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delays. The carcinogenicity study start date is the key watershed, the route intended for market must be final by then, with a fixed and well-understood impurity pattern. This leads to a submission for a route that must be supported by primary production and the equipment available, minimizing the need for immediate change after approval. Involvement with Chemical Development in the production of material for six-month animal studies and beyond is obviously a crucial interaction in ensuring the shortest possible overall development time. There is some secondary manufacturing involvement, especially where a novel dosage form is envisaged, such as a new type of solid dosage form or an inhaler. Secondary Manufacturing, therefore, has to be informed about the development and take part in key decisions about its dosage form/pack design, but may not wish to become fully involved at this very early stage where it is highly possible that the molecule will fail. |
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As development progresses into late phase II and phase III, the involvement of Manufacturing inevitably grows and this is the point at which they must be fully represented on the project. The involvement of Primary Manufacturing remains, of course, and with the R & D team, they will have begun finalization of the process which will be used in the final dossier. Around phase III and leading up to the initial submission, a number of important issues must be dealt with, for example, |
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process scale up and tailoring this to the plant available with appropriate validation of the reproducibility; |
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make or buy decisions where technically it may be easier for a specialist contractor to take on a particular part of the process rather than investing in-house; |
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the relationship with the secondary process in terms of specifications for the drug substance, e.g., particle size or moisture content. |
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In addition to the above primary process technical issues, a wide range of commercial issues also arise now which relate to the drug substance, for example, |
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Where should manufacturing be located to optimize costs and simplify logistical considerations while supporting secondary production to an optimal degree? Can nursery production plants be used initially to help stabilize the process prior to transfer into main production sites? |
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What is the likely demand for the eventual product? How will this be serviced and does this raise significant purchasing issues? |
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Is plant investment needed to support the expected peak demand? |
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