced. In contrast, the product from a continuous process may change gradually over time, and it is therefore more difficult to trace a particular impurity or fault in the material. Batch reactors are, however, rarely the most efficient in terms of throughput and energy use when the reaction kinetics are fast. Batch systems are also much more labour intensive than continuous processes. 

Over time, scientists have built up a large body of knowledge about many different catalysts and enzymes. This knowledge has been put to good use in industry. Difficult and expensive industrial processes have been made faster, cheaper, and easier through the use of catalysts and enzymes. For example, enzymes are used in the pharmaceutical industry, in paper-making and recycling processes, and in the petroleum industry. Many more industrial uses of catalysts and enzymes are possible, and research into catalysts continues. 

Impurities in drug substances and drug products continue to be a source of great concern, discussion, debate, and research. " These concerns and debates typically center on the potential safety risks associated with impurities due to contamination and the setting of acceptance criteria. However, the bulk of the work being performed in the pharmaceutical industry, with respect to impurities, is focused on the isolation, identification, qualification and quantification of impurities that are found as a result of the manufacturing process or through chemical decomposition. On the... 

Once approved by the regulators, commercial manufacturing processes are launched and the principles of continuous improvement are applied. These principles have been widely used in the chemical industry due to their large potential for economic benefits and now also have been adopted in the pharmaceutical industry, partially enabled by the QbD initiative. 

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