Global Regulatory Framework for Pharmaceutical Commissioning and Qualification

This report provides a comparative analysis of the regulatory frameworks for pharmaceutical equipment commissioning and qualification (C&Q) from the U.S. Food and Drug Administration (FDA), the European Medicines Agency (EMA), and the World Health Organization (WHO). It highlights a global trend towards harmonization driven by risk-management principles. Key distinctions are examined, including the EMA’s prescriptive, plan-centric approach with a mandatory Validation Master Plan (VMP) versus the FDA’s flexible, process-centric lifecycle model. The WHO's role in setting a foundational global standard is also detailed. The report further explores how industry standards like ASTM E2500-25 provide practical methods for implementing modern C&Q strategies.

Summary of Regulatory Guidance for Pharmaceutical Commissioning and Qualification

U.S. Food and Drug Administration (FDA)

• The FDA's framework is established in the Code of Federal Regulations, Title 21, Part 211 (21 CFR Part 211), which details the Current Good Manufacturing Practice (CGMP) for Finished Pharmaceuticals (1). These regulations set foundational requirements for the design, construction, maintenance, and suitability of buildings, facilities, and equipment, forming the legal basis for qualification activities (2).
• The FDA's 2011 "Guidance for Industry: Process Validation: General Principles and Practices" modernizes this framework by introducing a three-stage product lifecycle approach: Stage 1 (Process Design), Stage 2 (Process Qualification), and Stage 3 (Continued Process Verification) (3).
• Qualification of facilities, utilities, and equipment is a mandatory prerequisite and a fundamental component of Stage 2, Process Qualification. This stage confirms that the process design is capable of reproducible commercial manufacturing (4).
• While the terms Installation Qualification (IQ), Operational Qualification (OQ), and Performance Qualification (PQ) are not explicitly defined within 21 CFR Part 211, they are universally accepted industry conventions for generating the documented evidence required to demonstrate that equipment is fit for its intended use (5).
• The FDA's approach is performance-based, emphasizing the use of sound science and quality risk management (QRM) principles, as outlined in ICH Q9, to justify the scope and extent of validation activities. A Validation Master Plan (VMP) is not a specific regulatory requirement but is considered an industry best practice and is widely expected by investigators as evidence of a planned, controlled approach to validation (6, 7).

European Medicines Agency (EMA)

• The EMA's requirements are detailed in EudraLex Volume 4, Good Manufacturing Practice (GMP) Guidelines, with Annex 15: Qualification and Validation (revised in 2015) serving as the primary document (8).
• Annex 15 provides a more prescriptive and structured framework for C&Q compared to the FDA. It explicitly requires that all qualification and validation activities be planned and documented in a Validation Master Plan (VMP) or an equivalent document. The VMP must define the organization's validation policy, structure, and program (9).
• The guidance formally defines and mandates a sequential lifecycle approach to qualification, including User Requirements Specification (URS), Design Qualification (DQ), Factory/Site Acceptance Testing (FAT/SAT), Installation Qualification (IQ), Operational Qualification (OQ), and Performance Qualification (PQ) (9).
• The application of a QRM approach is a central and mandatory principle. Annex 15 states that decisions on the scope and extent of qualification and validation must be based on a "justified and documented risk assessment." Furthermore, the practice of retrospective validation is explicitly disallowed (9).

World Health Organization (WHO)

• The WHO provides globally recognized GMP guidelines that often form the basis for national regulations, particularly in emerging markets. The key document is the WHO Technical Report Series (TRS) 1019, Annex 3: "Good manufacturing practices: guidelines on validation," issued in 2019 (10).
• This guidance is harmonized with global regulatory trends, promoting a lifecycle approach to validation and the integration of qualification as a core component. It defines the standard qualification stages (DQ, IQ, OQ, PQ) and recommends a planned approach, typically documented in a VMP (10, 11).
• The WHO framework serves as a comprehensive set of principles and best practices for ensuring pharmaceutical quality. For multinational organizations, compliance with the more prescriptive EMA and FDA regulations generally ensures alignment with WHO principles (10).

The Foundational Principles of Commissioning and Qualification

Defining the Scope: Commissioning, Qualification, and Validation

In the pharmaceutical industry, the terms commissioning, qualification, and validation represent distinct yet interconnected activities essential for ensuring that manufacturing systems produce safe, effective, and high-quality medicinal products. A precise understanding of their definitions and relationships is fundamental to developing a compliant and efficient quality system.

Commissioning is a systematic, documented, and engineering-focused process. Its primary objective is to ensure that facilities, utilities, systems, and equipment are designed, installed, tested, operated, and maintained according to the design specifications and the user's requirements (12). Commissioning activities, such as Factory Acceptance Testing (FAT) and Site Acceptance Testing (SAT), are typically performed before formal GMP qualification. This process verifies that the system is ready for its intended operational use from an engineering perspective (5, 13).

Qualification is a formal, GMP-mandated process of demonstrating and documenting that facilities, utilities, and equipment are suitable for their intended purpose and function correctly (12, 13). It extends beyond commissioning to provide the objective evidence required by regulatory authorities. Qualification formally verifies that the equipment, as installed and operated, will not adversely impact the quality of the product (1).

Validation is a broader concept that encompasses qualification. The FDA defines process validation as "establishing documented evidence that provides a high degree of assurance that a specific process will consistently produce a product meeting its predetermined specifications and quality attributes" (1). Qualification of the equipment and utilities used within that process is therefore a critical prerequisite for successful process validation (5).

Historically, a rigid demarcation existed between commissioning as an "engineering" activity and qualification as a "compliance" activity. However, modern regulatory and industry thinking, influenced by principles of efficiency and risk management, has led to a significant integration of these functions. The traditional model often resulted in redundant testing and excessive documentation, as tests performed during commissioning were repeated during qualification (14). Contemporary approaches, particularly those outlined in industry standards, advocate for an integrated C&Q process. In this model, commissioning activities that are well-planned, well-documented, and executed to GMP standards can be leveraged to satisfy formal qualification requirements. This eliminates unnecessary repetition and focuses resources on the aspects most critical to product quality, reflecting a mature understanding that quality is built into a system from the design and installation phases onward, not merely tested at the conclusion (15, 16).

The Traditional Framework: IQ, OQ, and PQ

The traditional, sequential approach to equipment qualification is structured around three core phases that provide a logical, step-by-step method for generating documented evidence of suitability. Installation Qualification (IQ) provides documented verification that equipment is installed correctly according to design specifications (1, 5). Operational Qualification (OQ) follows, verifying that the installed equipment operates as intended throughout its defined operating ranges (5). Finally, Performance Qualification (PQ) demonstrates that the equipment, integrated into the manufacturing process, consistently performs as expected under real-world conditions (1).

The Influence of Modern Industry Standards

Regulators typically define what must be achieved (e.g., equipment must be suitable for use), while industry organizations often develop standards that detail how to achieve it. Two standards have been particularly influential in shaping modern C&Q practices.

ASTM E2500-25: A Science- and Risk-Based Verification Framework

The ASTM E2500 standard emerged from a collaboration between industry and regulators to address the inefficiencies and excessive paperwork of traditional qualification models (14). The newly revised ASTM E2500-25 reaffirms and expands upon a science- and risk-based approach that aligns system design directly with process control strategies to ensure product quality and patient safety from the project's inception (22).

A core concept of the standard is "verification," an umbrella term that replaces the rigid, sequential IQ/OQ/PQ model (23, 24). The goal is to provide documented evidence that a system is "fit for intended use" by performing the right tests at the right time, thereby avoiding redundant activities (24, 25). This is achieved through a proactive approach that designs quality into a system from the start by focusing on its relationship to the product's Critical Quality Attributes (CQAs) and the process's Critical Process Parameters (CPPs) (22).

Key updates and concepts in the 2025 revision include:

• Critical Design Elements (CDEs): The standard introduces CDEs, which are the features or functions of a manufacturing system essential for controlling CPPs (22). By identifying CDEs early through risk assessments, verification efforts can be focused on the system components that have the most significant impact on product quality (26).
• Formalization of Design Qualification (DQ): The revised standard formalizes DQ as a proactive tool used early in the project lifecycle. It serves to document risk mitigation strategies, formalize the acceptance of the system design, and provide a solid foundation for the subsequent verification plan (22, 27).
• Expanded Roles and Lifecycle Accountability: The role of the System Owner is defined as a key figure responsible for the system throughout its lifecycle, ensuring continuity, alignment, and communication from initial specification through to operation and change management (22).
• Integrated Verification: The standard promotes an integrated process where well-documented commissioning activities (like FAT and SAT), if verified by Subject Matter Experts (SMEs), can be used to directly support or replace redundant testing in formal verification protocols (22).

ISPE Baseline Guide 5: Implementing a Risk-Based Camp;Q Process

The International Society for Pharmaceutical Engineering (ISPE) Baseline Guide 5, Commissioning and Qualification (Second Edition), published in 2019, provides practical guidance for implementing a modern, risk-based C&Q process (16). This revision supersedes previous versions and aligns the ISPE's methodology with the principles of ASTM E2500 and ICH guidelines, aiming to create a compliant, efficient, and cost-effective approach (15).

The guide seeks to eliminate confusion over terminology by using "C&Q" to describe the process for establishing that facilities, systems, and equipment are fit for purpose, and "verification" to describe an activity performed during the C&Q process to establish suitability for intended use (15). A central tenet of the guide is a system classification approach based on risk:

• Direct Impact Systems: These are systems that have a direct impact on product quality. They require full commissioning and qualification and are the focus of formal System Risk Assessments (15).
• Not Direct Impact Systems: These systems do not have a direct impact on product quality and only require commissioning (15).

For Direct Impact systems, a System Risk Assessment (SRA) is used to identify risks to product quality and define the Critical Design Elements (CDEs)—the system features and functions that control those risks. The formal qualification effort is then focused on verifying these CDEs (15). Within this framework, commissioning verifies all design requirements outlined in the User Requirements Specification (URS), while qualification specifically verifies the CDEs identified in the risk assessment (15). The guide explicitly supports an integrated process where planned and well-documented commissioning tests can fulfill formal qualification requirements, a concept previously referred to as "leveraging" (15). By retiring the traditional V-model, the guide promotes a flexible, risk-based lifecycle approach that aligns with modern regulatory expectations (28).

A Comparative Analysis of Global Regulatory Frameworks

The U.S. Food and Drug Administration (FDA) Approach

The FDA's regulatory framework for equipment qualification is rooted in the CGMP regulations and modernized by its guidance on process validation, creating a system that is both foundational in its requirements and flexible in its implementation.

The legal basis for qualification is established in 21 CFR Part 211. Specifically, Subpart C, "Buildings and Facilities," and Subpart D, "Equipment," mandate the fundamental state required for all manufacturing systems (17). Section 211.63 requires that equipment be of "appropriate design, adequate size, and suitably located to facilitate operations for its intended use and for its cleaning and maintenance" (18). Section 211.65 further stipulates that equipment surfaces in contact with product materials "shall not be reactive, additive, or absorptive so as to alter the safety, identity, strength, quality, or purity of the drug product" (18). These regulations define the required outcome—that equipment must be suitable for use—but do not prescribe the specific methodology for demonstrating this suitability.

This is where the FDA's 2011 "Guidance for Industry: Process Validation: General Principles and Practices" provides the modern context (3). This guidance reframed qualification from a series of discrete events into an integrated part of the product lifecycle.

• Stage 1 - Process Design: This initial stage involves building product and process knowledge to establish a strategy for process control. A key activity within this stage is the design of the facility and the initial qualification planning for utilities and equipment (4, 19).
• Stage 2 - Process Qualification: In this stage, the process design is evaluated to confirm its capability for reproducible commercial manufacturing. The FDA explicitly divides this stage into two parts: (1) Design of a Facility and Qualification of Utilities and Equipment, and (2) Process Performance Qualification (PPQ) (4, 19). This structure formally positions equipment qualification as a prerequisite for demonstrating process capability. The traditional PQ is a key component of the broader PPQ, which combines the qualified equipment, trained personnel, and commercial manufacturing process to produce test batches (13).
• Stage 3 - Continued Process Verification: This stage requires an ongoing program to collect and analyze process data, ensuring that the manufacturing process remains in a state of control throughout routine commercial production (13, 19).

A defining characteristic of the FDA's approach is its implicit endorsement of science- and risk-based methodologies. While the foundational regulations in 21 CFR Part 211 are prescriptive about the required state of equipment, the 2011 guidance is performance-based. It repeatedly aligns process validation activities with the principles of ICH Q8 (Pharmaceutical Development), ICH Q9 (Quality Risk Management), and ICH Q10 (Pharmaceutical Quality System) (3, 20). This was a deliberate policy evolution, signaling to the industry that while the fundamental CGMP requirements must be met, the methods used to demonstrate compliance should be justified by scientific understanding and documented risk assessment. This has allowed industry-developed standards, such as ASTM E2500, to become widely accepted methodologies for meeting FDA expectations, even though the regulations themselves do not use modern terms like "verification" or "risk-based qualification."

The European Medicines Agency (EMA) Approach

The EMA's framework for C&Q, detailed in EudraLex Volume 4, Annex 15: Qualification and Validation, is notably more prescriptive and structured than that of the FDA (8). This annex, which became operational in October 2015, provides a clear and detailed roadmap for manufacturers to follow throughout the lifecycle of their facilities, equipment, and processes (21).

A central pillar of the EMA's approach is the mandatory requirement for comprehensive planning. Annex 15 explicitly states that "All qualification and validation activities should be planned" and that the key elements of this planning should be documented in a Validation Master Plan (VMP) or an equivalent document (9). The VMP serves as a high-level summary of the company's overall validation philosophy and program. Annex 15 specifies that the VMP should include or reference, at a minimum: the validation policy, the organizational structure for validation activities, a summary of all facilities and systems and their validation status, change control procedures, and guidance on developing acceptance criteria (9). This requirement formalizes the planning process to a degree not explicitly seen in FDA regulations.

The EMA's guidance also mandates the application of Quality Risk Management (QRM). Annex 15 requires that "A quality risk management approach should be used for qualification and validation activities," and that any decisions regarding the scope and extent of these activities "should be based on a justified and documented risk assessment" (9). This elevates QRM from a recommended best practice to a required, auditable component of the validation system. The risk assessment must be a living document, repeated as necessary when changes occur or as process understanding increases (9).

Furthermore, Annex 15 provides clear definitions and expectations for a sequential, stage-gated qualification process that begins even before equipment is purchased. The defined stages include:

• User Requirements Specification (URS): Defining the requirements for the system.
• Design Qualification (DQ): Documented verification that the design of the system is suitable for the intended purpose.
• Factory Acceptance Testing (FAT) / Site Acceptance Testing (SAT): Testing at the vendor's site and/or upon receipt.
• Installation Qualification (IQ), Operational Qualification (OQ), and Performance Qualification (PQ): The traditional sequence of qualification activities, each with defined minimum requirements (9).

This structured, lifecycle approach, combined with the explicit mandates for a VMP and documented risk assessments, makes the EMA's framework one of the most detailed and rigorous among global regulators.

The World Health Organization (WHO) Approach

The WHO serves a critical role in establishing a global baseline for GMP, providing guidelines that are widely adopted by national regulatory authorities, especially in countries without their own extensive regulatory infrastructure. The primary document governing these activities is the WHO Technical Report Series (TRS) 1019, Annex 3: "Good manufacturing practices: guidelines on validation," published in 2019 (10).

The WHO's guidance is closely harmonized with the principles established by the FDA, EMA, and the International Council for Harmonisation (ICH). It advocates for a lifecycle approach to validation, where qualification is an integral part. The document provides clear definitions for the standard qualification stages, including Design Qualification (DQ), Installation Qualification (IQ), Operational Qualification (OQ), and Performance Qualification (PQ), mirroring the structure found in EMA's Annex 15 (10).

Similar to other major regulators, the WHO recommends a planned and systematic approach to validation. This is typically achieved through a Validation Master Plan (VMP), which is described as a high-level document that summarizes the manufacturer's overall philosophy, approach, and work program for establishing performance adequacy (11). While presented as a recommendation rather than a strict mandate, the VMP is positioned as a foundational element of a well-organized validation system (10).

The WHO's guidelines function as an international consensus on best practices. For a multinational pharmaceutical company, adhering to the more stringent and detailed requirements of the FDA and EMA will almost certainly ensure compliance with WHO principles. However, for manufacturers in regions that have adopted WHO guidelines as their national law, TRS 1019 provides a comprehensive and authoritative roadmap for implementing a quality system that is recognizable and acceptable to global regulatory bodies. It serves as both a foundational standard and a pathway toward global compliance.

Harmonization and Divergence: A Thematic Comparison

The Central Role of Quality Risk Management (QRM)

A powerful trend toward harmonization is the universal adoption of Quality Risk Management (QRM) principles, as detailed in ICH Q9. All three regulatory bodies have moved away from a one-size-fits-all validation approach, instead requiring that the scope, depth, and intensity of C&Q activities be proportional to the risk that a given system poses to product quality and patient safety.

• Convergence: The core principle is shared. The FDA's 2011 guidance promotes a science- and risk-based approach (3), the EMA's Annex 15 mandates it (9), and the WHO's TRS 1019 recommends it as a fundamental element of validation (10).
• Divergence: The primary difference lies in the explicitness of the requirement. The EMA is the most prescriptive, stating that the scope of validation must be justified through a "justified and documented risk assessment" (9). This makes the risk assessment a formal, auditable deliverable that directly supports the validation plan. The FDA expects risk management as part of a sound scientific approach to validation but is less prescriptive about the specific format of the documentation (20). The WHO presents QRM as a core principle to be applied throughout the validation lifecycle (10).

Documentation Philosophy: The Validation Master Plan (VMP)

The regulatory standing of the Validation Master Plan (VMP) is a clear point of divergence and illustrates the different philosophical approaches of the agencies.

• EMA: Annex 15 makes the VMP an explicit and mandatory requirement, detailing the minimum content that must be included to outline the entire validation program (9).
• FDA: The term "Validation Master Plan" does not appear in 21 CFR Part 211 or the 2011 Process Validation guidance. However, the regulations require written procedures for production and process controls (19). The expectation for a planned, controlled, and documented approach to validation is clear, and the VMP is the universally accepted industry method for achieving this. An absence of a VMP or equivalent planning document would be a significant concern during an FDA inspection (6, 7).
• WHO: TRS 1019 recommends the VMP as a "high-level document" that establishes the umbrella validation plan for a project or an entire site, defining responsibilities and timelines (11).

The EMA's explicit requirement for a VMP has effectively established the global best practice. A multinational company seeking to create a single, harmonized quality system will almost invariably adopt the VMP structure, as doing so satisfies the direct mandate of the EMA while also meeting the implicit expectations of the FDA and the recommendations of the WHO.

A comparative analysis of the three frameworks reveals both harmonization and divergence. In terms of core philosophy, the FDA's approach is process-centric, viewing qualification as a component of the larger Process Performance Qualification (PPQ) (1, 3). In contrast, the EMA's framework is system- and plan-centric, mandating a lifecycle-managed approach governed by a VMP (5, 9). The WHO's guidance is principles-centric, establishing qualification as a foundational prerequisite to process validation (10). A key point of divergence is the requirement for a Validation Master Plan (VMP). It is a mandatory requirement for the EMA (9), considered good practice but not mandatory by the FDA (6, 7), and recommended by the WHO (11). All three bodies encourage leveraging commissioning data, with the FDA and EMA explicitly supporting it as a path to efficiency (13, 9). The definitions of IQ, OQ, and PQ are aligned with industry standards across all three, though the EMA and WHO provide more formal definitions in their guidance (5, 9, 10). Finally, while all three have integrated Quality Risk Management, the EMA's mandate is the most explicit in Annex 15 (9), with the FDA strongly encouraging it (3, 20) and the WHO including it as a core principle (10).

Conclusion

The global regulatory landscape for pharmaceutical equipment commissioning and qualification is characterized by a strong and accelerating trend toward harmonization. The core principles of a lifecycle approach, the application of quality risk management, and the integration of commissioning and qualification activities are now central tenets of the frameworks established by the FDA, EMA, and WHO. This convergence, largely driven by the influence of ICH guidelines, allows multinational manufacturers to develop more unified and efficient global quality systems.

Despite this alignment, notable divergences persist, primarily in the level of regulatory prescriptiveness. The EMA's framework, through Annex 15, is the most detailed, with explicit mandates for a Validation Master Plan and documented risk assessments to justify the scope of validation. In contrast, the FDA's approach is more performance-based, establishing the required outcomes in its regulations while allowing manufacturers flexibility in the methodology used to achieve and document compliance, provided it is scientifically sound and risk-based. The WHO provides a comprehensive and harmonized baseline that serves as a global standard and a foundation for national regulatory bodies. For global pharmaceutical manufacturers, navigating this environment requires a quality system that is robust enough to meet the most stringent explicit requirements while remaining flexible enough to apply risk-based principles efficiently across all operations.

Bibliography

1. U.S. Food and Drug Administration. (2024). Title 21 Code of Federal Regulations Part 211: Current Good Manufacturing Practice for Finished Pharmaceuticals. Retrieved from https://www.ecfr.gov/current/title-21/chapter-I/subchapter-C/part-211 (Accessed October 23, 2025).
2. U.S. Food and Drug Administration. (2023, May). Current Good Manufacturing Practice (CGMP) Regulations. Retrieved from https://www.fda.gov/drugs/pharmaceutical-quality-resources/current-good-manufacturing-practice-cgmp-regulations (Accessed October 23, 2025).
3. U.S. Food and Drug Administration. (2011, January). Guidance for Industry: Process Validation: General Principles and Practices. Retrieved from https://www.fda.gov/files/drugs/published/Process-Validation--General-Principles-and-Practices.pdf (Accessed October 23, 2025).
4. U.S. Food and Drug Administration. (2024, May). Process Validation: A Lifecycle Approach [Presentation]. Retrieved from https://www.fda.gov/media/179081/download (Accessed October 23, 2025).
5. PSC Biotech. (2024, January 24). CQV: Where to Start? A Comprehensive Guide to Commissioning, Qualification, and Validation. Retrieved from https://biotech.com/2024/01/24/cqv-comprehensive-guide-to-commissioning-qualification-validation/ (Accessed October 23, 2025).
6. Astrix. (n.d.). Creating an Effective Validation Master Plan. Retrieved from https://astrixinc.com/blog/lab-compliance/creating-an-effective-validation-master-plan/ (Accessed October 23, 2025).
7. Egnyte. (n.d.). What Is a Validation Master Plan (VMP)?. Retrieved from https://www.egnyte.com/guides/life-sciences/validation-master-plan (Accessed October 23, 2025).
8. European Commission. (2013, February 22). EudraLex - Volume 4 - Good Manufacturing Practice (GMP) guidelines. Retrieved from http://www.it-asso.com/gxp/eudralex_v27/contents/homev4.htm (Accessed October 23, 2025).
9. European Commission. (2015, March 30). EudraLex Volume 4, EU Guidelines for Good Manufacturing Practice for Medicinal Products for Human and Veterinary Use, Annex 15: Qualification and Validation. Retrieved from https://health.ec.europa.eu/document/download/7c6c5b3c-4902-46ea-b7ab-7608682fb68d_en?filename=2015-10_annex15.pdf (Accessed October 23, 2025).
10. World Health Organization. (2019). WHO Technical Report Series, No. 1019, Annex 3: Good manufacturing practices: guidelines on validation. Retrieved from https://www.who.int/docs/default-source/medicines/norms-and-standards/guidelines/production/trs1019-annex3-gmp-validation.pdf (Accessed October 23, 2025).
11. World Health Organization. (2006). WHO Technical Report Series, No. 937, Annex 4: Supplementary guidelines on good manufacturing practices: validation. Retrieved from(https://pbe-expert.com/wp-content/uploads/2018/04/WHO_TRS937_ANNEX4_VALIDATION.pdf) (Accessed October 23, 2025).
12. ValGenesis. (2024, January 25). Commissioning and Qualification in Pharma: An Overview. Retrieved from https://www.valgenesis.com/blog/commissioning-and-qualification-in-pharma-an-overview (Accessed October 23, 2025).
13. Performance Validation. (n.d.). Commissioning and Qualification – An Overview. Retrieved from https://perfval.com/commissioning-and-qualification-an-overview/ (Accessed October 23, 2025).
14. Wrigley, G. (2011, June 2). ASTM E2500 Case Study: Transitioning from Traditional Qualification to Verification [Presentation]. Retrieved from(https://www.scribd.com/document/651396633/ASTM-E2500-Verification-approachwrigley) (Accessed October 23, 2025).
15. CAI. (n.d.). Release on ISPE Baseline Guide 5 for Commissioning and Qualification. Retrieved from https://caiready.com/life-sciences/blog/release-on-ispe-baseline-guide-5-for-commissioning-and-qualification/ (Accessed October 23, 2025).
16. International Society for Pharmaceutical Engineering. (2019, June 1). ISPE Baseline Guide: Volume 5 - Commissioning and Qualification, 2nd Edition. Retrieved from https://store.accuristech.com/standards/ispe-baseline-guide-volume-5-commissioning-and-qualification-2nd-edition?product_id=2076371 (Accessed October 23, 2025).
17. Scilife. (n.d.). 21 CFR Part 211: A Comprehensive Guide. Retrieved from https://www.scilife.io/glossary/21-cft-part-211 (Accessed October 23, 2025).
18. U.S. Food and Drug Administration. (2024). Title 21 Code of Federal Regulations Part 211, Subpart D: Equipment. Retrieved from(https://www.ecfr.gov/current/title-21/chapter-I/subchapter-C/part-211/subpart-D) (Accessed October 23, 2025).
19. U.S. Food and Drug Administration. (2015). Quality, Production, Laboratory, Materials, Facilities and Equipment, Packaging and Labeling [Presentation]. Retrieved from https://www.fda.gov/downloads/drugs/developmentapprovalprocess/smallbusinessassistance/ucm456370.pdf (Accessed October 23, 2025).
20. International Council for Harmonisation. (2000, November 10). ICH Q7 Good Manufacturing Practice for Active Pharmaceutical Ingredients. Retrieved from https://www.ema.europa.eu/en/documents/scientific-guideline/ich-q-7-good-manufacturing-practice-active-pharmaceutical-ingredients-step-5_en.pdf (Accessed October 23, 2025).
21. Scilife. (n.d.). EudraLex FAQs: Your Guide to EU Pharmaceutical Regulations. Retrieved from https://www.scilife.io/blog/eudralex-faqs (Accessed October 23, 2025).
22. CAI. (2025, September 5). Reimagining Pharmaceutical Manufacturing: Why the latest E2500-25 Standard Revision Demands Immediate Action. Retrieved from https://caiready.com/life-sciences/blog/reimagining-pharmaceutical-manufacturing-why-the-latest-e2500-25-standard-revision-demands-immediate-action/ (Accessed October 23, 2025).
23. Watler, P. (n.d.). ASTM E 2500. Retrieved from https://www.scribd.com/document/176112023/Astm-2500 (Accessed October 23, 2025).
24. PQE Group. (n.d.). ASTM E2500: a new approach to Validation. Retrieved from https://blog.pqegroup.com/commissioning-qualification/astm-e2500-qualification-approach (Accessed October 23, 2025).
25. Investigations of a Dog. (2024, May 29). The ASTM E2500 Approach to Validation. Retrieved from https://investigationsquality.com/2024/05/29/astm-e2500-approach-to-validation/ (Accessed October 23, 2025).
26. BioBoston Consulting. (n.d.). Optimize Pharmaceutical Systems with Critical Aspects Identification & Verification. Retrieved from https://biobostonconsulting.com/optimize-pharmaceutical-systems-with-critical-aspects-identification-verification/ (Accessed October 23, 2025).
27. Pharmadocx. (n.d.). Conducting Effective Design Qualification in Pharmaceutical Industry. Retrieved from https://pharmadocx.com/conducting-effective-design-qualification-in-pharmaceutical-industry/ (Accessed October 23, 2025).
28. International Society for Pharmaceutical Engineering. (2020, February). ISPE Boston Chapter Webinar: ISPE Baseline Guide Volume 5, 2nd Edition [Presentation]. Retrieved from(https://www.ispeboston.org/download/educational_presentations/2020/ISPE-Boston-February-2020-Webinar-BG5-2nd-Ed.pdf) (Accessed October 23, 2025).