Many drug manufacturers (owners) outsource different parts of manufacturing operations to bring products to market faster and at reduced costs. Outsourcing involves hiring a second party under a contract to perform the operational processes that are part of a manufacturer’s (Owner or sponsor) inherent responsibilities (as per FDA guidance). It is often heard from the sponsors that we don’t have a procedure because we delegated it to our CMO (A contract manufacturer). You cannot delegate your role as a sponsor to CMO. As per FDA regulations, “When a manufacturer uses a contract facility, the manufacturer’s quality unit is legally responsible for approving or rejecting drug products manufactured by contracted facilities, including for final release. The regulations require that quality unit’s responsibilities and procedures be in writing and that they be followed.” Each party engaged in drug manufacturing is responsible for ensuring cGMP compliance. The sponsor ensures compliance by providing oversight and the Contracted facility ensures compliance by complying with relevant cGMP practices and regulations.
In some cases, outsourcing could be complex because multiple contract facilities may be involved in the manufacturing of a single product. In that case, communication between different contractors is critical and also increases the complexity of oversight to be provided by the sponsor.
The sponsor should ensure that a contract manufacturer is qualified before signing a contract. Outsourced models require written Quality agreements that detail the product and services provided, responsibilities of both parties, quality specifications, and a communication mechanism between the owner and contracted facility.
For example:
- How will you approve changes to master batch records?
- How will you assess the regulatory impact of CMO-initiated changes?
- How will you disposition batches?
- How will you establish shelf-life and specifications?
- How will you oversee deviations and assess the impact on product quality?
- How would you communicate with each other?
- How will the owner audit for cGMP compliance?
Which Quality Systems are required for CMO oversight?
Depending on the phase of the product, different quality systems are required. For early phases, “fit-for-purpose” QMS is important while for commercial manufacturing fully developed, implemented, and integrated systems are required.
For Example:
- An internal system for Vendor qualification and routine auditing, where a risk assessment is done to identify high-risk CMO and low-risk CMO. High-risk CMO will require more monitoring as compared to low-risk CMO.
- An internal system for establishing and revising Quality Agreements.
- An internal system for computer system validation and data integrity.
- An internal system for change control to ensure that internal regulatory assessments are conducted when using your CMOs change control system to provide better oversight and management of changes.
- An internal CAPA system for Deviation/investigation /Complaints with an escalation process to include critical issues or adverse trends from CMOs. These risks should be managed through internal quality systems.
- An internal system for releasing and rejecting contract facilities products and services, including the final release. Contract facilities are also responsible for approving and rejecting products of their manufacturing operations.
- An internal system for Quality management for ongoing supplier monitoring to ensure all the quality trends related to suppliers and Internal quality systems are reviewed and monitored.