On May 28, the FDA issued the draft guidance, “Contract Manufacturing Arrangements for Drugs: Quality Agreements.” According to an FDA statement, the guidance “describe[s] how parties involved in the contract manufacturing of drugs can utilize Quality Agreements to delineate their responsibilities and assure drug quality, safety, and efficacy.” The guidance stresses that a Quality Agreement is not a substitute for compliance with CGMP requirements by either party and that the owner of the drug is responsible for the actions of its CMO, in terms of assuring the drug’s quality.

You can download the draft guidance at 1.usa.gov/174eyE8.  Comments are due to FDA by July 29, 2013. For information on submitting a comment, visit 1.usa.gov/12gOhS6.

Prepared by the Office of Manufacturing and Product Quality in the Center for Drug Evaluation and Research (CDER) in cooperation with the Center for Biologics Evaluation and Research (CBER), the Center for Veterinary Medicine (CVM), and the Office of Regulatory Affairs (ORA), the guidance covers an array of products, including human and veterinary drugs, some combination products, drug products, APIs and intermediates and the drug constituents of combination drug/device products. It explicitly does not cover Type A medicated articles and medicated feed, medical devices, dietary supplements, or human tissues intended for transplantation regulated under section 361 of the Public Health Service Act. Some of the CMO operations covered include formulation, fill and finish, chemical synthesis, cell culture and fermentation (including biological products), analytical testing and other laboratory services, and packaging and labeling.

In the guidance, the agency recommends that sponsors and CMOs establish written Quality Agreements in order to best comply with cGMP regulations, include 21 CFR 211.22(d). It also notes that Quality Agreements are not commercial or business contracts and should be separate from Master Service Agreements, Supply Agreements, and the like. A Quality Agreement should cover these basic areas: Purpose/Scope, Terms, Dispute Resolution, Responsibilities (including communication mechanisms & contacts), and Change control and revisions. Areas of responsibility include: Quality Unit responsibilities, facilities and equipment, materials management, product-specific requirements and responsibilities, laboratory controls, and documentation.

The final section offers hypothetical situations that illustrate common problems in CMO arrangements, along with the FDA’s thoughts on possible resolutions, including actions that may be taken against the owner and the contracted facility.