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Do Not Neglect Your Third-Party Drug Substance Manufacturer

Another example of the importance CMC was reported in January. Warner Chilcott plc received a complete response letter from the FDA. The “low dose” oral contraceptive NDA was the file in question. The FDA inspection of the third-party drug substance manufacturing facility and control testing laboratory used to support the application reported outstanding deficiencies which require satisfactory resolution before approval can be allowed.

Everyone down the supply chain is affected when a new drug product launch is held up. These problems can often be avoided with a proactive approach to working with third-party suppliers. The owner of the drug product in question must be present periodically and to inspect the sites providing critical components for their product. Prepare a contract with the third-party that requires communication and draft a quality agreement that meets your internal standards. Confirm that it is being followed.

Adventrx Pharmaceuticals received a refuse to file letter, March 1, 2010. The reason stated was that the data included in the initial submission from the intended commercial manufacturer was insufficient to support a commercially viable expiration dating period. Adventrx believed that they had supported the submission with sufficient stability data: “Site-specific stability data from lots manufactured at the intended commercial manufacturing site also were submitted in the NDA.” Apparently there was not sufficient data on the product manufactured at the intended commercial site. Commercial site data is pivotal, R&D data is supportive.

Neglecting these third-party sites can result in lost revenue every day the new drug product is not on the market.