13/14 December 2023
The U.S. Food and Drug Administration FDA has published the draft Guidance for Industry "Contract Manufacturing Arrangements for Drugs: Quality Agreements".
In the EU GMP Guide Chapter 7 on Outsourced Activities, expectations regarding quality contracts are clearly defined. In the US, not much detail was provided so far. CFR regulations do not explicitly require contract partners to document their respective responsibilities in contract manufacturing arrangements, but the regulations do require that Quality Unit responsibilities and procedures are in writing (21 CFR 211.22(d)). With the new Guidance, the FDA aims to describe the agency's current thinking on defining, establishing, and documenting the responsibilities in contract manufacturing of drugs subject to Current Good Manufacturing Practice (cGMP).
Quality Agreements covered in this document are not commercial or business agreements and FDA therefore recommends that Quality Agreements are separate documents.
The new draft guidance describes the obligations of the contracting parties, the delineation of responsibilities and how drug quality, safety, and efficacy can be assured in contract manufacturing. It applies to the commercial manufacturing of:
The term "manufacturing" in the sense of this document includes processing, packing, holding, labelling operations, testing, and operations of the Quality Unit.
No matter, which activities are outsourced, the Quality Unit of the contract giver ("Owner") will stay ultimately responsible for approving and rejecting drug product manufactured by the contract manufacturer (21 CFR 210.3(12)). This is different to Europe, where the release (certification by a Qualified Person) can also be outsourced.
The basic sections which might be expected by FDA are:
At the end of the document, hypothetical scenarios illustrate some common problems in contracted manufacturing arrangements. The scenarios also demonstrate FDA's thinking regarding possible resolution of the problems. The examples provided are not intended to be exclusive, but, instead, to provide industry and other stakeholders with some frequently-encountered fact patterns and our analysis of those facts.
This guidance document is being distributed for comment purposes only. Comments and suggestions regarding this draft document should be submitted within 60 days of publication in the Federal Register. Guidance documents describe the Agency's current thinking on a topic and should be viewed only as recommendations, unless specific regulatory or statutory requirements are cited.