US FDA finalises contract manufacturing quality agreement guidance

A written quality agreement between a sponsor and a contract manufacturer can facilitate compliance with cGMP, the US FDA says in its finalised guidance.

The final guidelines – ‘Contract Manufacturing Arrangements for Drugs: Quality Agreements’ – were published this week by the US Food and Drug Administration (FDA) setting out the roles and responsibilities for the owner of a drug and a contract manufacturing organizations (CMO) in terms of cGMP (current good manufacturing practices) regulations.

“When an owner uses a contract facility, the owner’s quality unit is legally responsible for approving or rejecting drug products manufactured by the contract facility, including for final release,” the guidance states. “The regulations require that the quality unit’s responsibilities and procedures be in writing and that they be followed.”

As such, the FDA recommends owners using a quality systems model – an agreement between parties involved in the contract manufacturing of drugs that defines and establishes each party’s manufacturing activities in terms of how each will comply with CGMP – as a tool to delineate manufacturing activities, aiding compliance.

Quality agreements are not an FDA requirement but the Agency has previously sent warning letters to sponsors for failing to set one up with their CMO.

“A comprehensive quality systems model anticipates that many owners will use contract facilities and calls for quality agreements between owners and contract facilities. Quality agreements should clearly describe the materials or services to be provided, quality specifications, and communication mechanisms between the owner and contract facility.”

This would allow the owners and contract facilities to “draw on quality management principles to carry out the complicated process of contract drug manufacturing by defining, establishing, and documenting their activities in drug manufacturing operations,” the Agency adds.

Industry comments

The final guidance has taken on board some of the comments from industry criticising the scope and applicability of the quality agreements in a draft published in May 2013.

“We have clarified that the guidance is limited to commercial manufacturing activities,” the Agency said in the Federal Register. “Although the principles articulated may be useful in approaching quality agreements for other kinds of activities, such as clinical research, development, or distribution, these are outside the scope of this particular document.”

Drugmakers also criticised the terminology used in the draft.

“Although some comments recommended that this guidance adopt the terms ‘contract giver’ and ‘contract acceptor,’ these terms do not align with our goal of showing how the parties to a contract manufacturing arrangement can work together to define, establish, and document agreements that delineate manufacturing activities and ensure compliance with CGMP.”