Gallenical Forms

A good rule of thumb is that pivotal clinical trials for registration purposes ought to be conducted with the same formulation and manufacturing process that is proposed to be taken to market. While the nuances of pharmaceutical constructs are described in Chapter 5, it is important to understand the sometimes grave consequences when this rule of thumb is not observed.

Most regulatory authorities will want reassurance that the pharmacokinetic properties of the marketed product closely resemble those in which the pivotal studies are carried out. This is not unreasonable: if the pharmacokinetic (PK) properties differ, then so may dose size and frequency. Occasionally, a Phase III study will be 'bridged' to the marketed formulation by the demonstration, for example, that two different tablets have the same PK profile. However, the risk is that different formulations will not turn out to possess the same PK profile: either new pivotal studies will have to be conducted with the new formulation, or registration will be delayed until the new formulation is adapted so that it does match the Phase III test material. For inhaled drugs, this is especially difficult. Time and money is often lost in both cases. It is a risky gamble to leave development of the final formulation until the end of a clinical development plan.

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