Models of Verification

In the pharmaceutical industry, qualification and validation is a critical process to ensure the quality, safety, and efficacy of products. Over the years, several models have emerged to guide efforts for facilities, utilities, systems, equipment, and processes. This blog post will explore three prominent models: the 4Q model, the V-model, and the W-model. We’ll also discuss relevant regulatory guidelines and industry standards.

The 4Q Model

The 4Q model is a widely accepted approach to qualification in the pharmaceutical industry. It consists of four stages:

Design Qualification (DQ): This initial stage focuses on documenting that the design of facilities, systems, and equipment is suitable for the intended purpose. DQ should verify that the proposed design of facilities, systems, and equipment is suitable for the intended purpose. The requirements of the user requirements specification (URS) should be verified during DQ.
Installation Qualification (IQ): IQ verifies that the equipment or system has been properly installed according to specifications. IQ should include verification of the correct installation of components and instrumentation against engineering drawings and specifications — the pre-defined criteria.
Operational Qualification (OQ): This stage demonstrates that the equipment or system operates as intended across the expected operating ranges. OQ should ensure the system is operating as designed, confirming the upper and lower operating limits, and/or “worst case” conditions. Depending on the complexity of the equipment, OQ may be performed as a combined Installation/Operation Qualification (IOQ). The completion of a successful OQ should allow for the finalization of standard operating and cleaning procedures, operator training, and preventative maintenance requirements.
Performance Qualification (PQ): PQ confirms that the equipment or system consistently performs as expected under routine production conditions. PQ should normally follow the successful completion of IQ and OQ, though in some cases, it may be appropriate to perform PQ in conjunction with OQ or Process Validation. PQ should include tests using production materials, qualified substitutes, or simulated products proven to have equivalent behavior under normal operating conditions with worst-case batch sizes. The extent of PQ tests depends on the results from development and the frequency of sampling during PQ should be justified.

The V-Model

The V-model, introduced by the International Society of Pharmaceutical Engineers (ISPE) in 1994, provides a visual representation of the qualification process:

The left arm of the “V” represents the planning and specification phases.
The bottom of the “V” represents the build and unit testing phases.
The right arm represents the execution and qualification phases.

This model emphasizes the relationship between each development stage and its corresponding testing phase, promoting a systematic approach to validation.

The W-Model

The W-model is an extension of the V-model that explicitly incorporates commissioning activities:

The first “V” represents the traditional V-model stages.
The center portion of the “W” represents commissioning activities.
The second “V” represents qualification activities.

This model provides more granularity to what is identified as “verification testing,” including both commissioning (e.g., FAT, SAT) and qualification testing (IQ, OQ, PQ).

Aspect	4Q Model	V-Model	W-Model
Stages	DQ, IQ, OQ, PQ	User Requirements, Functional Specs, Design Specs, IQ, OQ, PQ	User Requirements, Functional Specs, Design Specs, Commissioning, IQ, OQ, PQ
Focus	Sequential qualification stages	Linking development and testing phases	Integrating commissioning with qualification
Flexibility	Moderate	High	High
Emphasis on Commissioning	Limited	Limited	Explicit
Risk-based Approach	Can be incorporated	Can be incorporated	Inherently risk-based

Where Qualifcation Fits into the Regulatory Landscape and Industry Guidelines

WHO Guidelines

The World Health Organization (WHO) provides guidance on validation and qualification in its “WHO good manufacturing practices for pharmaceutical products: main principles”. While not explicitly endorsing a specific model, WHO emphasizes the importance of a systematic approach to validation.

EMA Guidelines

The European Medicines Agency (EMA) has published guidelines on process validation for the manufacture of biotechnology-derived active substances and data to be provided in regulatory submissions. These guidelines align with the principles of ICH Q8, Q9, and Q10, promoting a lifecycle approach to validation.

Annex 15 provides guidance on qualification and validation in pharmaceutical manufacturing. Regarding Design Qualification (DQ), Installation Qualification (IQ), Operational Qualification (OQ), and Performance Qualification (PQ) which is pretty much either the V or W model.

Annex 15 emphasizes a lifecycle approach to validation, considering all stages from initial development of the user requirements specification through to the end of use of the equipment, facility, utility, or system. The main stages of qualification and some suggested criteria are indicated as a “could” option, allowing for flexibility in approach.

Annex 15 provides a structured yet flexible approach to qualification, allowing pharmaceutical manufacturers to adapt their validation strategies to the complexity of their equipment and processes while maintaining compliance with regulatory requirements.

FDA Guidance

The U.S. Food and Drug Administration (FDA) issued its “Guidance for Industry: Process Validation: General Principles and Practices” in 2011. This guidance emphasizes a lifecycle approach to process validation, consisting of three stages: process design, process qualification, and continued process verification.

ASTM E2500

ASTM E2500, “Standard Guide for Specification, Design, and Verification of Pharmaceutical and Biopharmaceutical Manufacturing Systems and Equipment,” provides a risk-based approach to validation. It introduces the concept of “verification” as an alternative to traditional qualification steps, allowing for more flexible and efficient validation processes.

ISPE Guidelines

The International Society for Pharmaceutical Engineering (ISPE) has published several baseline guides and good practice guides that complement regulatory requirements. These include guides on commissioning and qualification, as well as on the implementation of ASTM E2500.

Baseline Guide Vol 5: Commissioning & Qualification (Second Edition)

This guide offers practical guidance on implementing a science and risk-based approach to commissioning and qualification (C&Q). Key aspects include:

Applying Quality Risk Management to C&Q
Best practices for User Requirements Specification, Design Review, Design Qualification, and acceptance/release
Efficient use of change management to support C&Q
Good Engineering Practice documentation standards

The guide aims to simplify and improve the C&Q process by integrating concepts from regulatory guidances (EMA, FDA, ISO) and replacing certain aspects of previous approaches with Quality Risk Management and Good Engineering Practice concepts.

Conclusion

While the 4Q, V, and W models provide structured approaches to validation, the pharmaceutical industry is increasingly moving towards risk-based and science-driven methodologies. Regulatory agencies and industry organizations are promoting flexible approaches that focus on critical aspects of product quality and patient safety.

By leveraging guidelines such as ASTM E2500 and ISPE recommendations, pharmaceutical companies can develop efficient validation strategies that meet regulatory requirements while optimizing resources. The key is to understand the principles behind these models and guidelines and apply them in a way that best suits the specific needs of each facility, system, or process.

The Types of User Requirements

User requirements are typically divided into several categories to ensure comprehensive coverage of all aspects of product development, manufacturing, and quality control and to help guide the risk-based approach to verification.

Product User Requirements

These requirements relate directly to the product being manufactured and the processes involved in its production. They include:

Critical Quality Attributes (CQAs) of the product
Critical Process Parameters (CPPs)
Required throughput and production conditions
Specifications for raw materials and finished products

Building the FUSE(P) User Requirements in an ICH Q8, Q9 and Q10 World

Quality Requirements

Quality requirements focus on ensuring that the product meets all necessary quality standards and regulatory compliance. This category includes:

Good Manufacturing Practices (GMP) compliance, including around cleaning, cross-contamination, etc to ensure compliance with various regulations such as FDA guidelines, EU GMP, and ICH standards.
Documentation and record-keeping standards
Contamination control strategies are a key part of quality requirements, as they are essential for maintaining product quality and patient safety.
Data integrity requirements fall under this category, as they are crucial for ensuring the quality and reliability of data.

Not everyone advocates for this breakdown but I am a huge proponent as it divides the product specific requirements for the more standard must’s of meeting the cGMPs that are not product specific. This really helps when you are a multi-product facility and it helps define what is in the PQ versus what is in the PPQ.

Safety User Requirements

Safety requirements address the safety of personnel, patients, and the environment. They encompass:

Occupational health and safety measures
Environmental protection protocols
Patient safety considerations in product design

General User Requirements

General requirements cover broader aspects of the manufacturing system and facility. These may include:

Facility design and layout
Equipment specifications
Utility requirements (e.g., power, water, HVAC)
Maintenance procedures

By categorizing user requirements in this way, pharmaceutical companies can ensure a comprehensive approach to product development and manufacturing, addressing all critical aspects from product quality to regulatory compliance and safety. This will help drive appropriate verification.

Crafting Good User Requirements

Water, Water, Everywhere

Everyone probably feels like the above illustration sooner or later about their water system.

The Critical Role of Water in Pharmaceutical Manufacturing

In the pharmaceutical industry, we often joke that we’re primarily water companies that happen to make drugs on the side. This quip underscores a fundamental truth: water is a crucial component in drug manufacturing processes. Its purity and quality are paramount to ensuring the safety and efficacy of pharmaceutical products.

Why Water Quality Matters

Water is ubiquitous in pharmaceutical manufacturing, used in everything from cleaning equipment to serving as a key ingredient in many formulations. Given its importance, regulatory bodies like the FDA and EMA have established stringent Good Manufacturing Practice (GMP) guidelines for water systems in pharmaceutical facilities.

GMP Requirements for Water Systems

The GMPs mandate that water systems be meticulously designed, constructed, installed, commissioned, qualified, monitored, and maintained. The primary goal? Preventing microbiological contamination. This comprehensive approach encompasses several key areas:

System Design: Water systems must be engineered to minimize the risk of contamination.
Construction and Installation: Materials and methods used must meet high standards to ensure system integrity.
Commissioning and Qualification: Rigorous testing is required to verify that the system performs as intended.
Monitoring: Ongoing surveillance is necessary to detect any deviations from established parameters.
Maintenance: Regular upkeep is crucial to maintain system performance and prevent degradation.

Key Regulatory Requirements

Agency	Title	Year	URL
EMA	Guideline on the quality of water for pharmaceutical use	2020	https://www.ema.europa.eu/en/documents/scientific-guideline/guideline-quality-water-pharmaceutical-use_en.pdf
WHO	Good manufacturing practices: water for pharmaceutical use	2012	https://www.who.int/docs/default-source/medicines/norms-and-standards/guidelines/production/trs970-annex2-gmp-wate-pharmaceutical-use.pdf
US FDA	Guide to inspections of high purity water systems	2016	https://www.fda.gov/media/75927/download
PIC/S	Inspection of utilities	2014	https://picscheme.org/docview/1941
US FDA	Water for pharmaceutical use	2014	https://www.fda.gov/media/88905/download
USP	<1231> Water for pharmaceutical purposes	2020	Not publicly available
USP	<543> Water Conductivity	2020	Not publicly available
USP	<85> Bacterial Endotoxins Test	2020	Not publicly available
USP	<643> Total Organic Carbon	2020	Not publicly available
Ph. Eur.	Monograph 0168 (Water for injections)	2020	Not publicly available
Ph. Eur.	Monograph 0008 (Purified water)	2020	Not publicly available

Specific Measures for Contamination Prevention

To meet these GMP requirements, pharmaceutical manufacturers must implement several specific measures:

Minimizing Particulates

Particulate matter in water can compromise product quality and potentially harm patients. Filtration systems and regular cleaning protocols are essential to keep particulate levels in check.

Controlling Microbial Contamination

Microorganisms can proliferate rapidly in water systems if left unchecked. Strategies to prevent this include:

Regular sanitization procedures
Maintaining appropriate water temperatures
Implementing effective water treatment technologies (e.g., UV light, ozonation)

Preventing Endotoxin Formation

Endotoxins, produced by certain bacteria, can be particularly problematic in pharmaceutical water systems. Measures to prevent endotoxin formation include:

Minimizing areas where water can stagnate
Ensuring complete drainage of pipes
Regular system flushing

The Ongoing Challenge

Maintaining water quality in pharmaceutical manufacturing is not a one-time effort but an ongoing process. It requires constant vigilance, regular testing, and a commitment to continuous improvement. As regulations evolve and our understanding of potential contaminants grows, so too must our approaches to water system management.

Types of Water

These water types are defined and regulated by pharmacopeias such as the United States Pharmacopeia (USP), European Pharmacopoeia (Ph. Eur.), and other regional standards. Pharmaceutical manufacturers must adhere to the specific requirements outlined in these references to ensure water quality and safety in drug production.

Potable Water

Potable water, also known as drinking water, may be used for some pharmaceuticals bt is more commonly used in cosmetics. It can also be used for cleanings walls and floors in non-asceptic areas.

Key points:

Must comply with EPA standards or comparable regulations in the EU/Japan
Can be used to manufacture drug substances (bulk drugs)
Not suitable for preparing USP dosage forms or laboratory reagents

Purified Water (PW)

Purified water is widely used in pharmaceutical manufacturing for non-sterile preparations.

Specifications (USP <1231>):

Conductivity: ≤1.3 μS/cm at 25°C
Total organic carbon (TOC): ≤500 ppb
Microbial limits: ≤100 CFU/mL

Applications:

Non-parenteral preparations
Cleaning equipment for non-parenteral products
Preparation of some bulk chemicals

Water for Injection (WFI)

Water for Injection is used for parenteral drug products and has stricter quality standards.

Specifications (USP <1231>):

Conductivity: ≤1.3 μS/cm at 25°C
TOC: ≤500 ppb
Bacterial endotoxins: <0.25 EU/mL
Microbial limits: ≤10 CFU/100 mL

Production methods:

Distillation
Reverse osmosis (allowed by Ph. Eur. since 2017)

Sterile Water for Injection (SWFI)

SWFI is WFI that has been sterilized for direct administration.

Characteristics:

Sterile
Non-pyrogenic
Packaged in single-dose containers

Highly Purified Water (HPW)

Previously included in the European Pharmacopoeia, but now discontinued.

Type of Water	Description	USP Reference	EP Reference
Potable Water	Meets drinking water standards, used for early stages of manufacturing	Not applicable	Not applicable
Purified Water (PW)	Used for non-sterile preparations, cleaning equipment	USP <1231>	Ph. Eur. 0008
Water for Injection (WFI)	Used for parenteral products, higher purity than PW	USP <1231>	Ph. Eur. 0169
Sterile Water for Injection (SWFI)	WFI that has been sterilized for direct administration	USP <1231>	Ph. Eur. 0169
Bacteriostatic Water for Injection	Contains bacteriostatic agents, for multiple-dose use	USP <1231>	Ph. Eur. 0169
Sterile Water for Irrigation	Packaged in single-dose containers larger than 1L	USP <1231>	Ph. Eur. 1116
Sterile Water for Inhalation	For use in inhalators, less stringent endotoxin levels	USP <1231>	Ph. Eur. 1116
Water for Hemodialysis	Specially treated for use in hemodialysis, produced on-site	USP <1231>	Not specified

Additional relevant USP chapters:

USP <645>: Water for Pharmaceutical Purposes – Microbial Attributes
USP <85>: Bacterial Endotoxins Test

Always refer to the most current versions of the pharmacopoeial monographs and regulatory guidelines for detailed information.

Good Water System Design

Hygienic and Sanitary Design

The cornerstone of any good water system is its hygienic and sanitary design. This principle encompasses several aspects:

Smooth, cleanable surfaces: All surfaces in contact with water should be smooth, non-porous, and easily cleanable to prevent biofilm formation.
Self-draining components: Pipes and tanks should be designed to drain completely, eliminating standing water that could harbor microorganisms.
Accessibility: All parts of the system should be easily accessible for inspection, cleaning, and maintenance.

Material Selection

Choosing the right materials is crucial for maintaining water quality and system integrity:

Corrosion resistance: Use materials that resist corrosion, such as stainless steel (316L grade for high-purity applications) or appropriate food-grade plastics.
Smooth internal finish: Crevices are places where corrosion happens, electropolishing improves the resistance of stainless steel to corrosion.
Leachate prevention: Select materials that do not leach harmful substances into the water, even under prolonged contact or elevated temperatures.
Non-adsorptive surfaces: Avoid materials that may adsorb contaminants, which could later be released back into the water.

Microbial Control

Preventing microbial growth is essential for water system safety:

Elimination of dead legs: Design piping to avoid areas where water can stagnate and microorganisms can proliferate.
Temperature control: Maintain temperatures outside the optimal range for microbial growth (typically below 20°C or above 50°C).
Regular sanitization: Incorporate features that allow for effective and frequent sanitization of the entire system.

System Integrity

Ensuring the system remains sealed and leak-free is critical:

Proper sealing: Use appropriate gaskets and seals compatible with the system’s operating conditions.
Pressure testing: Implement regular pressure tests to identify and address potential leaks promptly.
Quality connections: Utilize sanitary fittings and connections designed for hygienic applications.

Cleaning and Sanitization Compatibility

The system must withstand regular cleaning and sanitization:

Chemical resistance: Choose materials and components that can tolerate cleaning and sanitizing agents without degradation.
Thermal stability: Ensure all parts can withstand thermal sanitization processes if applicable.
CIP/SIP design: Incorporate Clean-in-Place (CIP) or Steam-in-Place (SIP) features for efficient and thorough cleaning.

Capacity and Performance

Meeting output requirements while maintaining quality is crucial:

Proper sizing: Design the system to meet peak demand without compromising water quality or flow rates.
Redundancy: Consider incorporating redundant components for critical parts to ensure continuous operation.
Efficiency: Optimize the system layout to minimize pressure drops and energy consumption.

Monitoring and Control

Implement robust monitoring systems to ensure water quality:

Sampling points: Strategically place sampling ports throughout the system for regular quality checks.
Instrumentation: Install appropriate instruments to monitor critical parameters such as flow rate, pressure, temperature, and conductivity.
Control systems: Implement automated control systems to maintain consistent water quality and system performance.

Regulatory Compliance

Ensure the system design meets all relevant regulatory requirements:

Material compliance: Use only materials approved for contact with water in your specific application.
Documentation: Maintain detailed documentation of system design, materials, and operating procedures.
Validation: Conduct thorough system qualification to demonstrate consistent performance and quality.

By adhering to these principles, you can design a water system that not only meets your capacity requirements but also ensures the highest standards of safety and quality. Remember, good water system design is an ongoing process that requires regular review and updates to maintain its effectiveness over time.

The Validation Discrepancy

I don’t like the term validation deviation, preferring to use discrepancy to cover the errors or failures that occur during qualification/validation, such as when the actual results of a test step in a protocol do not match the expected results. These discrepancies can arise for various reasons, including errors in the protocol, execution issues, or external factors.

I don’t like using the term deviation as I try to avoid terms becoming too overused in too many ways. By choosing discrepancy it serves to move them to a lower order of problem so they can be addressed holistically.

Validation discrepancies really get to the heart of deciding whether the given system/process is fit-for-purpose and fit-for-use. As such, they require being addressed in a timely and pragmatic way.

And, like anything else, having an effective procedure to manage is critical.

Validation discrepancies are a great example of building problem-solving into a process.

ASTM E2500 Approach to Validation

ASTM E2500, the Standard Guide for Specification, Design, and Verification of Pharmaceutical and Biopharmaceutical Manufacturing Systems and Equipment, is intended to “satisfy international regulatory expectations in ensuring that manufacturing systems and equipment are fit for the intended use and to satisfy requirements for design, installation, operation, and performance.”

The ASTM E2500 approach is a comprehensive framework for specification setting, design, and verification of pharmaceutical and biopharmaceutical manufacturing systems and equipment. It emphasizes a risk- and science-based methodology to ensure that systems are fit for their intended use, ultimately aiming to enhance product quality and patient safety.

Despite its 17-year history, it is fair to say it is not the best-implemented standard. There are still many unrealized opportunities and some major challenges. I don’t think a single organization I’ve been in has fully aligned, and ASTM E2500 can feel aspirational.

Key Principles

Risk Management: The approach integrates risk management principles from ICH Q8, Q9, and Q10, focusing on identifying and mitigating risks to product quality and patient safety throughout the lifecycle of the manufacturing system.
Good Engineering Practices (GEP): It incorporates GEP to ensure systems are correctly designed, installed, and operated.
Flexibility and Efficiency: It strives for a more flexible and efficient organization of verification activities that can be adapted to each project’s specific context.

Know your Process

Regulatory agencies expect drugmakers to persuade them that we know our processes and that our facilities, equipment, systems, utilities, and procedures have been established based on concrete data and a thorough risk assessment. The ASTM E2500 standard provides a means of demonstrating that all of these factors have been validated in consideration of carefully evaluated risks.

What the Standard Calls for

Four Main Steps

Requirements: Define the system’s needs and critical aspects. Subject Matter Experts (SMEs) play a crucial role in this phase by defining needs, identifying critical aspects, and developing the verification strategy.
Specification & Design: Develop detailed specifications and design the system to meet the requirements. This step involves thorough design reviews and risk assessments to ensure the system functions as intended.
Verification: Conduct verification activities to confirm that the system meets all specified requirements. This step replaces the traditional FAT/SAT/IQ/OQ/PQ sequence with a more streamlined verification process that can be tailored to the project’s needs.
Acceptance & Release: Finalize the verification process and release the system for operational use. This step includes the final review and approval of all verification activities and documentation.

Four Cross-Functional Processes

Good Engineering Practices (GEP): Ensure all engineering activities adhere to industry standards and best practices.
Quality Risk Management: Continuously assess and manage risks to product quality and patient safety throughout the project.
Design Review: Regularly reviews the system design to ensure it meets all requirements and addresses identified risks.
Change Management: Implement a structured process for managing system changes to ensure that all modifications are appropriately evaluated and documented.

Applications and Benefits

Applicability: The ASTM E2500 approach can be applied to new and existing manufacturing systems, including laboratory, information, and medical device manufacturing systems.
Lifecycle Coverage: It applies throughout the manufacturing system’s lifecycle, from concept to retirement.
Regulatory Compliance: The approach is designed to conform with FDA, EU, and other international regulations, ensuring that systems are qualified and meet all regulatory expectations.
Efficiency and Cost Management: By focusing on critical aspects and leveraging risk management tools, the ASTM E2500 approach can streamline project execution, reduce time to market, and optimize resource utilization.

The ASTM E2500 approach provides a structured, risk-based framework for specifying, designing, and verifying pharmaceutical and biopharmaceutical manufacturing systems. It emphasizes flexibility, efficiency, and regulatory compliance, making it a valuable tool for ensuring product quality and patient safety.

What Makes it Different?

	ASTM E2500	The more traditional approach
Testing Approach	It emphasizes a risk-based approach, focusing on identifying and managing risks to product quality and patient safety throughout the manufacturing system’s lifecycle. This approach allows for flexibility in organizing verification activities based on the specific context and critical aspects of the system.	Typically follows a prescriptive sequence of tests (FAT, SAT, IQ, OQ, PQ) as outlined in guidelines like EU GMP Annex 15. This method is more rigid and less adaptable to the specific needs and risks of each project.
Verification vs Qualification	The term “verification” encompasses all testing activities, which can be organized more freely and rationally to optimize efficiency. Verification activities are tailored to the project’s needs and focus on critical aspects.	Follows a structured qualification process (Installation Qualification, Operational Qualification, Performance Qualification) with predefined steps and documentation requirements.
Role of Subject Matter Experts	SMEs play a crucial role from the start of the project, contributing to the definition of needs, identification of critical aspects, system design review, and development of the verification strategy. They are involved throughout the project lifecycle.	SMEs are typically involved at specific points in the project lifecycle, primarily during the qualification phases, and may not have as continuous a role as in the ASTM E2500 approach.
Integration of Good Engineering Practices	Offers greater flexibility in organizing verification activities, allowing for a more efficient and streamlined process. This can lead to reduced time to market and optimized resource utilization.	While GEP is also important, the focus is more on the qualification steps rather than integrating GEP throughout the entire project lifecycle.
Change Management	It emphasizes early and continuous change management, starting from the supplier’s site, to avoid test duplication and ensure that changes are properly evaluated and documented.	It emphasizes early and continuous change management, starting from the supplier’s site, to avoid test duplication and ensure that changes are properly evaluated and documented.
Documentation	Documentation is focused on risk management and verification activities, ensuring compliance with international regulations (FDA, EU, ICH Q8, Q9, Q10). The approach is designed to meet regulatory expectations while allowing for flexibility in documentation.	quires extensive documentation for each qualification step, which can be more cumbersome and less adaptable to specific project needs.

Opinion

I’m watching to see what the upcoming update to Annex 15 will do to address the difficulties some see between an ATSM E2500 approach and the European regulations. I also hope we will see an update to ISPE Baseline® Guide Volume 5: Commissioning and Qualification to align an approach.

ISPE Baseline® Guide Volume 5	ATSM E2500
Design inputs Impact assessment Design Qualification Commissioning Multiple trial runs to get things right IQ, OQ, PQ, and acceptance criteria GEP Scope and QA Scope overlapped Focused on Documentation Deliverables Change Management	Design inputs Design Review Risk Mitigation Critical Control Parameters define Acceptance Criteria Verification Testing Performance Testing GEP Scope and QA Scope have a clear boundary Process, Product Quality and Patient Safety Quality by Design, Design Space, and Continuous Improvement

To be honest I don’t think ATSM E2500, ISPE Guide 5, or anything else has the balance just right. And your program ends up being a triangulation between these and the regulations. And don’t even bring in trying to align GAMP5 or USP <1058> or…or…or…

And yes, I do consider this part of my 3-year plan. I look forward to the challenges of a culture shift, increased SME involvement, formalization of GEPs (and teaching engineers how to write), effective change management, timely risk assessments, and comprehensive implementation planning.