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actively monitored. An effective system is needed to point out issues which arise and to ensure intimate contact with the details of the product development process. The opportunity to intervene in the debate must always be there and must be actively sought if issues arise that affect manufacturing in the future. For example, the sourcing of a key and yet scarce raw material is crucial even at a very early stage of development and requires purchasing expertise from the Manufacturing function. |
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The involvement of the Manufacturing group begins in earnest in the early stages of drug development (i.e., around phase I/II), especially if the program is large and a very aggressive time scale is being pursued. The quantities of material required may mean that a plant scale campaign is needed to satisfy the demand even at this very early stage. There is also need for early involvement to look at a number of primary process issues, for example, |
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the least cost design of the process and the potential routes that can be used to improve robustness and reproducibility; |
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environmental and waste management issues which affect the final process, especially where these have quite a profound effect on company costs. Large waste management plants represent a considerable capital investment, and eliminating the need can often only be done early in the development process. For example, elimination of certain solvent or catalyst residues is achieved through alternative routes. |
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plant and machinery needs with very long lead times. Lead times up to two years are not unknown, especially in the biotech field, where approval of the configuration by regulatory authorities takes some time to achieve. |
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At this stage, involvement of the primary manufacturing team at a technical level is crucial, with lesser involvement for the commercial functions, i.e., Planning/Project Management. Even at this very early stage, however, the Manufacturing staff involved in the project must bear in mind the issues related to the supply of the product on a large scale and avoid compromising later decisions. Another key issue is one of timing relative to the eventual regulatory submission. Some process issues are critical even at the early stage of development. As Manufacturing becomes involved in the primary process issues, the route of manufacture has an intimate relationship with the eventual dossier. Clearly, if manufacture of material for chronic toxicology and carcinogenicity studies takes place by a certain route, this cannot be changed later in the program without further work and potential time |
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