Decide whether to stay with the same manufacturer

Timothy Scott, president of Pharmatek

The decision whether to use different CMOs for early and late stages of clinical development will differ from company to company and project to project, and depend on budgets and internal resources, amongst other things.

Sometimes using a small and low-cost CMO is the right approach for the early stage of development, particularly for preclinical trials, as the huge costs of clinical development make it important to fail fast and cheap. As Timothy Scott, president of the U.S.-based pharmaceutical chemistry development organization, Pharmatek Laboratories, said to FierceBiotech: "In Phase I and II, the costs of CMC are around $2 million for a small molecule, give or take."

However, a small CMO is unlikely to be able to follow through into later-stage clinical trials, and so the drug developer needs to be prepared from the beginning to change source. It is important to bear in mind that changing CMOs partway through the process can have certain cost implications, and the handover needs to be as seamless as possible to avoid delaying development.

Keeping to the same CMO does maintain consistency between phases, between trials, and even simply between batches of drugs. Variations in clinical trial outcomes are to be expected due to biological variability in the humans taking part in the trials, and the variability of the drugs, which could be due to a range of parameters, including variations in process conditions during drug substance and drug product manufacture or indeed variations in minor impurities, which can have unexpected effects. Because of this, it's important to have flawless process control and complete consistency.

One situation where it can be important to have a CMO locked in place is for later stage development of biologics, because any changes in manufacturing processes need to be made as early as possible in the drug-development process and be flagged up to the regulatory authorities and documented in the submission for approval. Altering the formulation of biologics can also have serious clinical consequences. For example, a change in the formulation of Eprex (recombinant erythropoietin) in 1998 led to the formation of neutralizing antibodies against both the native and recombinant erythropoietin, causing a number of cases of pure red cell aplasia, a form of anemia.

Decide whether to stay with the same manufacturer

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