This is the fourth installment in PSC’s series on Quality Risk Management (QRM) in Commissioning and Qualification (C&Q). This follows on the concepts introduced in the first three installments: QRM in C&Q Planning, Risk Assessments – One Size Does Not Fit All, and Critical Aspects of Pharmaceutical Facilities and Equipment – Identification and Verification. This week’s article discusses where C&Q activities fit into the process validation lifecycle.


Validation of pharmaceutical manufacturing processes became a cGMP expectation in the early 1980s. For many years afterward, “Validation” consisted of two related but separated activities:

  1. Qualification of designated facilities, equipment, utilities, etc.
  2. Validation of manufacturing processes and supporting procedures such as equipment cleaning, sterilization of components, etc.

There are understood overlaps between the two activities, such as equipment requiring qualification prior to process validation runs. However, Qualification and Validation were usually the responsibility of separate, and often siloed, technical disciplines. Engineers and technicians qualified facilities and equipment. Afterward, process scientists and production operators ran process validation studies. Often, there were no formal mechanisms for communicating process requirements to design/project engineers or documented traceability to the Quality department for approval to implement the requirements.

ICH Q9 and the 2011 FDA Process Validation Guideline

In the last 10-15 years, a dramatic shift occurred in Qualification and Validation practices. Previously, many pharmaceutical industry practices were based on anecdotes, individual company experiences, and “precedent”. Since the 2007 publication of ICH Q9, and the FDA’s subsequent update of its 1987 Process Validation Guidance for Industry in 2011, updated Qualification and Validation practices have become known as “science and risk-based approaches”. These modern approaches utilize the well-established science of Quality Risk Management (QRM) as described by  of ICH Q9 Quality Risk Management.

Application of QRM principles has broad implications for all areas of GxP operations, including but not limited to:

    • Commissioning and Qualification (C&Q)
    • Process Validation (PV)
    • Corrective and Preventive Action (CAPA)
    • Preventative Maintenance
    • Instrument Calibration
    • Change Control
    • Training
    • Other
C&Q in Process Validation
In the arena of Process Validation, the FDA’s 2011 Guidance for Industry – Process Validation: General Principles and Practices integrated previous FDA process validation guidance with the QRM principles of ICH Q9 and established a three-stage “lifecycle” approach to achieving and maintaining a validated state. See the diagram for an overview of the Process Validation lifecycle. A validated state means a demonstrated and documented state of process control.

Specification, design, delivery and installation are part of the lifecycle, as is verification, or Commissioning and Qualification (C&Q). They are not C&Q itself, but prerequisite activities. The FDA Process Validation Guide designates C&Q as the first phase of Stage 2 Process Qualification, commonly referred to as “Stage 2a”. An ASTM Standard, ASTM E2500 Standard Guide for Specification, Design, and Verification of Pharmaceutical and Biopharmaceutical Manufacturing Systems and Equipment, details a risk-based approach to C&Q based on the ICH Q9 principles. The FDA Process Validation guidance suggests that the ASTM E2500 is “useful” in describing FDA’s expectations regarding how industry is to perform an activity in a science-and-risk-based manner compliant with ICH Q9.

These three documents: ICH Q9, FDA Process Validation Guideline, and ASTM E2500, will inform our further discussion of how C&Q fits into the overall Process Validation Lifecycle.

Where C&Q Fits Into the Validation Lifecycle

The diagram below depicts the 3-Stage FDA Process Validation Lifecycle with the activities and data of each stage or phase.

C&Q in Process Validation

QRM Implications for Facility and System Design – Critical Aspects

Process User Requirements are the specifications that facilities and equipment must satisfy to ensure their fitness for intended use, and are developed in Stage 1 Process Design. The functions, features, abilities, and performance characteristics necessary to ensure consistent product quality and patient safety are referred to by ASTM E2500 as Critical Aspects.  The ASTM further states that Verification (C&Q) activities should focus on these aspects of manufacturing systems, providing documented objective evidence of meeting predetermined test/inspection criteria. Check out our previous blog discussing the “how-to” of identifying Critical Aspects using risk assessment tools.

Summary and Conclusions

    • In the shift to risk-based Qualification and Validation processes, the functions and features of GMP-relevant facilities and equipment systems needed to ensure the quality and patient safety of a new or redesigned pharmaceutical product are identified as part of the “Process Design” Stage (Stage 1) of the FDA Process Validation Lifecycle.
    • Stage 1 development knowledge, data, and process experience are used to establish a specific set of Process User Requirements that help ensure product quality and patient safety.
    • Technical Subject Matter Experts (SMEs) perform a risk assessment to identify risks to meeting Process User Requirements from the manufacturing process and systems. SMEs also evaluate design solutions and risk control plans as they involve facility/system designs.
    • Critical Aspects of facility/system design are risk controls that are engineered functions and features of facilities and equipment designs.
    • Risk controls must be verified (through commissioning, qualification, or both) to be installed and operating per design for the facility/system to be considered fit-for-purpose.

Authored by: David Dolgin

Edited by: Crystal McClain, PhD

About PSC Biotech®

Outsourcing using PSC Biotech® Engineering consultants enables you to hire proficient and experienced engineers in Commisioning and Qualification on a project basis. PSC Biotech® has over 25 years of experience in C&Q consulting for life sciences companies and consultants available worldwide. PSC Biotech® Commissioning, Qualification, and Validation (CQV) Engineers are available to:

    • Installation and operational qualifications (IQ/OQ) for Building Management System (BMS) Systems and Environmental Monitoring Systems
    • Development and assessments for maintenance programs
    • Detailed Operational Qualifications
    • Process Validation (PV)
    • SOP development and preventative maintenance implementation
    • Turnover documentation package preparation
    • Compile the CQV Issues Log
    • Finalize the project with a CQV Summary Report (CQVSR)
    • … and more!

Contact us today for a tailored, budget-friendly, quote!

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