Regulations and Drug Master Files

For researchers the relevance of regulations often seems remote, and yet the decisions taken in even the earliest stages of research can take on a great significance if the target product becomes a commercial

Figure 9 Horse liver alcohol dehydrogenase separation. Using the modified Cibacron Blue F3G-A (Figure 7) structure given above, the selectivity is greatly enhanced making it possible to separate the isoenzymes.

reality. It is regrettable that many researchers slavishly follow previously published data on a given separation problem without giving thought to the longer-term implications of their decisions. Sections above describe the adverse economic effects of multistage processing, but an equally important factor is regulatory issues. The most widely used regulations are those defined by the USA's Food and Drug Administration (FDA). Any company wishing to import products relevant to regulations existing in the USA must conform exactly to FDA requirements; drugs in particular are very strictly controlled. Detailed descriptions of any plant and process used in drug manufacture have to be lodged in documented form with the FDA, wherein every aspect of process description is given. This must include raw material definition and suppliers, stability data for every step of the process, formulation methods, packaging, labelling, toxicity data and so on. The documentation has to be revised annually and any changes notified. Furthermore plant and process is open to inspection at all times for full audit of procedure. There is one large anomaly within the regulations. The largest volume of material in contact with a drug during manufacture is water, solvents and salts, all of which are exactly defined in terms of their physicochemical characteristics. The next largest is chromatographic media; ambiguously media do not have to be described in the same detail.

The outstanding stability of the synthetic chromatography media provides an excellent opportunity to develop and register Drug Master Files

Figure 10 Model of the Phe-Arg dipeptidyl substrate bound in the acitve site of porcine pancreatic kallikrein. The illustration shows Asp189 at the bottom of the primary binding pocket as well as the side chains of Tyr99 and Try215, which form the secondary binding pocket, with the phenyl ring of the Phe residue sandwiched between the hydrophobic side chains of these residues.

Figure 10 Model of the Phe-Arg dipeptidyl substrate bound in the acitve site of porcine pancreatic kallikrein. The illustration shows Asp189 at the bottom of the primary binding pocket as well as the side chains of Tyr99 and Try215, which form the secondary binding pocket, with the phenyl ring of the Phe residue sandwiched between the hydrophobic side chains of these residues.

(DMFs) with the FDA. DMFs allows companies to use synthesized ligands for very high purity protein pharmaceuticals with total confidence. New Drug Applications (NDA) and Investigational New Drugs (IND) documents incorporating such stable affinity media can now be submitted to the FDA, safe in the knowledge that all appropriate information is on file. The effective guarantee of minimum quality

Figure 11 Comparison of the structures of (A) the Phe-Arg dipeptide, and (B) the 'biomimetic' ligand designed to bind at the active site of the porcine pancreatic kallikrein.

Figure 11 Comparison of the structures of (A) the Phe-Arg dipeptide, and (B) the 'biomimetic' ligand designed to bind at the active site of the porcine pancreatic kallikrein.

standards and Good Manufacturing Practice (GMP) is an integral part of a DMF. Few researchers selecting a specific medium consider the long-term implications of stability under depyrogenating conditions, the number of cycles that can be achieved (lifetime in use), its availability in bulk, whether it is manufactured under aseptic conditions and the price when supplied in bulk. If the researcher makes a good initial selection, the research data produced can be utilized in development phases with confidence. 'Fast tracking' is facilitated, with minimum aggravation, maximum efficiency and minimum purification costs.

Solar Panel Basics

Solar Panel Basics

Global warming is a huge problem which will significantly affect every country in the world. Many people all over the world are trying to do whatever they can to help combat the effects of global warming. One of the ways that people can fight global warming is to reduce their dependence on non-renewable energy sources like oil and petroleum based products.

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