Since the publication of ICH Q9 “Quality Risk Management,” applying the principles of Quality Risk Management (QRM) as part of Pharmaceutical Quality Systems is an expectation of global regulatory agencies. The effective application of QRM requires a significant degree of planning and preparation. This blog article discusses the integration of QRM into the planning process for Commissioning and Qualification (C&Q) of “Direct Impact” pharmaceutical and biopharmaceutical facilities and equipment systems.

In 2001, ISPE published “Baseline Guide 5 – Commissioning and Qualification”, which proposed a systematic mechanism called “Impact Assessment” to determine if an equipment system was GMP-relevant and had the potential to directly impact product quality. This seminal risk-management document preceded ICH Q9 publication by four years and began the “science-and-risk-based approach” to Equipment Validation and Qualification. The science-and-risk-based approach is summed by this ICH Q9 core principle: “The level of effort, formality and documentation of the quality risk management process should be commensurate with the level of risk”.  Because not all facilities or systems impact product quality and not all aspects of design and function are equally critical, risk identification and prioritization are required to implement ICH Q9 QRM principles in the planning of C&Q activities.

Here we outline the steps to applying QRM in C&Q planning:

Initiating the C&Q process:

  1. Identify a team of Subject Matter Experts (SMEs) familiar and knowledgeable about both the equipment or facilities and their intended uses/functions and the manufacturing process to be supported.
  2. Define and document the description of the change, the scope of work, and the reason and justification for change(s). Most pharmaceutical manufacturing organizations will already have an established process for such changes, including the designation of required approvers.

For each system involved with the planned change:

  1. Perform a preliminary screening for potential quality impact using high-level tools such as a Preliminary Hazards Analysis (PHA), ISPE System Impact Assessment, or a similar documented methodology. Changes or systems that have little or no quality impact potential should not require formal Qualification.
  2. For systems with “Direct Impact,” select an appropriate risk assessment tool (e.g., FMEA) to identify specific failure modes and the necessary risk mitigations or controls.
  3. The controls and mitigations based on engineering design aspects, for example, alarms and interlocks, are the “Critical Aspects” and must be demonstrated and documented (verified) as being present and operating as designed in the installed and operational system. The Critical Aspects should be documented and approved by the Quality unit and designated SMEs.

For complicated, multi-system projects:

  1. An overarching C&Q Plan is recommended to consolidate the quality information regarding a C&Q project and answer the following questions if they do not already exist in the firm’s SOPs.
  2. Which Quality System (QS) requirements are applicable based on project definition and scope?
  3. What aspects of the new or modified facility or system require Qualification, and what is the rationale for any exclusions?
  4. Will the use of properly documented (GDP-compliant) commissioning work meet Qualification requirements in lieu of repeat testing against a pre-approved protocol?
  5. How will nonconformances be handled?
  6. What are change control rules during project execution? If they differ between “Project Change Control” and “Operational Change Control,” at what point do routine Operational Change Control rules re-apply?


  1. QRM must be used to accomplish C&Q and Validation Master Plan (VMP) planning to fully realize the Science-and-Risk-Based Approach advocated by U.S. FDA and many international regulatory agencies.
  2. Simple “screening” tools such as the ISPE Quality Impact System Assessment checklist can separate and identify systems with potential product quality impact from non-GMP systems such as environmental control, waste management, or non-GMP packaging equipment.
  3. Once you identify “Direct Impact” systems, standard risk assessment methodologies, such as Process Hazard Analysis, Fault Tree, and FMEA, can identify specific design and engineering- based risk controls required for each system, called “Critical Aspects” by ASTM E 2500.
  4. Critical Aspects for each system inform the design, specification, and testing. Also, Critical Aspects define the parameters for approved as Qualified for clinical or commercial use, and therefore must be included in protocols and comprehensive planning documents.

Find Experts

PSC Biotech® applies QRM to C&Q on every level. The risk-based assessment component is a cornerstone for PSC Biotech®. Our biggest asset to your C&Q process is consulting on QRM. We are more than technicians at your service by additionally bringing specific consulting for problems and complicated systems. Contact us to let us know what you need.

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