The recently issued FDA guidance for industry titled, “Con- tract Manufacturing Arrangements for Drugs: Quality Agreements,” (the “Quality Agreements Guidance”) states
that the FDA considers that the owner’s—those who own and
control a pharmaceutical material and engage the services of the
contract facilities—Quality Unit responsibility includes approving or rejecting the contract facility’s product or service —parties
that provide services on behalf of an owner. The services that can
be outsourced to a contract facility can be varied: formulation, fill
and finish, chemical synthesis, analytical testing, packaging and
However, all such activities are critical to the quality and efficacy of the final product and the owner, when approving a
contract facility, must ensure that the contract facility adheres
to cGMP requirements. Indeed, within the Quality Agreements
Guidance, it states that it is both the owner’s and contract facility’s responsibility to ensure compliance with cGMP for a drug
product manufacturing operation, otherwise, a drug product may
be considered to be adulterated.
With the FDA issuing the Quality Agreement Guidance, there
is recognition by the FDA that owners routinely utilize the services of contract facilities for various critical activities of drug manufacturing and that a critical tool to ensure a successful relationship between the owner and the contract facility is the Quality
Agreement. As part of a comprehensive quality systems model,
the owner should utilize a written quality agreement whenever
engaging the services of a contract facility so that it is clear the respective cGMP related roles/responsibilities between the owner
and contract facility for the services to be provided.
The quality agreement should clearly describe the materials
or services to be provided, quality specifications and define the
communication mechanisms between owner and contract facility. The quality agreement should address items that have a potential to impact the quality of the contract facilities deliverable,
such as: subcontracting by the contract facility; and addressing
change to processes, equipment, methods, specification, records/
data, etc. The FDA considers the quality agreement to be key in
facilitating compliance with cGMP to those matters relating to 21
CFR 211.22, which states that quality unit activities and procedures should be in writing.
The Quality Agreements Guidance builds upon ICH guid-
ance titled, “Q10 Pharmaceutical Quality System,” which states
that the owner is ultimately responsible for ensuring that“pro-
cesses are in place to assure the control of outsourced activi-
ties and the quality of purchased material.” Risk management
should be considered by the owner when approving a contract
facility and when compiling the quality agreement. The FDA
encourages both parties to utilize the concepts described in
ICH guidance titled, “Q9 Quality Risk Management,” to ensure
the most critical areas with the greatest potential impact to the
drug product or active pharmaceutical ingredient are consid-
ered during contract facility approval and quality agreement
implementation. When qualifying a potential contract facility,
the owner must assess the suitability and competence via on-
site audits—or other pre-defined qualification criteria—and
continually assess the performance of“approved” contract fa-
cilities against pre-defined criteria, which, in turn, is driven by
the quality needs of the outsourced activities.
The primary goal of the quality agreement is to define between
the owner or contract facility who has what cGMP responsibility
in relation to those applicable CFR requirements such as 21 CFR
parts 210, 211, 600-680, 820 and 1271. The Quality Agreements
Guidance defines the elements of a quality agreement within
the following sections: purpose/scope; definitions; resolution of
disagreements; manufacturing activities and document lifecycle.
The bulk of the quality agreement will specify the roles and responsibilities for the manufacturing and testing activities—the
owner outsourced services—which is the most critical element of
the quality agreement. It is imperative that the quality agreement
clearly specifies which party is responsible for the specific activity
and depending upon the nature of the outsourced activity will
cover the following topics.
QUALITY UNIT ACTIVITIES
Within the quality agreement relating to quality activities, it
should be clear how the owner and contract facility’s individual
Paul Mason, Ph.D.
Director of Lachman Consultant Services, Inc.
FDA’s Quality Agreements Guidance
Evaluation of FDA’s recently issued Contract Manufacturing Arrangements for Drugs:
Quality Agreements Guidance for Industry