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The Importance of Computer

An Executive
System Validation for
Summary Regulated Systems
Insights into Computer System Validation (CSV) for
businesses that operate in regulated environments.

Jim Willis Data integrity is becoming an increasingly common focus area in all regulated analytical
Global Compliance laboratories. Regulators are evaluating the workflow of how the software is configured and
Program Manager
Agilent Technologies, Inc. used against the technical and procedural controls that have been implemented. As a result,
there is renewed attention on the fact that computerized systems must be validated for their
intended use and on computer system validation requirements. This article provides insights
into Computer System Validation (CSV) such as what it is, why it is important for laboratories
to perform CSV, and what laboratories need to know about the regulations for data integrity
such as 21 CFR Part 11 (Electronic Records and Signatures). This article focuses on the ISPE
Good Automated Manufacturing Practice (GAMP® 5) CSV Life Cycle V Model and risk-based
approach to CSV for regulated applications.
Michael Korbel
Senior Compliance Consultant
Agilent Technologies, Inc. What is CSV and Why is it Important? Validation is a lifecycle approach. Whenever
Validation is defined as: a new system is put into a regulated environ-
The establishment of documented ment, as part of its commissioning, full system
evidence that provides a high de- validation must first be completed. Once in
gree of assurance that a system place, the system will fall under change control
or process will consistently meet and will require revalidation based on changes
predetermined user specifications that are made to the system. Each change
(intended use). must be evaluated to assess the risk level and
how much revalidation would be required on
Validation of computerized systems is that system. Finally, when a system comes to
required to comply with regulations in the the end of its lifecycle and is retired or decom-
pharmaceuticals, medical devices, food, and missioned, all the records for that system must
dietary supplements industries. It is one of the be consolidated and remain available in the
foundations for creating a strong data integrity future for any type of audit or investigation.
compliance program by ensuring that data
and test results cannot be manipulated, falsi- Regulations and Guidance Documents
fied, or accessed by unauthorized personnel. Several different regulations and guidance
Validation is also a foundation of good science documents ser ve as the basis for the
in that it ensures the reliability of data. requirements for validation of computerized



systems. These include the Regulations

Figure 1: Regulationsand Guidance
and Guidance Documents.
predicate regulations, FDA
21 CFR Parts 210/211 (GMP) •  FDA 21 CFR Parts 210/211 (GMP) and 58 (GLP) – Predicate Rules
a n d F DA 21 C F R Pa r t 5 8 •  Sets the standard for data quality and validity – In any form (Paper or Digital)
•  Foundation for Data Integrity
(GLP), which set the standard
for data quality and validity in •  FDA
•  Electronic Records Security – User Access / Permissions
any form (paper or digital) and •  Audit Trails – Who did what, when, why?
provide the foundation for data •  Data Back-up / Archive / Retrieval
integrity, and the regulations for •  Disaster Recovery
•  Login / Password Security
electronic records and electronic •  Data Integrity
signatures, FDA 21 CFR Part 11 •  Electronic Signatures

and EU Annex 11, which provide •  Data Integrity

the requirements for electronic •  FDA Data Integrity Guidance (2018)
•  MHRA Draft GxP Data Integrity Guidance (2018)
records security, audit trails,
•  ISPE : GAMP Records and Data Integrity Guide
back-up/archive/ retrieval of
•  GAMP 5 – Guideline for CSV
data, disaster recovery, login/
•  Risk Based Approach and V Model documents
password/permissions security,
•  Universal process for validating computerized systems
and electronic signatures. GAMP 5 – CSV Life Cycle (V Model)
In addition, key regulatory
guidance documents include Figure 2: GAMP 5 CSV Life Cycle V Model.
the FDA Data Integrity Guidance 8 March 15, 2019 Confidentiality Label

(1), the MHRA GxP Data Integrity Site Validation Master Validation
Plan Summary
Guidance (2), and the ISPE GAMP Assessment
A VMP is the foundation for the validation program and should
Records and Data Integrity Guide include process validation, facility/utility qualification & validation,
equipment qualification, cleaning validation and computer
(3), which provide additional Validation Plan
validation. Traceability
guidance on complying with
data integrity. Finally, there is the
GAMP 5 Guideline for CSV (4), User Testing of
Requirements Qualification
which outlines a universal, risk-
based approach for validating
Functional Operations SOPs, User
computerized systems (Figure 1). Requirements
Testing of
Qualification Training

GAMP 5 CSV Life Configuration/

Cycle V Model Design
Testing of
The GAMP 5 CSV Life Cycle
V Model for CSV is a guid- Data Integrity is built into the Requirements and Specifications
Compliance Consulting Services – Computer System Validation (CSV)
ance document published by so the system is Configured and Tested properly.
the International Society for
Pharmaceutical Engineering 9 March 15, 2019

(ISPE) that was developed based on input from industry pro-

fessionals. The framework outlined in this document provides
a comprehensive approach to CSV that is generally accepted
within the industry and is in line with the application of US and
The GAMP 5 CSV Life Cycle V Model “
European regulations governing CSV and data integrity. for CSV is a guidance document pub-
The GAMP 5 V Model is illustrated in Figure 2. Shown are
the various documents that are developed when following this lished by the International Society for
approach in a CSV project.
Pharmaceutical Engineering that was
Risk Assessment. Starting in the upper left-hand part of
the V, the first step is to perform a Risk Assessment. The developed based on input from industry
purpose of the Risk Assessment is to determine which
regulations are applicable to the system and to assess the
level of risk (e.g., critical, high, medium, or low) with respect
professionals. ”
to product quality (e.g., impact on safety, identity, quality,


GAMP 5 Approach – Risk Assessment (RA)

A Risk-Based Approach to CSV Utilizing GAMP 5
efficacy, purity, or decisions Figure 3: GAMP 5 Approach – Risk Assessment.
related to product release).
The level of risk will determine
Perform a risk assessment to evaluate the regulatory risks related to the System’s intended use
the degree of validation testing
• Determine which regulations are applicable to the system and its data
required. For example, a chro-
• Determine level of risk (Critical, High, Medium, or Low) that is applicable to your system’s
matography data system that is use and data
used to assay a finished drug
product for the active ingredient Critical Risk: Direct impact on product safety, identity, quality, efficacy, purity or effect
in the product would be consid- decisions relating to product release.
Validation is required.
ered a critical-risk system with
High Risk: Indirect impact on product safety, identity, quality, efficacy, purity or effect
direct impact on product quality. decisions relating to product release.
A fairly comprehensive validation Validation is required.–Testing may not have to be as comprehensive.
effort would be required. By Medium Risk: No perceived impact on product (safety, identity, quality, etc.) or effect decisions
relating to product release.
comparison, a water purification
Validation is suggested.
system used to prepare testing
Low Risk: Failure of the system is limited to a non-essential business process.
samples would be a high-risk Validation not required. Qualification or Verification recommended.
system with an indirect impact
on product quality. Validation 13 March 15, 2019 Confidentiality Label

certainly would be required, but the testing may not need to be The URS captures the intended use of the system, including
as comprehensive as for the critical-risk system. A medium-risk the business capability to be executed. In developing the URS,
system, where there is no perceived impact on product quality, it is important that the user requirements are focused on
may only require hardware qualification and verification of the ensuring that the system is designed, configured, and used in
software. A low-risk system would be one where the failure a manner that is consistent with scientific methods, SOPs, and
of the system would be limited to a non-essential business regulations. The user requirements should be high level and
practice. Validation would not be required, but qualification or not at a functional level, which is more appropriate for the FRS.
verification would be recommended (Figure 3). The FRS describes the technical solution for how the
system meets the user requirements. For example, the FRS
Validation Plan. Next, a Validation Plan is issued to document may indicate how a button or menu item would address a
the overarching plan for the project. A typical Validation Plan specific function described in the URS, or it may document
includes the following: how a parameter must be populated. In many cases, there
• overview of the system are multiple functional requirements mapped back to a single
• objectives of the validation project user requirement.
• scope of the system (i.e., the number of The next document would either be a CS, which is gen-
servers and clients, the type of software erally created for a Commercial Off-The-Shelf system, or a
and version of the software application, DS, which would be created for customized software. At a
and any associated instrumentation) minimum, both documents should describe the following:
• roles and responsibilities of the functions • system architecture
involved, including the system owner • required hardware and software components,
• list of applicable references (i.e., regulations, including the version numbers of the application
and internal policies and SOPs) software and any ancillary software, like
• validation rationale and testing strategy (e.g., Internet Explorer or Adobe PDF
application of the GAMP 5 model) • date and time settings and format
• results of the completed Risk Assessment • access and security settings
• list of deliverables (e.g., individual validation • login parameters
documents, SOPs, and training materials) • audit trail settings
• project milestones • any other configurable settings needed to
• acceptance criteria for system release meet user requirements (e.g., data backup and
restore processes, system recovery process,
Requirements. The next set of documents cover the specifi- or instrument communication settings)
cation phase and include the User Requirements Specification
(URS), Functional Requirements Specification (FRS), and Testing. The next is the testing phase, which includes the
Configuration Specification (CS) or Design Specification (DS) Installation Qualification (IQ) Operations Qualification (OQ),
documents. Together, these documents define what the and Performance Qualification (PQ). IQ involves testing of the
system will do and how it will be built. configuration settings and specifications, OQ involves testing


of the functional requirements, GAMP

Figure 4: GAMP 5 Approach – Traceability
5 Approach – Traceability Matrix. Matrix
and PQ involves testing of the
user requirements to make •  The Trace Matrix (TM) will show the relationship between:
sure the system allows the end User Requirements => Functional Requirements => Configuration Specifications
users to perform their workflow •  The TM also maps requirements to testing:
through the application the way Configuration Specifications => IQ
Functional Requirements => OQ
they need it to work. For each
User Requirements => PQ
phase of testing, a protocol
•  The Trace Matrix should be completed and approved along with the PQ Protocol, or with the
is needed to describe, at a Validation Summary Report. Better to approve before all testing is completed to ensure that all
minimum, the objectives and requirements were properly covered by testing.

scope of the protocol, roles and

responsibilities of the testing
team, and the strategy for how
the test scripts will be executed.
There should be instructions for
how to execute test scripts (i.e.,
good documentation practices).
There also should be a signature
identification page, so that anyone involved in the execution of services, which include CSV – GAMP 5 process, data integrity
the test scripts can be identified, deviation report forms and audits and remediation, custom procedure writing, and more;
18 March 15, 2019 Confidentiality Label

a deviation log, and an amendment form to update the test validation starter kits; and execution services (5).
script, if necessary. It should be noted that the terms OQ, OQ
and PQ have different interpretation in a software validation Conclusion
and analytical instrument context. In summary, the focus on data integrity is driving a renewed
evaluation of how regulated laboratories use software in the
Traceability Matrix. To ensure that all of the system specifica- work they do. It is an increasingly common focus area in
tions are tested, a Traceability Matrix is needed to map the regulated analytical laboratoryies audits. To ensure compli-
various requirements in the URS, FRS, and CS documents ance with regulations for data integrity, computerized systems
to the testing performed in the IQ, OQ, and PQ testing. In must be validated for their intended use. In simple terms, this
addition, standard operating procedures (SOPs) must be means that the way the laboratory has configured and use
implemented for system use, administration, maintenance, the software must be challenged in the validation work. The
and training (Figure 4). GAMP 5 CSV Life Cycle V Model for CSV provides a universal,
risk-based approach to CSV. The framework outlined in this
Validation Summary Report (VSR). Finally, upon completion guidance document provides a comprehensive approach to
of the qualification testing, a VSR is issued to summarize the CSV that is generally accepted within the industry and is in line
execution of the validation project and to document any devia- with the application of US and European regulations governing
tions or failures that occurred and how those were dealt with. CSV and data integrity. Application of this risk-based approach
The VSR should list all of the documents created to validate to CSV will ensure that the CSV effort will be most efficient
the system, the testing results in a pass/fail status fashion because the degree of testing performed will be commensu-
for each of the IQ, OQ, and PQ test scripts, any deviations rate with the degree of risk.
encountered during testing, and the corresponding corrective
action to close each of those deviations. Before production References
use, all system-related SOPs must be approved and effective 1. FDA, Guidance for Industry-Data Integrity and
and the end users must be trained on these before they can Compliance with Drug CGMP, December 2018.
use the system. Release of the system for use either can be 2. MHRA, ‘GXP’ Data Integrity Guidance
and Definitions, March 2018.
based on approval of the VSR or on a memo of release.
3. ISPE, ISPE GAMP Guide: Records and

Data Integrity, March 2017.

Solutions 4. ISPE, Good Automated Manufacturing Practice
Agilent CrossLab provides services to help customers meet (GAMP) Guidelines, Version 5, International Society
their compliance needs. Available are compliance consulting for Pharmaceutical Engineering, February 2008.
5. www.agilent.com/chem/compliance-consulting