SUMMARY

When embarking on a pharmaceutical development program, an innovator organization will have to make decisions about how key development operations are contracted out. These decisions can be complex because CMOs will have complementary and partially overlapping capabilities, and constraints in terms of scale of manufacture. The initial choice of CMO to provide drug substance and drug product may be sufficient for early-stage clinical trials. Often, for parenteral dosage forms, formulation development, analytical method development, and validation, release, and stability testing are carried out by the drug substance manufacturer, and the fill–finish operations are performed by the CMO. The amount of effort spent trying to optimize the formulation and presentation of the drug product so that it is fit for purpose for early-stage clinical trials must be considered in the broader context of business and resource constraints. This arrangement is common and may work for early-stage development. However, should the pharmaceutical development program progress beyond Phase 1–2 clinical trials, the innovator organization faces a further set of decisions. It is at this stage, when there is confidence in the potential efficacy of the drug, that changes to the formulation and presentation are likely to be made so that they are more suitable for late-phase clinical trials or for a marketed product.

To ensure regulatory compliance, these changes also will require revalidation of analytical methods. The requirements of increased scale of manufacture must considered. The innovator organization must determine whether its CMO network can meet the requirements for later stage clinical trials and beyond, or if the balance of manufacturing or development activities must be shifted.