Quality Agreements – PART 2
- From a cGMP perspective, manufacturing activities are the most important element in a quality agreement. The most critical pieces are quality and change control, as described in the following sections
2. Manufacturing Activities
a. Quality unit activities
Each party’s quality unit activities should be defined in detail how the
parties will work together to ensure compliance with cGMP.
Contract facilities are responsible for approving or rejecting the
product or results of their manufacturing operations.
Owners are responsible for approving or rejecting drugs
manufactured by the contract facility, including for final release.
It should describe how and when the owner and contract facility will
communicate with each other, both verbally and in writing.
Identifying appropriate contact personnel within the owner’s and
contract facility’s organization.
It covers audits, inspections, routine quality audits, cause audits.
and communication of findings.
The agreement should also set owner and contract facility expectations
regarding FDA inspections (pre-approval, routine surveillance, and
for-cause) with consideration for the nature of the products to be
manufactured and/or services to be provided.
It should include the parties’ agreed-upon provisions for
communicating inspection observations and findings, as well as
relevant FDA actions and correspondence.
The quality agreement should address when, how, and what
information the contractor will report to owners about objectionable
conditions observed during inspections and audits of the contract
b. Facilities and equipment
This section of a quality agreement should identify the specific site(s)
where the contract facility will perform manufacturing operations,
including the address of and specific services to be provided at each
It should indicate which party will be validating processes and
qualifying and maintaining equipment and applicable systems
relevant to the contracted operations.
These include information technology and automated control systems,
environmental monitoring and room classification, utilities, and any
other equipment and facilities that must be maintained to perform the
contracted manufacturing operations in compliance with cGMP.
The agreement also should identify which party will approve
equipment validation, qualification, and maintenance activities.
It should indicate how the parties will communicate information about
preventing cross-contamination and maintaining traceability when a
contract facility processes drugs for multiple owners.
c. Materials management
This section of a quality agreement should indicate which party will
establish specifications for components as well as which party will
establish processes for auditing, qualifying, and monitoring component
It should also identify which party will conduct required sampling and
testing in compliance with cGMP.
This section of the quality agreement should address how the parties
will ensure appropriate inventory management, including labeling,
label printing, inventory reconciliation, and product status
identification (e.g., quarantine).
The agreement should address how the contract facility will prevent
mix-ups and cross-contamination.
It should define each party’s roles in storage and transport — whether
from the contract facility back to the owner or to another contract
facility for further operations.
This includes defining activities for monitoring or validating shipping
conditions as appropriate.
d. Product-specific considerations
A comprehensive quality agreement may address specific
considerations related to individual products.
The owner and contract facility might opt to include this information
in an appendix, or directly in the body of the quality agreement.
In either case, if included, this section of the quality agreement should
include the parties’ expectations of each other regarding:
- Product/component specifications
- Defined manufacturing operations, including batch numbering processes
- Responsibilities for expiration/retest dating, storage and shipment, and lot disposition
- Responsibilities for process validation, including design, qualification, and ongoing verification and monitoring
- Provisions to allow owner personnel access to the contract facility when appropriate.
The quality agreement also should indicate how owners will transfer
knowledge, such as product and process development information, to
contract facilities and conversely how contract facilities should share
with owners product quality information gained throughout the
product life cycle.
e. Laboratory controls
The owner and contract facility should both have access to adequate
laboratory facilities for testing of their drugs.
We recommend the following elements:
- Procedures delineating controls over sampling and testing samples
- Protocols and procedures for communicating all laboratory test results conducted by contract facilities to the owner for evaluation and consideration in final product disposition decisions
- Procedures to verify that both owner and contract facilities accurately transfer development, qualification, and validation methods when an owner uses a contract facility for laboratory testing
- Routine auditing procedures to ensure that a contract facility’s laboratory equipment is qualified, calibrated, and maintained in a controlled state in accordance with CGMP
- Designation of responsibility for investigating deviations, discrepancies, failures, out-of specification results and out-of-trend results in the laboratory, and for sharing reports of such investigations
The quality agreement should define expectations between the contract
facility and the owner to review and approve documents.
It also should describe how changes may be made to standard
operating procedures, manufacturing records, specifications,
laboratory records, validation documentation, investigation records,
annual reports, and other documents related to products or services
provided by the contract facility.
The quality agreement should also define owners’ and contract
facilities’ roles in making and maintaining original documents or true
copies in accordance with cGMP.
It should explain how those records will be made readily available for
The quality agreement also should indicate that electronic records will
be stored in accordance with cGMP and will be immediately
retrievable during the required record-keeping time frames established
in applicable regulations.
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