FDA's Recommendations to Industry Regarding Outsourcing

How to ensure compliance in the outsourcing environment
Apr 02, 2009


Many drug manufacturers may not have the capability to perform all manufacturing operations at their own establishments for economic reasons. Others opt for subcontracting their operations. Outsourcing introduces considerable complexity into ensuring compliance with good manufacturing practices. This article offers FDA guidance for how to ensure compliance in the outsourcing environment.

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Historically, the manufacture of biological products in the United States involved a limited number of firms that were responsible for all the steps in the process including drug development, testing, labeling, packaging, and distribution to the markets. Since then, an increase in the demand for new products, along with market pressure for innovation, has fostered the growth of specialized firms and subsequent outsourcing.

FDA Defines Outsourcing

According to CDER's guidance for industry, Quality Systems Approach to Pharmaceutical CGMP Regulations, outsourcing involves hiring a second party under a contract to perform the operational processes that are part of a manufacturer's inherent responsibilities.1 For biological products, outsourcing refers to the delegation of manufacturing responsibilities to different types of cooperative arrangements—from the license applicant to a contractor. These arrangements share a common economic goal—bringing products to market more quickly at reduced costs. The FDA's guidance to industry, Cooperative Manufacturing Arrangements for Licensed Biologics, describes different types of manufacturing arrangements for outsourcing.2 Cooperative arrangements recognized by the FDA include: a) a license holder obtaining a short supply product from other than the licensed facilities (see 21 CFR 601.22 for more details); b) two or more licensed firms sharing manufacturing through each firm's individual responsibility for specific aspects of the manufacture of a product with neither being licensed for all aspects of the manufacture; and c) firms performing all or some of the product manufacture as a service to the license holder. Regardless of the type of cooperative manufacturing arrangement, all firms involved in the outsourcing of a manufacturing process must be in compliance with the FDA regulations.

According to the FDA's regulations, the manufacturer is legally responsible for the manufacture of a biological product. Both license holders and contractors fall under this definition because they take part in the manufacture of the biological product. License holders and contractors have responsibilities under the law (see the PHS Act, 21 CFR Parts 210, 211, 600 through 680, and 820 for more details).

The license holder ensures compliance with product and establishment standards through the implementation of current good manufacturing practices (cGMPs). The contractor maintains effective and timely communication with the license holder. Contractors must inform license holders of all deviations in manufacturing methods, adverse events, tests and investigations possibly affecting the product, proposed changes in manufacturing, and any changes in the facilities.

Without exception, all outsourcing participants must comply with FDA regulations. Failure to comply with cGMPs or to fulfill license requirements may justify compliance action. Details for complying with cGMPS can be found in the Food, Drug, and Cosmetic Act (21 USC 301) and the CFR.

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