URS: A Critical Tool to Pharma Manufacturing Excellence

The following is a summary of a GxP Expert Series webinar featuring the viewpoints and opinions of Marisa Remsing, GxP validation/qualification engineer, ELPRO Messtechnik GmbH; Dirk Raubald, manufacturing engineering at Johnson & Johnson’s Innovative Medicine Advanced Therapies Supply Chain EMEA; and Steph Punter, GxP validation/qualification engineer with ELPRO Services, Inc.

In the highly regulated world of pharmaceutical and life sciences manufacturing, the user requirement specification (URS) stands as a critical cornerstone of quality, compliance, and operational excellence.

At its core, a URS is a strategic blueprint that articulates the precise capabilities, limitations, and critical requirements of a system. Its use has evolved dramatically over the years from a basic collection of testable requirements to a comprehensive framework that serves multiple critical purposes. It now functions as a multifaceted tool for regulatory compliance, vendor accountability, and a consistent reference point throughout a project's entire lifecycle.

The regulatory landscape surrounding URS is complex and multilayered. Global regulatory bodies offer various perspectives that reflect the critical nature of pharmaceutical system design. The European Union's Eudralex guidelines emphasize the importance of defining equipment specifications and maintaining a consistent reference throughout the validation lifecycle. The International Society for Pharmaceutical Engineering (ISPE) focuses on verification through rigorous testing, stressing the importance of traceable qualification documentation while simultaneously underlining the importance of designer freedom in meeting requirements.

The U.S. Food and Drug Administration (FDA) takes a slightly different approach, mandating that equipment design must be appropriate for its intended use, with clear documentation of requirements. Meanwhile, China's NMPA regulations emphasize the alignment of location, design, and production requirements, focusing intensely on verifying premises and equipment installation. The World Health Organization (WHO) goes a step further, advocating for comprehensive qualification that extends beyond paper-based and installation verifications, recommending operational and performance qualifications that reflect routine operating conditions.

Always keep in mind that a URS is a living document… that lives with your system. When your system is changed… the URS also changes.

Marisa Remsing, ELPRO

To navigate this complex regulatory environment, the webinar presenters outlined a structured four-step methodology for URS development that has proven effective across multiple pharmaceutical and life sciences organizations:

1. Clarifying the “Who”

This first step involves assembling a comprehensive team of subject matter experts (SMEs). This is not simply about gathering technical personnel, but creating a diverse group that ideally includes quality managers, operations and engineering personnel, maintenance teams, standard operating procedure (SOP) creators, end-users and key stakeholders.

Establishing a formal approval process is critical, ensuring that multiple perspectives are considered and that the final document represents a holistic view of system requirements.

2. Inputs to URS Development

This stage begins with a comprehensive understanding of the following aspects and requires deep technical insight and a holistic view of the entire system's operational context.

• Regulatory filing

• Product storage requirements

• Stability considerations

• Critical quality attributes

• Critical process parameters

• Critical parameters

• Non-GMP/GDP and site/company requirements

Developing the URS Document

The format and framework of the document itself should follow a carefully structured approach:

• Separated chapters for different trades

• A comprehensive traceability matrix

• Which can be a separate document

• Clear prioritization of requirements

• Application of the SMART principle (Specific, Measurable, Achievable, Realistic, Testable)

Outputs from URS

The final document is a key deliverable that serves for all of the following:

• Detailed design specifications

• Bill of Materials (BOM)

• A foundational framework for vendor selection

• Comprehensive risk assessment basis

• A clear verification and testing framework

When defining critical parameters, always give them testable values…don’t define requirements you can't test.

Marisa Remsing, ELPRO

The presenters were candid about the common pitfalls that can derail URS development. These include generalized statements, attempts to define specific design details, using ambiguous or untestable parameters, combining multiple requirements, duplicating requirements, late-stage preparation, and poor vendor communication.

To counter these challenges, they recommended:

• Specifying precise guideline references

• Leaving design fulfillment to specialized professionals

• Using SMART parameter values (see above)

• Addressing one requirement at a time

• Conducting thorough SME reviews

• Involving stakeholders early in the process

• Creating a living document that can adapt to changing requirements

• Leveraging the URS as a powerful tool for vendor communication

Dirk shared Johnson & Johnson’s approach, which provides an exemplary model of URS implementation. Their comprehensive framework includes:

• A global quality management system

• Specific policies for facilities, utilities, and equipment

• Standardized procedures for commissioning and qualification

• Tailored approaches for different equipment types

• An integrated risk assessment methodology

Dirk explained that robust URS should encompass four key elements:

1. Context and General Information

• Clear purpose and scope

• Defined roles and responsibilities

• Essential definitions

2. System Overview

• High-level process description

• Clear system boundaries

• Interface specifications

3. Detailed Requirements

• Classified and traceable specifications

• Mission-critical functional requirements

4. Supporting Documentation

• Comprehensive references

• Company procedures

• Technical information and contextual details

The ultimate takeaway was profound yet simple: a well-developed URS transcends mere documentation. It is a strategic tool that bridges user needs, regulatory requirements, and technological implementation.

A comprehensive, focused URS can drive project efficiency and accelerate time to market for critical medications and therapies.

Dirk Raubald, Johnson & Johnson

Dirk emphasized focusing on clarity, traceability, and comprehensive stakeholder involvement. In doing so, he says organizations can create URS that not only ensure compliance but also drive project, start-up and operational efficiency and ultimately accelerate the safe and effective delivery of critical medical solutions.

In an industry where precision can mean the difference between life and death, the user requirement specification emerges as more than a procedural requirement—it is a critical pathway to pharmaceutical excellence, ensuring that complex systems meet the highest standards of quality, safety, and performance.

The following questions were posed during the session and answered by the panelists:

Q. Could you please share some examples of URS for walk-in cooler units?

A: Dirk just mentioned one of the ISPE guidelines, which you can actually purchase from their website, and maybe we can share a link or something to that in the chat. Their controlled temperature chambers guideline actually has a full example in the appendix and it is actually specifically for a 2-8 °C walk-in cold room so that would be a good starter point. However, of course you can reach out to us for any support that you need as well.

Q: What happens if the system is already purchased and up and running? Can you somehow cover the URS and qualification part retrospectively?

A: Technically, for some time, the GMP guidance documents no longer support retrospective qualification. Hence, you should check back with your quality system and see what the processes say about how to deal with such cases. For instance, one could raise a deviation or likewise vehicle to demonstrate and identify a gap. Thus, you can follow your processes and stay in control. Usually, these processes will let you analyze, why there was no URS, qualification, etc. Next you determine the impact – which is particularly important if you used that very system as part of your manufacturing operations. Then you will define and agree on activities, timelines and responsibilities to remediate the gap and measures to prevent them from recurring. Here one activity can be to write a URS for that system, as it stands currently, and qualify it against it. Ultimately, you will have also checkpoints defined in your deviation to stay in control of the entire remediation process and determine the effectiveness at the end.

NOTE: The content of this webinar summary is for informational purposes only and does not constitute professional advice. The views expressed herein are those of the presenters and do not necessarily reflect the views of Johnson & Johnson. While every effort has been made to ensure the accuracy of the information provided, Johnson & Johnson makes no warranties or representations regarding the completeness or suitability of the information for any purpose. Attendees should seek professional advice tailored to their individual circumstances.