The velocity of innovation and competition in the life sciences is relentless. It’s prompting an increasing number of companies to adopt asset-light operational models that rely heavily on an ecosystem of contract manufacturing organizations (CMOs). As a result of this trend, the burden of meeting current good manufacturing practice (CGMP) guidelines is becoming more dispersed between the companies that own products and the contract facilities they depend upon. A sound quality agreement is the first step to ensuring that both parties are accountable and collaborating to meet regulations enforced by the U.S. Food and Drug Administration (FDA).
According to the FDA, a quality agreement is a comprehensive written agreement between parties involved in contract manufacturing that defines and establishes each party’s manufacturing activities in terms of CGMP compliance. The agreement should clearly state whether the owner or the contract facility (or both) carries out specific CGMP activities.(1)
The FDA’s current position on quality agreements is outlined in the “Contract Manufacturing Arrangements for Drugs: Quality Agreements” guidance published in 2016. The guidance explicitly states that manufacturing activities are the most important element of a quality agreement. It highlights the seven most critical areas that should be addressed in a quality agreement, and their specific impact of each in terms of quality and change control.
Collaboration is critical to any successful business partnership, so it’s important for owners and contractors to develop written and verbal communication protocols. A quality agreement should define all roles and manufacturing activities and establish appropriate contact personnel for each organization. Processes like corrective and preventive actions (CAPA) and deviations management have the potential to cause dissension, so responsibilities tied to investigations and other processes involving quality event management should be clearly delineated in the agreement. The guidelines also indicate that quality agreements should be clear with respect to product release.
An effective quality agreement identifies the specific site(s) where the contract facility will perform manufacturing operations, including specific services to be provided at each site.
A quality agreement should indicate which party will establish component specifications and which party will establish processes for auditing, qualifying and monitoring component suppliers. It should also identify who will conduct any testing or sampling required for compliance with CGMP.
A section of the agreement should address specific considerations pertaining to individual products. It should also designate how owners will transfer knowledge, such as product and process development information, to contract facilities to ensure manufacturing is aligned with CGMP.
If a separate contract laboratory is involved, all relevant roles and responsibilities should be defined. The quality agreement should explicitly state what data will be shared and how it will be disseminated.
In the FDA’s eyes, any activity that isn’t documented may as well not have happened. A quality agreement provides an opportunity for the contract facility and the owner to define expectations for who reviews and approves quality documents. It needs to describe protocols for making changes to standard operating procedures (SOPs), manufacturing records, specs, validation documentation, and any other essential documents related to products or services provided by the contract facility. Both parties’ roles in making and maintaining CGMP-compliant original documents or true copies should be specified. The agreement should also define how those records will be made readily available for inspection. It’s beneficial to include a statement indicating that electronic records will be stored in accordance with CGMP and maintained in a retrievable state throughout the requisite record-keeping time frames established in applicable regulations, per FDA requirements.
The guidance calls for owners to review and approve most changes before they are implemented. But in some circumstances, there are changes contractors may implement without notifying the owner. A quality agreement must outline how all these changes are made and managed.
A reasonably detailed quality agreement can help prevent assumptions that lead to compliance failures. However, while a quality agreement defines a project’s specific quality parameters and which parties are responsible for their execution, the level of detail will vary depending on the developmental stage of the project. At a minimum, a quality agreement should delineate each party’s obligations and responsibilities in the following baseline elements noted in the guidance:
In addition to detailing each of these facets, it’s prudent to also include formalized plans for communication, record availability and audits.
The FDA does not have specific guidelines for quality agreements between medical device companies and the CMOs that provide them with services. However, the FDA’s guidance asserts that quality agreements should address activities covered by 21 CFR Part 820, the Quality System Regulation (QSR) for medical device companies, “as applicable.” Given the inclusion of Part 820 in the guidance, a quality agreement between a medical device company and a CMO should address the following aspects to varying degrees, depending on the nature of the relationship between the two parties and the products and services involved:
To learn how the coordination of quality agreements and other contract manufacturing functions can be streamlined with digital tools, check out the “3 Ways Contract Manufacturing Organizations Are Looking to Digital Technology to Improve Collaboration” trend brief.
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