Recognizing the challenges and opportunities of the CMO model, the US Food and Drug Administration published in 2008 a guidance document, Cooperative Manufacturing Arrangements for Licensed Biologics, to provide information about the agency's expectations regarding quality agreements for biological products. Both FDA's Center for Biologic Evaluation and Center for Drug Evaluation and Research endorse the guidance, which describes four types of manufacturing arrangements: Short Supply, Divided, Shared, and Contract.
A Short-Supply agreement is a specialized agreement used in situations where a necessary product is facing a potential out-of-stock situation. Divided manufacturing agreements are used when two manufacturers, each registered with FDA, are licensed to manufacture a specific product in its entirety and agree to jointly manufacture the product. Shared manufacturing arrangements are defined as agreements where two or more manufacturers are licensed to perform one or more parts of the synthesis of a product, but none of the companies are licensed to manufacture the entire product from beginning to end. Finally, Contract manufacturing arrangements, the most prevalent today, are, in essence, service agreements, where the license holder contracts with another company to manufacture the product for them.
According to the guidance, CMOs must comply with current regulations. They are subject to FDA inspections and must be registered with the agency. The CMO should be prepared to provide pertinent information to the license holder, including facility floor plans and equipment validation. Both the CMO and the license holder should have robust procedures in place for informing and receiving information on deviations, complaints, adverse events, and the results of tests and investigations affecting the product(s) being manufactured. There are many more responsibilities discussed in the guidance document (see Table I), but the bottom line is that the license holder is responsible for the behavior and conduct of its partnering CMO.
Regardless of which manufacturing arrangement companies use, it's important to understand the contents and recommendations of this FDA guidance and to structure quality agreements accordingly. One key element in this process is communication. The types of and speed with which information is communicated is vital to establishing a good working relationship between the parties implementing a quality agreement. Information-exchange is also pertinent to meeting FDA's expectations.
Susan J. Schniepp is vice-president of quality at Antisoma in Cambridge, MA, Susan.Schniepp@antisoma.com