1. In the pharmaceutical industry, companies follow strict regulatory standards to ensure their manufacturing facilities, systems, and equipment maintain high levels of quality, safety, and effectiveness.

   The ISPE Baseline® Pharmaceutical Engineering Guide Volume 5: Commissioning and Qualification (ISPE, 2007) acts as a best practice framework that aligns engineering and quality expectations throughout the lifecycle of facility and system development. Notably, it plays a key role in helping teams achieve compliance with current Good Manufacturing Practices (cGMP) while also supporting timely and cost-effective project delivery.

   This summary critically appraises the ISPE C&Q Guide for Pharmaceutical Facilities, focusing on its methodology, core principles, and strategic impact in harmonising commissioning (C) and qualification (Q) practices across pharmaceutical environments.

   Introduction and Rationale

2. Volume 5 of the ISPE Essential Guide was developed to address recurring inefficiencies in pharmaceutical capital projects. These include duplicated engineering and verification efforts, unclear roles between quality assurance and engineering teams, and frequent delays in bringing new facilities into GMP operations.

   To tackle these challenges, the ISPE C&Q Guide for Pharmaceutical Facilities introduces a science- and risk-based framework that streamlines commissioning and qualification (C&Q) activities. This framework ensures that actions are value-adding, verifiable, and compliant with regulatory expectations such as those outlined by the US FDA, EU GMPs, and ICH guidelines (ISPE, 2007, p. 3).

   In contrast to traditional methods—where companies perform recruitment and qualification separately—Volume 5 promotes integration and cross-documentation. Consequently, this reduces the burden of duplicate testing and documentation, leading to a lifecycle-oriented approach that enhances compliance and operational performance.

   Scope and Applicability

3. The ISPE designed this guideline for globally regulated facilities, especially those involved in manufacturing active pharmaceutical ingredients (APIs), drug products, and biologics. It applies equally to new construction projects, facility modifications, and system upgrades.

   Although Volume 5 does not directly address process validation, it outlines the prerequisite activities necessary for successful execution. In doing so, it positions commissioning and qualification as foundational elements within the compliance lifecycle (ISPE, 2007, p. 5).

   Importantly, the ISPE C&Q Guide for Pharmaceutical Facilities does not serve as a regulatory requirement. However, regulators across the industry widely accept it due to its structured methodology and alignment with quality risk management principles (ISPE, 2007, p. 6).

   Classification of Systems and Risk-Based Approach

A cornerstone of the guideline is the classification of systems based on their potential impact on product quality. The risk-based approach divides systems into three primary categories:

• Direct Impact Systems: These have a direct influence on product quality, safety, or efficacy (e.g., purified water systems, clean utilities, sterilisation systems). Such systems require both commissioning under Good Engineering Practices (GEP) and formal qualification (ISPE, 2007, p. 14).
• Indirect Impact Systems: These support the operation of direct impact systems but do not directly influence product quality (e.g., chilled water, HVAC for non-GMP spaces). They are managed under GEP alone.
• No Impact Systems: These have no effect on product or regulatory outcomes (e.g., office lighting, standard air conditioning in non-GMP areas) and are excluded from qualification.

This classification supports resource efficiency by focusing qualification efforts where they matter most—on direct impact systems and their critical components (Khinast et al., 2021, p. 12).

4. Good Engineering Practice (GEP)

GEP is the foundation upon which commissioning is built. It encompasses industry-standard engineering, design, installation, and testing methodologies that ensure systems are fit for purpose. GEP-based commissioning verifies basic performance, safety, and functionality of systems before more formal qualification is performed.

According to ISPE (2007, p. 20), GEP includes accurate documentation, adherence to specifications, change management, calibration, and standard operating procedures (SOPs). Importantly, GEP reduces the burden of qualification testing by ensuring that most installation and operational checks are completed during commissioning.

5. The V-Model Framework

The guide adopts the V-Model to visualise the traceability between system requirements and corresponding verification activities. The left leg of the V represents requirement development (User Requirements Specification (URS), Functional Requirements Specification (FRS), and Design Specification (DS)), while the right leg represents verification (Installation Qualification (IQ), Operational Qualification (OQ), and Performance Qualification (PQ)).

This model enforces traceability and control, ensuring that every design element has a corresponding test or verification point. For example, a requirement for HEPA filter integrity in a cleanroom will have a design element and an OQ test to verify airflow and pressure differentials (ISPE, 2007, p. 27).

6. Commissioning and Qualification Process

6.1 Commissioning

Commissioning is defined as a systematic process of ensuring that all facility systems are designed, installed, tested, and capable of being operated and maintained according to the owner’s requirements and regulatory expectations (ISPE, 2007, p. 31). It includes:

• Physical completion
• Inspection and verification
• Start-up testing
• Adjustment and tuning
• System turnover documentation

Commissioning also includes functional tests that serve as the basis for later qualification, such as verifying that valves open correctly or that temperature sensors read within specified ranges.

6.2 Qualification

Qualification activities are executed only on direct impact systems and their critical components. The guide breaks qualification into:

• IQ (Installation Qualification): Verifies that systems are installed according to design documents and manufacturer specifications.
• OQ (Operational Qualification): Confirms that the system performs as intended under all anticipated operating ranges.
• PQ (Performance Qualification): Demonstrates system performance under simulated or actual production conditions.

Qualification documents must be approved by QA and executed by trained personnel. Where possible, testing conducted during commissioning can be leveraged for qualification purposes if it meets predefined acceptance criteria and documentation standards (FDA, 2011, p. 8).

7. Impact and Component Criticality Assessments

The guide emphasises early identification of system impact and component criticality to guide qualification efforts. Systems with direct impact are further analysed to identify critical components (e.g., pressure sensors, control valves) whose failure would compromise quality. Only these components undergo enhanced qualification scrutiny.

Component criticality assessment follows a documented rationale based on criteria such as whether the component directly controls or monitors critical process parameters (ISPE, 2007, p. 35). This granular level of control ensures that efforts are focused on areas of genuine risk.

8. Enhanced Design Review (EDR)

The ISPE guide recommends—but does not mandate—Enhanced Design Review (EDR) as a proactive step in identifying potential design flaws and regulatory gaps early in the project lifecycle. EDR brings together cross-functional stakeholders (engineering, QA, operations, validation) to assess design documents for GMP compliance and operational feasibility.

According to Reiche et al. (2022), EDR improves outcomes by anticipating failure modes and correcting them before procurement and construction begin. This enhances both cost control and regulatory readiness.

9. Documentation and QA Oversight

One of the most significant contributions of the ISPE guide is its emphasis on integrated and streamlined documentation. Key documents include:

• Validation Master Plan (VMP)
• Impact Assessment Reports
• Traceability Matrices
• Commissioning Protocols
• Qualification Protocols (IQ, OQ, PQ)
• Summary Reports

QA has an oversight role, particularly for qualification activities, ensuring that documents meet internal standards and regulatory requirements. They also manage deviation handling, change control, and the final acceptance for GMP operation (ISPE, 2007, p. 42).

10. Lifecycle and Continuous Improvement

The ISPE guide promotes a lifecycle approach to C&Q, whereby systems are designed, commissioned, qualified, operated, and maintained in a continuous feedback loop. Post-qualification, systems must be managed via a maintenance and calibration programme and subject to change control to preserve their qualified state.

This aligns with ICH Q8–Q10 expectations for a product lifecycle approach, emphasising continuous improvement and ongoing risk assessment (ICH, 2009).

Conclusion

ISPE Baseline Guide Volume 5 provides a structured, risk-based, and quality-focused framework for commissioning and qualification within the pharmaceutical sector. By advocating system impact assessments, leveraging GEP, and integrating commissioning with qualification, the guide enables facilities to be brought into compliant operation faster and more cost-effectively.

Its alignment with cGMP, ICH Q9 quality risk management, and FDA’s modern validation guidance renders it a cornerstone of engineering and compliance strategy in contemporary pharmaceutical manufacturing. As the industry increasingly moves toward science-based, data-driven quality systems, ISPE Volume 5 remains a vital reference for ensuring robust, compliant, and efficient project execution.

References

FDA (2011). Guidance for Industry: Process Validation – General Principles and Practices. [online] U.S. Food and Drug Administration. Available at: https://www.fda.gov/media/71021/download [Accessed 2 Aug. 2025].

ICH (2009). ICH Q10: Pharmaceutical Quality System. International Conference on Harmonisation. [online] Available at: https://www.ich.org/page/quality-guidelines [Accessed 2 Aug. 2025].

ISPE (2007). ISPE Baseline® Pharmaceutical Engineering Guide Volume 5: Commissioning and Qualification. 1st ed. Tampa, FL: International Society for Pharmaceutical Engineering.

Khinast, J., Rainer, M., Sacher, S. and Kaufmann, C. (2021). Risk-based Qualification Strategies in GMP Manufacturing. Journal of Validation Technology, 27(2), pp.10–17.

Reiche, M., Thiel, W., and D’Angelo, J. (2022). Enhanced Design Review and Early GMP Compliance in Facility Projects. Pharmaceutical Engineering, 42(3), pp.28–35.