FDA Contract Manufacturing Guidance and EQMS

Quality Management - 1 February 2017

Recently published guidance from the FDA (Contract Manufacturing Arrangements for Drugs: Quality Agreements, November 2016) outlines their expectations and suggestions around contract manufacturing relationships and Quality Agreements.

In the simplest summary of this guidance, it suggests that the product owner and the contractor are jointly responsible for compliance. The responsibilities of each should be defined and assigned in a controlled document (the Quality Agreement). Despite the importance of this document, it cannot be used to delegate responsibility that must reside with each party, as stated in the guidance:

‘‘Implementing a written quality agreement can facilitate compliance with CGMP and, in particular, with 21 CFR 211.22(d), which states that quality unit activities and procedures should be in writing. FDA recommends that owners and contract facilities establish a written quality agreement to describe their respective CGMP-related roles, responsibilities, and activities in drug manufacturing. It is important to note that quality agreements cannot be used to delegate statutory or regulatory responsibilities to comply with CGMP.’’

‘‘Regardless of the format, a quality agreement should clearly document which party is responsible for specific activities. No party to a quality agreement may delegate any of its responsibilities to comply with CGMP.’’

"The owner needs to provide the technical and developmental information that ensures compliance with the product's regulatory filing, and the contractor needs to communicate relevant quality data and evidence of manufacturing control and quality control process compliance."

John Carkner

Sr. Consultant, SOLABS QA & Best Practices Unit

Understanding the joint responsibility, it is clear that a mechanism of communication needs to exist to serve the interests of both parties. The owner needs to provide the technical and developmental information that ensures compliance with the product’s regulatory filing, and the contractor needs to communicate relevant quality data and evidence of manufacturing control and quality control process compliance, specifically:

‘‘The quality agreement also should indicate how owners will transfer knowledge, such as product and process development information, to contract facilities to ensure a drug can be manufactured in compliance with CGMP, and conversely how contract facilities should share with owners product quality information gained throughout the product life cycle through the quality agreement or any other means.’’

‘‘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.’’

An Enterprise Quality Management System (EQMS) can be valuable in facilitating this communication and fulfilling the responsibilities of both parties. Controlled document management, change control, and capture and communication of OOS, complaint and CAPA resolution are all elements of the dialogue between owner and contractor, and all are well served by a capable EQMS system.

It is important to review the entire guidance to understand the broader context. As you read it, I encourage you to think of how an effective EQMS can support the requirements and keep the owner and contractor ahead of the curve in meeting regulatory expectations.

About the Author
John Carkner is Senior Consultant in SOLABS’ Quality Assurance & Best Practices Unit and has had a career spanning more than 35 years in the pharmaceutical industry. A microbiologist by training, he began his career in Quality Control with Pfizer Canada. John gradually took on more responsibility, including overall Quality for Pfizer’s Canadian manufacturing operations, eventually became Site Leader of their Arnprior, Ontario manufacturing site. When Pfizer divested the Arnprior site in 2009, John began a new phase of his career leading a contract manufacturing organization. He concluded his career as President and CEO of Pillar5 Pharma Inc., and after five years in contract manufacturing, moved to a less structured role as a consultant to the industry.