Integrating Quality Risk Management (QRM) into Commissioning and Qualification (C&Q) for Pharmaceutical Facilities

Since the publication of ICH Q9 “Quality Risk Management”, applying its principles within Pharmaceutical Quality Systems has become an essential expectation for global regulatory bodies. For pharmaceutical and biopharmaceutical organizations, the effective application of QRM requires thorough planning and preparation. This article will explore how QRM can be integrated into the planning process for the Commissioning and Qualification (C&Q) of “Direct Impact” pharmaceutical and biopharmaceutical equipment and systems.

Historical Context and Evolution of Quality Risk Management in C&Q

In 2001, the ISPE introduced the “Baseline Guide 5 – Commissioning and Qualification,” which proposed the “Impact Assessment” process to assess whether an equipment system is GMP-relevant and could directly impact product quality. This document, published four years before ICH Q9, laid the groundwork for the science-and-risk-based approach to Equipment Validation and Qualification. As articulated in ICH Q9, this approach emphasizes that “the level of effort, formality, and documentation of the quality risk management process should be commensurate with the level of risk.”

Since not all equipment or systems directly impact product quality, and not all aspects of design or function are equally critical, identifying and prioritizing risks is crucial in applying ICH Q9 principles effectively in the C&Q planning process.

How to Apply Quality Risk Management (QRM) in C&Q Planning

At BioBoston Consulting, we guide you through the essential steps in integrating QRM into your C&Q planningQuality Risk, ensuring a thorough and compliant approach to validation and qualification. Here is how to get started:

1. Initiate the C&Q Process: Assemble the Right Team

The first step is to assemble a team of Subject Matter Experts (SMEs) who possess deep knowledge of both the equipment or facilities in question and the manufacturing process they will support. These experts are integral in defining the scope of work and determining the appropriate risk-based approach.

2. Define and Document Changes

Clearly document the change, including its scope, justification, and objectives. Most pharmaceutical organizations already have established processes for change management, including designated approvers. Ensure these processes are aligned with the upcoming C&Q activities.

3. Preliminary Screening for Quality Impact

For each system involved in the change, conduct a preliminary screening to assess potential quality impacts. Tools like Preliminary Hazard Analysis (PHA) or the ISPE System Impact Assessment can be useful at this stage. Systems identified with minimal quality impact can often bypass formal qualification processes.

4. Risk Assessment for “Direct Impact” Systems

For systems that have a “Direct Impact” on product quality, apply advanced risk assessment tools like FMEA (Failure Modes and Effects Analysis). This step identifies failure modes and necessary risk mitigations to safeguard product quality.

5. Critical Aspects: Engineering Controls & Documentation

Once the risks are identified, focus on the Critical Aspects of the system—key engineering controls like alarms, interlocks, and other safety measures that ensure product quality is protected. These Critical Aspects must be verified and documented, ensuring they are operational as designed in the installed system. Quality units and designated SMEs must approve these aspects.

6. Develop a Comprehensive C&Q Plan for Multi-System Projects

For complex or multi-system projects, creating an overarching C&Q Plan is advisable. This plan consolidates quality information and answers crucial questions, including:

Which Quality System (QS) requirements apply based on the scope of the project?

Which aspects of the new or modified system require qualification?

Can Good Documentation Practices (GDP)-compliant commissioning work replace formal qualification testing?

How will nonconformances be handled?

What are the rules for change control during project execution?

7. Establish Clear Protocols and Documentation

Ensure that all Critical Aspects are incorporated into the design, specifications, and testing protocols. These aspects will define the qualification parameters for the system, and proper documentation is required for approval and to meet regulatory standards for clinical and commercial use.

Summary: The Science-and-Risk-Based Approach to C&Q

In the world of pharmaceuticals, biotechnology, and medical devices, integrating QRM into C&Q and Validation Master Plan (VMP) is critical to complying with FDA and international regulatory agencies. By applying risk-based tools like the ISPE Quality Impact System Assessment, you can easily identify systems that have the potential to impact product quality and separate them from non-GMP systems.

Once “Direct Impact” systems are identified, Process Hazard Analysis, Fault Tree Analysis, and FMEA allows you to address specific design and engineering-based risks. This methodology ensures that your Critical Aspects are thoroughly assessed and documented, laying the foundation for proper qualification and regulatory compliance.

Need Help with QRM Integration into C&Q Planning?

At BioBoston Consulting, we specialize in helping pharmaceutical and biopharmaceutical companies apply Quality Risk Management (QRM) principles effectively in their Commissioning and Qualification processes. Our team works with you to ensure that your C&Q planning is compliant, risk-based, and aligned with industry best practices.

Do you need expert guidance on applying QRM to your C&Q activities? Contact BioBoston Consulting today to discuss how we can support you in streamlining your validation processes, ensuring product quality, and meeting regulatory requirements.