Quality Agreement Development and Importance

Supply Chain Management for Homeopathy, Part 3 of 4

By Tim Clarot, Industry Consultant

 

This third article in the supply chain management series will cover the development of a product owner-CMO Quality Agreement (QA) document. Beyond the regulatory requirement of having a documented Quality Agreement in-place, the creation of the document gives the owner an opportunity to evaluate each supply chain function and determine which tasks they are comfortable in sharing or delegating and the ones that they will maintain and control. FDA has created a guidance document (CPG), Contract Manufacturing Agreements for Drugs: Quality Agreements, https://www.fda.gov/media/86193/download, which provides a framework for delineation of supply chain responsibilities controlled by the owner and/or the CMO. A brief outline of some of the agency’s expectations are:

• Quality Unit (QU)—define how the parties will work together to ensure CGMPs
• Facilities and equipment—who set specifications for maintenance, validation, etc.
• Materials—who set specifications for raw materials, vendor selection and qualification, inventory management
• Product-specific items—operational requirements, expiration dating, validation
• Laboratory controls—validations, sampling protocols, testing timelines, out-of-specification (OOS) investigations
• Documentation, recordkeeping and change control—what changes require preauthorization by the owner

Specifically, FDA describes the owner/CMO relationship in the CPG:

“Each party engaged in the manufacture of a drug is responsible for ensuring compliance with CGMP for the manufacturing activities it performs.[1] ­For both owners and contract facilities that conduct manufacturing operations, CGMP ‘includes the implementation of oversight and controls over the manufacture of drugs to ensure quality, including managing the risk of and establishing the safety of raw materials, materials used in the manufacturing of drugs, and finished drug products.’[2] Drugs not manufactured in compliance with CGMP are adulterated.”[3]

Further, the CPG clearly states each QU’s responsibilities:

“In particular, this section of the quality agreement should be clear with respect to product release. Contract facilities are responsible for approving or rejecting the product or results of their manufacturing operations (e.g., test results, finished dosage forms, or in-process materials).[4] In addition, owners are responsible for approving or rejecting drugs manufactured by the contract facility,[5] including for final release. In all cases, the owner must not introduce or deliver into interstate commerce, or cause to be introduced or delivered into interstate commerce, any drugs that are adulterated or misbranded.”[6]

In addition to the specified elements of the quality agreement, it should also clarify and memorialize expectations. From the perspective of an owner, the document should include:

• The length and frequency of facility audits. For example, annual quality audits lasting two days.
• Required communication with timeframes. This should include owner contact names and method of contact. The type and timeframe of communication will vary based on the incident. You will want to know about a regulatory for-cause inspection immediately while other issues might not require the same sense of urgency.
• Documents needed for final product release with established turnaround time. Specifically state the documents you want to review before a batch is released and indicate the amount of time you will need to review the documents. Recognize that some releases will take longer than others based on the complexity of the process and the number of deviations that occurred during manufacturing.
• Recalls—never a pleasant topic but document how it will be conducted, initiated, and the roles of each organization.

Clearly, the creation of a quality agreement can be time-intensive. The best way to start is to create a matrix listing each step in your supply chain that will be outsourced. Create a table with the step in one column and your company and the CMO in adjacent columns. Identify the responsible party with a checkmark or describe the responsibility if it’s shared. An example of a quality agreement matrix is: