FDA Issues Draft Guidance on Contract Manufacturing

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The draft guidance describes how quality agreements can be used to delineate the responsibilities of contract manufacturers involved in the cGMP manufacture of APIs and finished drug products.

FDA has issued draft guidance,Contract Manufacturing Arrangements for Drugs: Quality Agreements, which describes the agency’s current thinking on defining, establishing, and documenting the responsibilities of each party (or all parties) involved in contract cGMP manufacturing of drugs.

In particular, the draft guidance describes how parties involved in the contract manufacturing of drugs can use quality agreements to delineate their responsibilities and ensure drug quality, safety, and efficacy. This guidance applies to the commercial manufacturing of APIs (drug substances or their intermediates), finished drug products, combination products, and biological drug products. For the purposes of this guidance, the term “manufacturing” includes processing, packing, holding, labeling operations, testing, and operations of the quality unit.

For purposes of the draft guidance, in discussing the roles and responsibilities of the parties in contractual relationships, the “owner” is defined as the party that introduces (or causes the introduction of) a drug into interstate commerce, whether such drug is covered by a marketing application/license or not. The “contracted facilities” are the outside entities performing manufacturing operations for the product owner. Some of the manufacturing operations performed by such contracted facilities include: formulation, fill–finish, chemical synthesis, cell culture and fermentation (including biological products), analytical testing and other laboratory services, and packaging and labeling. The draft guidance specifies that the owner is responsible for ensuring that drugs introduced for interstate commerce are neither adulterated nor misbranded as a result of the actions of their selected contracted facilities, and all contracted facilities must ensure compliance with applicable cGMP for all manufacturing, testing or other support operations performed to make a drug(s) for the owner.

The draft guidance describes how contract manufacturing operations fit within the larger scheme of pharmaceutical quality systems and presents FDA’s current thinking on the roles and responsibilities of entities involved in contract manufacturing arrangements. FDA says the draft guidance incorporates provisions from ICH guidelines, including ICH Q7 Good Manufacturing Practice Guidance for Active Pharmaceutical Ingredients, ICH Q9 Quality Risk Management, and ICH Q10 Pharmaceutical Quality Systems.


The draft guidance notes that although written quality agreements are not explicitly required under existing cGMP, owners and contracted facilities can draw on quality management principles to carry out the complicated process of contract drug manufacturing by defining, establishing, and documenting the responsibilities of all parties involved in drug manufacturing, testing, or other support operations. Accordingly, FDA recommends that owners and contracted facilities implement written quality agreements as a tool to delineate responsibilities to ensure the quality, safety, and effectiveness of drug products.

Comments and suggestions regarding the draft guidance should be submitted within 60 days of publication in the Federal Register of the notice announcing the availability of the draft guidance.