FDA issues draft guidance on contract manufacturing arrangements

Agency seeks comments on roadmap for quality agreement preparation

Lori Lesko
WASHINGTON D.C.—On May 28, the U.S. Food and DrugAdministration (FDA) unveiled its latest draft guidance on contract manufacturingarrangements for drugs. To some extent, the FDA's guidance is a roadmap on howto prepare a quality agreement and signals the FDA's interest in advancingquality manufacturing through the use of written agreements.
 
 
The draft guidance, "Contract Manufacturing Arrangements forDrugs: Quality Agreements," was published May 28 by the FDA to clarify theagency's current thinking on the obligations of each entity involved in thecontract manufacturing of drugs and how such agreements may be used to outline responsibilities.The FDA's guidance applies to the commercial manufacturing of activepharmaceutical ingredients, finished drug products, combination products andbiological drug products, but places responsibility on most everyone involvedin the manufacturing process to maintain the highest quality agreementstandards.
 
 
While the scope of the guidance is limited to drugs enteringthe market and not those intended for research, the FDA uses the termmanufacturing to include "processing, packing, holding, labeling operations,testing and operations of the quality unit." The guidance defines a qualityagreement as: "A comprehensive written agreement that defines and establishesthe obligations and responsibilities of the quality units of each of theparties involved in the contract manufacturing of drugs subject to current GoodManufacturing Practice (cGMP) requirements. In general, the quality agreementshould clarify which of the CGMP activities are to be carried out by each partyper the applicable regulations."
 
 
Although quality agreements are an important tool to ensurea drug's safety and effectiveness, the drug sponsor and the contractor mustcomply with cGMP requirements, regardless of their inclusion (or not) in thequality agreement.
 
A number of major manufacturers for drug companies andpharmaceuticals were asked their opinion of the FDA guidelines, but all beggedoff, asking for more time to study its contents or preferring to wait untilafter the deadline for written comments.
 
FDA regulations do not explicitly require parties involvedin contract manufacturing to document their responsibilities, although theregulations note, "the responsibilities and procedures applicable to thequality unit shall be in writing." A written quality agreement facilitatescompliance with this cGMP requirement.
 
 
The new draft guidelines also include recommendations foragreement format, purpose and terms, as well as provisions for disputeresolution, outlining of responsibilities and obligations, change control and revisions,facilities and equipment, materials management, documentation and finalapproval.
 
 
To drive its point home, the FDA guidance refers to two U.S.Supreme Court decisions to remind the industry of individual and criminalexposure for non-compliance with applicable law. According to court justices'rulings, a contractor cannot agree to manufacture under non-cGMP conditions,and the quality agreement will not serve as an excuse for manufacturing drugsin a non-compliant manner.
 
 
The FDA also states that if a quality agreement's termsbecome inadequate, the contractor should cease operations or bear the costs tomodify operations to maintain regulatory compliance and seek redress from thedrug sponsor. In addition, the drug sponsor cannot delegate final productrelease of finished goods for distribution if the quality agreement's terms arebreached. Similarly, the FDA may hold the drug owner or sponsor liable forfailures if it finds quality-related failures at a contractor.
 
 
While the guidance is not legally binding, when it isfinalized, it will represent FDA's current thinking, and the FDA would like allparties involved to share this "current thinking." Comments on the guidance maybe submitted to the FDA until July 29.
 
 
 

Lori Lesko

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