Manufacturing, pharmaceutical process design

Process validation is the procedure that allows one to establish the critical operating parameters of a manufacturing process. Hence, the constraints imposed by the FDA as part of process control and validation of an SMB process. The total industrial SMB system, as described, is a continuous closed-loop chromatographic process, from the chromatographic to recycling unit and, with the use of numerical simulation software allows the pharmaceutical manufacturer rapidly to design and develop worst-case studies. 

The first chapter in this section provides a unique account of the ecology, i.e. distribution, survival and life-style, of microorganisms in the factory environment, and should enable process designers, controllers and quality control personnel to comprehend, trace and eradicate the sources of failure due to extraneous microbial contaminants in the finished product. Much of the information given here is applicable to hospital manufacture also, and this is extended in a contribution (Chapter 19) dealing with contamination in hospital pharmaceutical products and in the home. 

Validation of aseptic pharmaceutical processes is specihcally assembled in the second edition as a reference for use by managers, supervisors, and scientists in the pharmaceutical industry. The primary intent of this work is to guide design engineers, manufacturing personnel, research and development scientists, and quality control professionals in validating those processes needed for nonaseptic and aseptic pharmaceutical production. 

The key objective of this chapter is to describe a generic and systematic pharmaceutical manufacturing/assembly system design method that includes product, process, service systems, and even innovation project management architecture aspects of such systems. 

A Life Cycle Inventory/Assessment (LCI/A) is used to determine the overall amounts of materials used, waste generated, and energy used during the manufacture of solvents, their use in pharmaceutical processes, and their eventual disposal. Many processes today are designed with an emphasis on solvent recovery to help reduce the costs associated with purchasing fresh solvent and waste... 

Pharmaceutical formulation and process development should provide sufficient information and knowledge to understand and support establishment of the design space, specifications, and manufacturing control. The design space of QbD is defined as the multidimensional combination and interaction of input variables (e.g., material attributes) and process parameters that have been demonstrated to provide assurance of quality.6 Because multiple variables in formulation and process can be encountered, it is important to use an effective methodology to define the design space. 

Similarly, when moving from the pilot plant to manufacturing, a process engineer will either choose an existing vessel or specify the design criteria for a new reactor. A necessary condition for operation with a specified reactor temperature profile is that the required jacket temperature is feasible. We have therefore chosen to focus on heat transfer-related issues in scale-up. Clearly there are other scale-up issues, such as mixing sensitive reactions. See Paul [1] for several examples of mixing scale-up in the pharmaceutical industry. 

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