Advancing Commissioning and Qualification (C&Q) Through Quality Risk Management

The QRM Addendum – C&Q Delivery Process responds directly to findings from industry surveys conducted in 2023 and 2024 by the ISPE Global C&Q Community of Practice. These surveys revealed a key challenge: inconsistent application of quality risk management (QRM) principles across organizations. While companies broadly adopt risk-based thinking, execution varies widely, particularly when linking system qualification to process performance qualification and performance qualification of utilities and facilities. This Guide provides a more structured approach aligned with global regulatory frameworks, including ICH Q8, Q9, Q10, and Q12.

A central theme of the Addendum is strengthening the relationship between key quality concepts:

• Critical quality attributes (CQAs) define the characteristics that ensure product quality.
• Critical process parameters (CPPs) are process variables that impact CQAs.
• Critical aspects represent the controls required to manage CPPs.
• Critical design elements (CDEs) are the engineered features that enable those controls.

By clearly linking these elements, organizations can establish a robust manufacturing process control strategy. This strategy translates product and process knowledge into practical engineering requirements, ensuring that systems are designed to consistently deliver quality outcomes.

Importantly, the Addendum reinforces that CPPs remain critical throughout the lifecycle—even if risks are mitigated through design or procedural controls. Risk reduction does not eliminate criticality; it ensures control.

Integrating QRM Into the C&Q Lifecycle

The QRM-based C&Q approach emphasizes a proactive and structured lifecycle:

1. User Requirements Specification: Defines what the system must achieve, focusing on product quality and regulatory needs rather than design details
2. System Classification: Identifies which systems have direct impact on product quality and require qualification
3. System Risk Assessment (SRA): Evaluates risks related to CPP control failure and identifies necessary mitigation measures
4. Design Review and Design Qualification: Ensure that risk controls are embedded into system design through CDEs.
5. Construction and Verification: Applies Good Engineering Practice (GEP) to deliver systems that meet intended use.

This lifecycle is iterative, allowing new knowledge to refine risk assessments and system requirements as projects progress.

Enhancing Risk Assessment Practices

One of the most valuable contributions of the Addendum is its clarification of risk assessment practices. Too often, organizations rely on traditional methods like component criticality or failure modes and effects analysis without fully connecting risks to CPP control. The Addendum shifts the focus toward process-driven risk assessment, ensuring that all risks are evaluated in the context of their impact on CQAs.

The SRA tool plays a central role, enabling teams to:

• Identify risks linked to CPP failure
• Evaluate existing design controls
• Define additional controls or procedural mitigations
• Establish an acceptable risk profile

This approach aligns directly with ICH Q9(R1), emphasizing risk identification, evaluation, control, and acceptance.

Strengthening Quality Systems Through the Engineering Quality Process (EQP)

A recurring theme throughout the Addendum is the importance of aligning C&Q with the site’s pharmaceutical quality system (PQS). The EQP concept promotes integration between engineering, quality assurance, and manufacturing functions. By embedding GEP into the PQS, organizations can confidently use engineering documentation and testing as part of qualification, reducing duplication and improving efficiency.

Beyond compliance, the benefits of a QRM-based C&Q approach are tangible. Companies that adopt these practices have reported faster project delivery, reduced rework, and more efficient qualification processes. This translates directly into faster access to life-saving therapies, helping address product shortages and meet patient needs.

The ISPE Baseline® Guide: Commissioning and Qualification (Second Edition) and its Addendum represent a significant evolution in how the pharmaceutical industry approaches system qualification. By anchoring C&Q in QRM, organizations can create a more efficient, science-based, and compliant process.

This Guide is aligned and can be used in conjunction with the ISPE Baseline Guide: Commissioning and Qualification (Second Edition), the ISPE Good Practice Guide: Good Engineering Practice (Second Edition), the ISPE Baseline® Guide: Water and Steam Systems (Third Edition), and ISPE GAMP® 5: A Risk-Based Approach to Compliant GxP Computerized Systems (Second Edition).

Learn more about the ISPE Baseline Guide: Commissioning and Qualification (Second Edition)