Process evaluation specification

The National Bureau of Standards has a unique role to play in supporting the field of chemical engineering. It should be the focal point for providing evaluated data and predictive models for data to facilitate the design, the scale-up, and even the selection of chemical processes for specific applications. 

It is beyond the scope of this chapter to discuss and explain how the requirements can be implemented in analytical laboratories. This has been described in a six-article series published in Biopharm [16-21]. We elaborate here on the validation aspect of the rule. Part 11 requires that computer systems used to acquire, evaluate, transmit, and store electronic records should be validated. This is not new, as processes and steps to validate such systems were described earlier in the chapter. FDA s expectations for validation have been described in the Part 11 draft guidance on validation [4]. This guidance makes it very clear that functions as required by Part 11 should be validated in addition to functions that are required to perform an application such as chromatographic instrument control, data acquisition, and evaluation. Specific functions as required by Part 11 are as follows ... 

To assess the impact of drug substance particle size and size distribution on a formulation, prepare two to three batches of drug substance with different mean particle sizes for formulation and process evaluation. This helps establish a specification to control particle size and size distribution of the drug substance. 

Application of the Recommended Evaluative Process to Specific Chemicals... 

The nomenclature for early clinical studies is not fully standardized. In addition to first-in-human evaluations, Phase I trials are appropriate throughout the drug development process as specific issues arise that require clinical pharmacologic investigation. Further, some exploratory hrst-in-human studies are currently being described as "Phase Zero," in which the goals are somewhat different from classic Phase I trials. 

It is evident that attention paid in the laboratory to the factors affecting particle size distribution will save on capital investments made for separation equipment and downstream process equipment. Specific cake resistance (a) can be determined in the laboratory over the life of a batch, to evaluate if time in the vessel and surrounding piping system is degrading the product s particle size to the point it impedes filtration, washing and subsequent drying. 

Once the clinical and safely evaluation studies for a new medicinal product have shown it to be safe, effective and of acceptable quality, the pharmaceutical company will usually want to submit a Marketing Authorisation Application (MAA) or New Drug Application (NDA) to the regulatory authorities. The chemistry, manufacturing and controls (CMC) section will form a major part of the application. For an MAA in Europe, a development pharmaceutics section is required to describe how the product was developed, and to explain the rationale for the selection of the formulation, pack, manufacturing process and specifications. Also required for Europe are expert reports for each of the pharmaceutical, safety and clinical parts of the application. These have to be written by experienced scientists nominated by the pharmaceutical company who have to critically appraise the development programme for the product. The pharmaceutical expert must acknowledge the acceptability of the CMC part of the application. 

Evaluation of competitive products and processes in specific applications. 

There are four specific tasks (1) HDPE treatment and development of alternative tank liner materials for hydrogen gas permeation reduction (2) enhancing epoxy resin toughness to improve the tank carbon liber overwrap performance (3) materials and process evaluation for manufacturing the ISS protective shell and (4) engineering an optimized unitary gas control module. An additional task (5) is the formulation of a roadmap for protot5q)ing and... 

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