Points to Consider When Applying QRM Principles to Better Manage Partnerships and Relationships with CMOs

Points to Consider When Applying QRM Principles to Better Manage Partnerships and Relationships with Contract Operations

Applying Quality Risk Management (QRM) principles in the pharmaceutical industry is critical for managing partnerships and relationships with Contract Development and Manufacturing Organizations (CDMOs), suppliers, and other external stakeholders. These relationships are more complex than traditional in-house operations due to the multiple parties involved and the risk of quality failures that can have far-reaching consequences. Below are key points to consider when applying QRM principles in contract operations.

1. QRM Is Not Optional — It’s a Regulatory Requirement

The FDA's FDASIA (2012) introduced significant changes to the definition of CGMP regulations, especially including oversight and managing risk as essential elements for ensuring drug quality. It is vital for all parties in the contract operation chain — the sponsor, CDMO, and supplier — to recognize that QRM is a regulatory requirement, not merely a best practice.

• Section 711 of FDASIA explicitly connects oversight and risk management with CGMP. This means that if an organization is not managing risk effectively, it may violate the law.
• Regulatory failures often result from poorly managed or unaddressed risks, underscoring the need for a structured QRM approach.

2. Understanding the Dynamics of Contract Operations: CDMO, Supplier, and Sponsor

In any contract operation, the roles of the CDMO, supplier, and sponsor are interconnected but distinct, with each party managing its risks and responsibilities.

• Supplier: Responsible for manufacturing materials that meet CGMP standards. They may supply multiple customers and thus must maintain internal standards that comply with global regulations.
• CDMO: This company takes on the responsibility of manufacturing finished drug products on behalf of the sponsor, typically under unique agreements and processes tailored to the sponsor’s needs.
• Sponsor: Must ensure that the CDMO and suppliers comply with CGMP and that quality is maintained throughout the product lifecycle.

The key to managing risks is ensuring alignment and clear communication among all parties. Tensions may arise when a regulatory risk occurs (e.g., a sponsor proposing a process that conflicts with CDMO’s internal standards). This dynamic requires proactive oversight and risk communication mechanisms.

3. The Importance of Quality Agreements

Quality Agreements are foundational in managing the relationship between the sponsor and the CDMO or supplier. These agreements should not be generic; they must specify clear roles, responsibilities, and risk management processes.

Key Considerations for Quality Agreements:

• Define QMS Responsibilities: Ensure each party’s role in the quality management system (QMS) is clearly outlined.
• Review and Evaluation: Include a provision for regular reviews and updates to the quality agreement to ensure it remains effective and responsive to evolving risks.
• Conflict Resolution: Establish mechanisms for resolving conflicts early in the process, reducing the risk of disruption.
• Dynamic Partnership: The quality agreement should set the foundation for a successful partnership that evolves into a strong relationship based on trust and mutual goals.

Quality agreements must be flexible enough to address the inherent risks of contract operations, particularly when unforeseen challenges arise.

4. Audit Programs: Are They Just a Ceremony?

Internal and external audits are crucial for identifying and managing risks in contract operations. However, audits are often perceived as a "ceremony" — a checkbox exercise rather than a meaningful risk assessment tool.

Key Points for Effective Audit Programs:

• Snapshot vs. Continuous Evaluation: A single audit is only a snapshot of a supplier or CDMO's compliance status. Effective risk management requires continuous, in-depth evaluation, not just a one-time check.
• Risk-Based Audit Approach: Instead of auditing based on routine schedules, audits should be risk-based and focused on areas where risk is most likely to occur (e.g., data integrity, aseptic processing).
• Auditor Expertise: The auditors must have sufficient expertise, especially when auditing complex areas like data governance or aseptic processing.
• Internal Audits: Don’t just rely on external audits; assess the effectiveness of internal audits at CDMOs or suppliers. An internal audit is often the first line of defence in identifying risks early.

An audit program should be comprehensive, ensuring that it proactively identifies risks and provides actionable insights that can improve operations.

5. Data Integrity and Governance: A Key Risk Area

Data integrity is one of the most critical areas of risk in pharmaceutical manufacturing today. The sponsor and CDMO must be vigilant about maintaining robust data governance practices.

• Historical Data Risks: Evaluate and manage the evolving risks of legacy systems and older data collection practices.
• Data Integrity Expectations: Implement controls for electronic and manual data to ensure that all generated data can be trusted, reviewed, and audited effectively.
• Flexibility in Risk Assessments: As data governance practices evolve, the risk assessments related to data integrity must also be flexible and adapt to new regulatory expectations.

Risk management strategies in this area must be dynamic and evolve to address the changing regulatory landscape around data integrity.

6. Effective Risk Communication: Avoiding the "Sugar-Coating" of Problems

Effective risk management is not just about identifying risks, but also about communicating them clearly and accurately within the organization. A common pitfall in many organizations is the tendency to downplay risks or misrepresent them as less critical than they truly are.

• Honest Communication: Management must foster a culture of transparency in which issues are discussed openly, and risks are acknowledged rather than hidden behind a "green" dashboard.
• Continuous Monitoring: Risk management isn’t a one-time effort; it requires continuous monitoring and a willingness to act when issues are identified, even when they might not be convenient.
• Management Review: A robust management review process is essential for ensuring that identified risks are addressed and mitigated promptly.

7. Building Collaborative Relationships with CDMOs and Suppliers

Partnerships with CDMOs and suppliers should be built on trust, mutual respect, and shared goals. A collaborative approach is essential to ensuring that risk management is effective.

Key Points for Effective Collaboration:

• Ongoing Dialogue: Foster continuous communication between the sponsor, CDMO, and supplier to identify and address risks early.
• Adaptation to Challenges: Both parties must be flexible and willing to adapt to changing circumstances, including evolving regulatory requirements or unforeseen operational challenges.
• Supportive Partnerships: The sponsor should not view the CDMO or supplier as merely a service provider but as a critical partner in ensuring drug product quality and regulatory compliance.

Building strong relationships will ensure better risk management and improve the overall quality and efficiency of the contract operation.

Conclusion: Continuous Improvement is Key to Managing Risk in Contract Operations

Managing risks effectively in contract operations is an ongoing effort. While quality agreements, audits, and risk assessments provide the framework, continuous review, adaptation, and collaboration between the sponsor, CDMO, and supplier are essential to long-term success. The pharmaceutical industry must learn from past enforcement actions and invest more resources into strengthening its risk management programs to reduce the likelihood of compliance failures. By maintaining open lines of communication, implementing risk-based audits, and fostering strong relationships, the risk of significant quality failures can be minimized, ensuring the safety and efficacy of drug products.

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