Regulatory agencies have continually continued to make it clear that when a Contract Manufacturing Organization (CMO) or Contract Research Organization (CRO) experiences a deviation, the sponsor/Marketing Authorization Holder (MAH) has several key responsibilities:

1. Review the deviation: The sponsor must thoroughly review the deviation to ensure it was appropriately defined and investigated. This review is crucial as the sponsor cannot delegate their responsibility to ensure the drug product is safe, effective, and conforms to specifications and regulatory commitments.
2. Assess product impact: The sponsor should ensure that the CMO has properly assessed the impact of the deviation on the product. This includes evaluating whether the deviation affected material quality, safety, or efficacy.
3. Verify appropriate material control: It’s the sponsor’s responsibility to ensure the CMO has appropriately controlled the affected material and extended this control to any other potentially affected materials.
4. Make disposition decisions: Ultimately, the sponsor is responsible for deciding whether the product should be released, reprocessed, or rejected. This decision is especially critical if the deviation affected material in clinical trials.
5. Oversee corrective and preventive actions: The sponsor should understand how the CMO’s corrective and preventive action (CAPA) system operates and ensure appropriate measures are taken to prevent recurrence of the deviation.
6. Maintain oversight: While the quality agreement defines the CMO’s responsibilities, the sponsor retains 100% oversight, including executed batch record review, change control, and deviation review and approval.
7. Risk-based approach: For major or critical deviations, sponsors should employ a risk-based approach to assess the severity and potential impact.

To simplify the deviation notification process with a Contract Organization (CxO), sponsors and can implement several strategies:

Clear Communication and Documentation

1. Establish a Well-Defined Quality Agreement: Create a comprehensive quality agreement that clearly outlines the deviation notification process, including timelines, classification criteria, and reporting requirements.
2. Implement Standardized Templates: Develop and provide standardized templates for deviation reporting to ensure consistency and completeness of information.
3. Set Clear Notification Timelines: Agree on specific timelines for different deviation categories. For example, critical and major deviations should be reported within one business day.

Risk-Based Approach

1. Adopt a Quality Risk Management (QRM) Mindset: Approach the partnership with a focus on risk management, ensuring that both parties understand the potential impact of deviations on product quality and patient safety.
2. Calibrate Risk Classification: Align the deviation classification system between the sponsor and CxO to avoid discrepancies in severity assessment.

Streamlined Processes

1. Utilize Electronic Quality Management Systems: Implement digital tools to facilitate real-time reporting and tracking of deviations, improving efficiency and transparency. Yes, the sponsor should be taking a risk based approach to tracking deviations in their eQMS that captures the important sponsor/MAH decision making.
2. Define Clear Roles and Responsibilities: Clearly delineate who is responsible for each step of the deviation management process, from identification to reporting and investigation.

Training and Support

1. Provide Comprehensive Training: Ensure that CxO staff are well-trained on the sponsor’s quality expectations, deviation reporting procedures, and the use of any specific tools or systems.
2. Offer Ongoing Support: Establish a dedicated point of contact or support team to assist the CxO with questions or issues related to deviation reporting.

Regular Review and Improvement

1. Conduct Periodic Reviews: Schedule regular meetings to review the deviation notification process, discuss any challenges, and identify areas for improvement.
2. Encourage Open Dialogue: Foster an environment where the CMO feels comfortable reporting issues promptly without fear of punitive action.

I strongly believe that a CxO needs to implement these strategies (do not put it only on the MAH’s shoulders) as part of their client onboarding and management process to create a more efficient and effective deviation notification process. This approach not only simplifies the process but also ensures that critical quality information is communicated promptly and accurately, ultimately contributing to better product quality and regulatory compliance. Add some value and don’t make the sponsor beg for information.