ISPE has just issued the 2nd Edition Baseline Guide for Commissioning and Qualification. The revised Guide will provide the pharmaceutical industry with a single source guidance document covering the elements required to apply quality risk management (QRM) and Quality by Design (QbD) to the application of commissioning and qualification (C&Q) for facilities, systems, and equipment. The Guide is specifically structured to meet the compliance expectations for Qualification (i.e., fit for intended purpose to support Process Validation (PV)). This edition will replace the original Guide issued in 2001, that introduced the impact assessment model for execution of C&Q and the lifecycle C&Q execution testing approach to leverage commissioning testing to meet compliance requirements for qualification.  In addition, the revised Guide will also replace the two, quality risk management-based guidance documents, applying the principles of ASTM E2500, issued in 2011.

Why is this Guide important to my organization?

Key drivers for the adoption of QRM to the C&Q process are clearly stated in the FDA Process Validation Guidance and the EU Annex 15 guidance documents. In addressing the requirements for Validation, these Regulatory Guidance’s state that the pharmaceutical industry should adopt the principles of QRM to their rationales, as shown in the following examples:

  • EudraLex The Rules Governing Medicinal Products in the European Union, Volume 4, EU guidelines for Good Manufacturing Practice for Medicinal Products for Human and Veterinary Use, Annex 15, Qualification and Validation, 1 October 2015:
    • “It is a GMP requirement that manufacturers control the critical aspects of their particular operations through qualification and validation over the life cycle of the product and process”
    • “A quality risk management approach should be applied throughout the lifecycle of a medicinal product. As part of a quality risk management system, decisions on the scope and extent of qualification and validation should be based on a justified and documented risk assessment of the facilities, equipment, utilities and processes”
  • FDA Guidance for Industry, Process Validation: General Principles and Practices, January 2011, Revision 1:
    • “FDA encourages the use of modern pharmaceutical development concepts, quality risk management, and quality systems at all stages of the manufacturing process lifecycle”
    • “With a lifecycle approach to process validation that employs risk-based decision making throughout that lifecycle, the perception of criticality as a continuum rather than a binary state is more useful. All attributes and parameters should be evaluated in terms of their roles in the process and impact on the product or in-process material and reevaluated as new information becomes available. The degree of control over those attributes or parameters should be commensurate with their risk to the process and process output.  In other words, a higher degree of control is appropriate for attributes or parameters that pose a higher risk.  The Agency recognizes that terminology usage can vary and expects that each manufacturer will communicate the meaning and intent of its terminology and categorization to the Agency”.
    • “Qualification of utilities and equipment can be covered under individual plans or as part of an overall project plan. The plan should consider the requirements of use and can incorporate risk management to prioritize certain activities and to identify a level of effort in both the performance and documentation of qualification activities”.

How will this guide help my organization?

Over the last 18 years, since the introduction of ICH Q9 and QRM to the C&Q process, the pharmaceutical industry has struggled in its attempts to define and adopt an accepted and recognized implementation process that is compliant, efficient, and cost-effective.  The new Guide incorporates current industry best practices and combines them with the concepts included in the regulatory guidance. Key elements of focus in the new Guide include:

  • Emphasis on QbD and risks to product quality
  • Explanation of the Engineering Quality Process (EQP) to be integrated into the Quality Systems needed to support the risk-based C&Q effort
  • A defined QRM C&Q execution process flow
  • A comprehensive C&Q planning process that defines typical deliverables and associated approvals to provide the necessary quality oversight
  • Use of a Traceability Matrix as a tool to document traceability of CAs/CDEs to product quality impacting requirements during the C&Q process
  • Definition of Critical Design Elements (CDEs) that provide the focus for Qualification
  • Clarification of terminology associated with the integrated lifecycle C&Q process for Verification
  • A defined approach to preparing User Requirements Specifications (URS) that distinguish quality impacting requirements from general requirements
  • An efficient approach for System Risk Assessment (SRA) that recognizes risk controls incorporated in vendor equipment
  • A Design Review (DR) process that begins at the design phase concluding with a Design Qualification (DQ) used to focus the C&Q implementation effort
  • Identification of elements of the lifecycle Verification activities that maximize the use of vendor testing and minimization of testing repetition
  • Implementation of a Change Management Process that defines the handoff from Engineering Change Management to Quality Change Control
  • A Vendor Audit process to be used to maximize the use of vendor documentation
  • Defined requirements for good documentation practice requirements so that Good Engineering Practice (GEP) documents meet Good Manufacturing Practice (GMP) needs
  • A scalable Acceptance and Release (A&R) process that documents fit or intended use and maintenance of the qualified/validated state
  • A risk-based process for periodic review of systems and equipment

What is the value?

Application of the new Guide’s principles in developing Corporate and/or site QRM Based CQV Program will result in measured value and robust compliance. Among the benefits achieved will be:

  • Efficient use of resources and project schedule reduction through the application of GEP resulting in reduced issues and errors during and post construction and schedule and cost reduction
  • Focus of the qualification effort on CAs/CDEs through the application of System Risk Management resulting in reduced schedule for those items typically on the critical path
  • Establishment of appropriate Quality oversight by application of a systematic Design Review/Design Qualification process resulting in enhanced compliance and proper application of effort based on criticality
  • Minimization of redundant verification testing at project end with changes managed throughout the lifecycle resulting in reduced schedule for those items typically on the critical path.

How CAI Can Help

How significant is it to your success to deliver a large project four months earlier or to reduce periodic review to 50% of the current effort?

CAI currently has four authors that worked on the original ASTM E2500, published in 2007, and CAI also had two authors on ISPE Baseline Guide Volume 5 2nd Edition. CAI has executed multiple projects using a QRM-based integrated C&Q approach per the principles defined in ASTM E2500, ICH Q9, and the current ISPE Baseline Guide Volume 5, 2nd Edition. Leverage our experience to optimize your C&Q program and deliver your projects more quickly with increased compliance and reduced costs. Design Review is an essential GEP and an enabling process for QRM-based integrated C&Q. CAI can help you develop your GEPs and a QRM-based integrated C&Q approach using the latest industry practices.


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