Software Validation: A Guide for Life Sciences Professionals

In life sciences, software underpins nearly every operation — from managing laboratories and manufacturing lines to running embedded code for Software as a Medical Device (SaMD). The accuracy and reliability of these systems are critical, not only for meeting regulatory demands but also for ensuring patient safety, maintaining data integrity, and safeguarding product quality. Health authorities worldwide, including the FDA (U.S. Food and Drug Administration) and EMA (European Medicines Agency), require that software used in the life sciences industry be proven fit for its intended use. This is where validation comes in. Today, however, validation is evolving: modern approaches, guided by GAMP 5 principles and FDA’s Computer Software Assurance (CSA) framework, emphasize risk-based assurance, critical thinking, lifecycle monitoring, and vendor oversight. The sections ahead outline how to apply these principles across the validation lifecycle — from planning and requirements, to testing, release, and ongoing monitoring — so that validation becomes not just a compliance exercise, but a business enabler that strengthens quality culture and prepares you for the future of SaaS (Software as a Service), cloud, and Artificial Intelligence (AI)-enabled systems. 

Defining Software Validation 

According to the FDA’s General Principles of Software Validation (21 CFR Part 820, Subpart C), software validation is: 

"Confirmation by examination and provision of objective evidence that software specifications conform to user needs and intended uses, and that the requirements implemented through software can be consistently fulfilled." 

In essence, software validation is the process of showing—through structured testing and documented evidence—that a system fulfills its requirements and supports its intended purpose. Put simply: does the software reliably do what it was designed to do, every time, without compromising product quality, patient safety or data integrity? 

Regulatory Framework & Guidance Documents 

When it comes to validating medical devices for the North American and the European markets, there are key references to consider: 

• FDA 21 CFR Part 11:  This regulation by the FDA governs the use of electronic records and electronic signatures in place of paper records and handwritten signatures in regulated industries. The goal is to ensure that electronic records and signatures are trustworthy, reliable, and equivalent to paper records and handwritten signatures, thus enabling the paperless management of compliance data while maintaining integrity, security, and traceability. 

• FDA 21 CFR Part 820: A regulation that sets the FDA requirements for quality management systems (QMS) specific to manufacturers of medical devices marketed in the U.S. The goal is to ensure medical devices are designed, produced, and distributed in a way that guarantees their safety, effectiveness, and compliance through rigorous design controls, production processes, complaint handling, CAPA (Corrective and Preventive Actions), and record-keeping systems.   

Note: Originally known as the Quality System Regulation (QSR), it was officially revised and renamed to Quality Management System Regulation (QMSR) in 2024.  This was done to better align with the ISO 13485:2016 standard below.  The new version is becoming enforceable on February 2, 2026.    

• GAMP 5: Good Automated Manufacturing Practice (GAMP) 5 is a guideline developed by the ISPE (International Society for Pharmaceutical Engineering) providing a risk-based approach to validating computerized systems in regulated industries (especially pharmaceuticals and biotech). The goal is to promote a scalable, pragmatic approach to computerized systems validation that ensures quality and regulatory compliance while minimizing unnecessary effort. GAMP 5 emphasizes system lifecycle management and risk-based testing. 

• FDA Computer Software Assurance (CSA, 2022 draft guidance): An FDA initiative that modernizes the traditional CSV approach. CSA emphasizes critical thinking, risk-based decision-making, and assurance through appropriate testing methods (scripted, unscripted, exploratory). Its goal is to shift focus away from excessive documentation toward proportionate, value-driven validation activities that assure patient safety, product quality, and data integrity. 

• ISO 13485: It’s an international standard that outlines the requirements for a QMS specific to the medical device industry. It harmonizes global regulatory requirements. The goal is to ensure organizations can demonstrate the ability to provide medical devices and related services that consistently meet customer and regulatory requirements, covering design, production, installation, and servicing of medical devices. 

• EU MDR 2017/745: A regulation issued by the European Union (EU) to replace the previous Medical Device Directive (MDD). It introduces stricter requirements for the approval and post-market surveillance of medical devices in the EU. The goal is to enhance the safety and performance of medical devices in the EU market by imposing more rigorous clinical evaluation, transparency, traceability, and post-market monitoring requirements. 

• Annex 11 of EU GMP: Part of the EudraLex – Volume 4 - Good Manufacturing Practice (GMP) guidelines, Annex 11 provides principles for the use of computerized systems in GMP-regulated activities. The goal is to ensure that computerized systems used in manufacturing and quality control processes are validated, reliable, secure, and capable of ensuring data integrity and product quality, aligning with GMP requirements. 

  
  

Across these frameworks, one principle remains central: validation activities must be proportional to the risks the software poses to patients' safety and product quality. 

Which Systems Require Validation? 

Examples of software use in the medical device industry subject to validation include but are not limited to: 

• Software as a Medical Device (SaMD) 

• Embedded software in medical devices (e.g., firmware) 

• Quality Management Systems (QMS) 

• Clinical Trial Management Systems (CTMS) 

• Electronic Document Management Systems (EDMS) 

• Laboratory Information Management Systems (LIMS) 

• Manufacturing Execution Systems (MES) 

It is important to remember that even commercially available off-the-shelf software (COTS) must be validated when used in a GxP-regulated context. GxP being "Good Practices", a term used in the life sciences industry to refer to applicable regulations and guidelines with the "x" representing the specific field (example: Manufacturing, Clinical, Laboratory etc..).

The Validation Lifecycle: Best Practices 

1. Validation Planning  

The Validation Master Plan (VMP), or the Validation Plan (VLP) depending on the system size and complexity, is produced during the Validation Planning phase and acts as a roadmap for the validation effort. It defines scope, responsibilities, timelines, risk classifications, and references to applicable standards and SOPs. In more details the VMP defines: 

• Scope of the validation effort, often in the form of an overview of the system that will be undergoing validation; 

• Roles and responsibilities of the validation team across quality, IT, and business units. Such roles should minimally include a Process Owner, a System Owner and a Quality Assurance representative; 

• System Risk Assessment (SRA) to classify the system as a whole (High/Medium/Low risk) based on intended use, data criticality, and regulatory impact; 

• Validation strategy and timelines tailored to the software’s GxP impact, the quality level of the software provider and system risk determined within the SRA;  

• References to applicable SOPs, lifecycle models (e.g., V-model, Agile), and regulatory frameworks such as FDA 21 CFR Part 11 and EU Annex 11 that are relevant to the system being validated. 

  
  

Tip: Perform a GxP impact assessment early to determine whether validation is required. 

2. Requirements Definition 

A Requirements Specification should clearly capture intended use and critical functions. Requirements must be testable, traceable, and approved. Collaboration with end-users ensures practical coverage from those deliverables. 

Based on the system complexity and level of risks, often reflected by its GAMP 5 category, determine the type of system specifications that will be required. Here, it is important to understand the use and differences between a User Requirements Specification (URS), describing what the system must do and owned by the regulated company, and a functional and design specification (FS/DS), describing how the desired behavior is archived and typically provided by the vendor. 

Tip: Collaborate closely with end users and subject matter experts (SMEs) to ensure the requirements reflect real-world scenarios. 

3. Supplier Assessment 

When relying on vendors, assess their development practices, regulatory awareness, and support. For critical systems, audits or audit reports are advisable. Keep records of supplier qualification as part of your validation file. 

• Evaluate the vendor’s GxP understanding, development methodology, and support capabilities. 

• Request documentation on SDLC (Software Development Life Cycle), testing, and change control. 

• Align the extent of reliance on supplier documentation with the supplier’s risk classification — low-risk suppliers may reduce internal effort, while high-risk suppliers require additional end-user validation. 

• For high-risk or critical systems, perform vendor audits or request audit reports. 

  
  

Tip: Maintain a supplier qualification record as part of your validation package. 

4. Design Review and Risk Assessment 

We mentioned before that validation activities should be proportional to the level of risk a system represents. This step is performed to ensure the system functions as intended and that risks are appropriately mitigated: 

• Perform a Functional Risk Assessment (FRA) to rate functions by criticality, complexity, and likelihood of failure: 

  • Criticality of the function (impact on patient safety, product quality, data integrity). 

  • Complexity of the software and its configuration/customization. 

  • Likelihood of failure, based on maturity of the function and how it is implemented. 

    
    

These factors can be used to classify risks as High/Medium/Low, which then directly drive the testing depth and validation evidence required. It reflects GAMP 5 (2nd Edition) risk principles and FDA CSA guidance. Risks found to be at an unacceptable level are usually addressed in one of three ways: by implementing additional technical controls, by implementing new procedural controls, or by performing additional testing. 

• Implement controls aligned with risk mitigation strategies. 

• Establish traceability between specification elements (requirements, functions and design elements). 

  
  

Tip: Document rationale for testing decisions based on risk prioritization. 

5. Testing & Verification 

Validation protocols for software validation typically include: 

• Installation verification: Verify installation requirements are met, and the system is configured as specified. 

• Functional verification: Verify functionality under defined conditions. 

• User acceptance testing: Verify performance in the real-world setting, from an end user perspective. 

  
  

Apply a risk-based testing approach. High-risk functions require rigorous scripted testing, including negative testing and challenging scenarios. Lower-risk functions may rely on exploratory or unscripted testing (e.g., ‘day-in-the-life’ scenarios), supported by CSA critical thinking. 

Tip: No matter the type of testing performed, testing should be traceable to specification elements and test errors/deviations should be managed (defined, investigated, corrected and formally documented). 

6. Release & Change Control 

Software should only be released once all validation activities are: 

• Completed, reviewed, and approved by Quality. 

• Documented in a validation summary report, highlighting outcomes, deviations, and resolutions. 

  
  

After release: 

• Apply formal change control procedures for updates or patches to your validated system. 

• Perform impact assessments and retesting as necessary. 

• Ensure end users and administrators are trained on the validated system, including all relevant procedures, data integrity responsibilities, and change control processes based on their system role. 

  
  

 Tip: Establish a defined "state of control" and ensure any deviations are captured in change history logs. 

7. Ongoing Monitoring 

Validation is not a one-time event, it is a continuous process: 

• Implement a Periodic Review SOP to define how to reassess validated systems, including system changes, vendor documentation (SOC 2 Type II, ISO 27001), and overall compliance status. 

• Monitor system performance, user incidents, audit trails, and error logs. 

• Solicit user feedback to identify usability gaps or recurring issues. 

• Perform periodic reviews to reassess the validation status and confirm continued fitness for intended use. 

  
  

Tip:  Use a formal SOP to guide periodic reviews. Reassess new enhancements, vendor certifications (e.g., SOC 2 Type II, ISO 27001), and system performance to maintain the validated state in line with GAMP 5 and CSA principles. 

Common Mistakes and Solutions 

Pitfall	Risk	Mitigation
Incomplete requirements	Software fails to meet business needs	Invest time in thorough URS development
No risk-based approach	Excessive or insufficient validation	Use GAMP 5 principles
Vendor reliance without verification	Over-trust in supplier documentation	Conduct internal validation and audits
Lack of traceability	Gaps during audits or inspections	Use traceability matrices from URS to test cases
Poor documentation	Regulatory non-compliance	Ensure clarity, completeness, and approvals

Trends Shaping Software Validation 

• Cloud-based solutions, because they imply shared responsibilities between the life sciences organization and the Cloud Service Provider (CSP), demand special attention to security, data ownership, and vendor accountability. 

• Agile development calls for validation strategies aligned with iterative releases. 

• Artificial Intelligence (AI) /Machine Learning (ML) systems require ongoing performance checks and explainability measures. 

• Computer Software Assurance (CSA), an FDA initiative, promotes smarter, risk-driven validation emphasizing critical thinking over excessive paperwork. 

Final Thoughts: Make Validation a Quality Enabler 

Software validation should not be a one-time compliance exercise but an ongoing lifecycle activity that strengthens your product, processes, and quality culture. With the right approach, validation builds trust, efficiency, regulatory compliance and operations resilience. 

Success today requires more than testing, it means applying risk awareness, clear documentation, and CSA-driven critical thinking across the lifecycle: from planning and supplier qualification to change control, periodic reviews, and ongoing vendor oversight. 

Whether you are validating SaMD, implementing a LIMS, or deploying a QMS platform, the most effective strategies balance robust testing where risk is high with streamlined assurance where risk is low. This risk-based mindset, aligned with GAMP 5 (2nd Edition) and FDA CSA guidance, ensures that validation is not just a regulatory requirement, but a business enabler that prepares you for the future of cloud, SaaS, and AI-enabled systems. 

Need Help? 

Our experienced GxP consultants bring decades of hands-on validation experience across pharma, biotech, and medical device sectors. Whether you need to establish a full validation framework or just validate a single tool, we’re ready to help. 

For more expert insights on validation, compliance, and GxP best practices, stay tuned to our blogs. Have a topic you want us to cover? Let us know.