The relentless pace of innovation and competition in the life sciences industry has led many companies to adopt asset-light operational models and increase their reliance on contract manufacturing organisation (CMO) partners. As this trend continues, it becomes crucial for both CMOs and the parent organisations that contract with them to ensure compliance with the current good manufacturing practice (cGMP) guidelines enforced by the U.S. Food and Drug Administration (FDA).

CMO Quality Agreement Definition

In the eyes of the FDA, a CMO quality agreement is a comprehensive written agreement between contracting parties that establishes and defines each party's manufacturing activities and their compliance with cGMP. It clarifies whether the product owner or the contract facility, or both, will carry out specific cGMP activities.¹

7 Quality Agreement Essentials

To create an effective CMO quality agreement, there are seven essential elements that must be addressed, as outlined in the FDA's "Contract Manufacturing Arrangements for Drugs: Quality Agreements" guidance. The key aspects of an effective CMO quality agreement are:

1. The activities of each party’s quality units:

Clearly defining roles, responsibilities, and communication protocols ensures smooth collaboration and effective contract manufacturing management. Areas like corrective action/preventive action (CAPA) and quality event management should be specifically addressed in the CMO quality agreement, along with product release protocols.

2. Facilities and equipment:

Identifying the specific sites where cGMP contract manufacturing operations will take place and the services provided at each site is crucial.

3. Materials management:

Quality agreements should specify which party will establish component specifications, auditing processes, and monitoring of component suppliers, and also determine responsibilities for testing and sampling required for cGMP contract manufacturing compliance.

4. Product-specific considerations:

A section of the CMO quality agreement should address any product-specific requirements, including the transfer of knowledge from owners to contract facilities to ensure alignment with cGMP contract manufacturing requirements.

5. Laboratory controls:

If a separate contract laboratory is involved, all relevant roles and responsibilities should be defined in the CMO quality agreement. It should also explicitly state what data will be shared and how it will be disseminated.

6. Documentation:

Your CMO quality agreement should emphasise the importance of documentation and establishing expectations for reviews, approvals, and change control protocols for essential documents related to products or services.

7. Change control associated with manufacturing activities:

The FDA’s cGMP contract manufacturing guidance states that a CMO quality agreement should outline how changes will be made and managed, with owners reviewing and approving most changes, while contractors may implement certain changes without prior notification.

How Extensive Should a CMO Quality Agreement Be?

The level of detail expressed in a CMO quality agreement may vary depending on the developmental stage of the project. At very least, it should delineate each party’s obligations and responsibilities in relation to the following baseline contract manufacturing management aspects noted in the guidance:

• The purpose and scope of the CMO quality agreement.
• The life cycle of, and revisions to, the agreement (i.e., effective date, termination, etc.).
• The resolution of disagreements.
• Definitions of terms. As markets continue to expand globally, the terminologies used by your expanding ecosystem of partners may become blurred. Both parties need to agree on the specific terminology to be used in their CMO quality agreement. For instance, a document that a company may call a production record may be referred to as a “traveler” by a contracting vendor that may use that term in other medical device contract manufacturing agreements. To ensure that contract manufacturing management practices remain effective, both organisations need consensus on which term will be used in their agreement.
• Manufacturing activities (i.e., responsibilities, documentation methods, approach to change control and revisions, etc.).

In addition to detailing each of these facets, it’s also wise to include formal plans for communication, record availability and audits in your CMO quality agreement.

CMO Quality Agreements for Medical Device Companies

When it comes to CMO quality agreements for medical device companies, the FDA does not provide specific guidelines. However, a medical device contract manufacturing agreement should address activities covered in the Quality System Regulation (QSR) in 21 CFR Part 820. This includes aspects such as quality system requirements, design controls, document controls, purchasing controls, production and process controls, and more, depending on the nature of the relationship and the products and services involved.

Continue Learning About CMO Quality Agreements

To learn more about how contract manufacturing software can streamline the coordination of quality agreements and other contract manufacturing management functions, the industry brief “Overcoming 3 Key Challenges Facing Life Science Contract Manufacturers” provides valuable insights.

References

1. “Contract Manufacturing Arrangements for Drugs: Quality Agreements,” Guidance for Industry, Nov. 2016.