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Susan J. Schniepp is a fellow at Regulatory Compliance Associates, Inc. and a member of Pharmaceutical Technology's Editorial Advisory Board.
Before embarking on an outsourcing relationship, it's important to be aware of FDA's expectations.
As the pharmaceutical landscape and its related supply chains become more global and complex, industry is in need of more quality agreements. There are several important issues that must be addressed before a company can transfer its product manufacturing to a contract manufacturing organization (CMO). In addition to the facility qualification process, there needs to be a document defining the ongoing relationship and responsibilities of the parties involved. A Technical Agreement, or Quality Agreement, that delineates each party's responsibilities is crucial for assuring that the processes will be controlled according to a mutual understanding. Although constructing a good quality agreement for cooperative manufacturing may seem somewhat predictable and repetitive, each agreement should be approached with a fresh outlook and take into account the strengths and weaknesses of each party.
Susan J. Schniepp
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.
For the latter agreement, FDA's guidance spells out the responsibilities of the license holder and the contract manufacturer. Each party shares responsibility for ensuring the product's safety, purity, and potency, but the ultimate responsibility lies with the license holder. The license holder's responsibilities also include ensuring that the product complies with the biologic license application, current regulations, and product and established standards. In addition, the license holder is responsible for reporting proposed changes to the product or facilities being undertaken by the CMO.
Table I: Responsibilities in contract-manufacturing agreements.
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.