Computer System Validations &

Regulatory Requirements

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 Computer system validation (sometimes called computer validation or CSV) is the
process of documenting that a computer system meets a set of defined system
requirements. Validation of computer systems to ensure accuracy, reliability,
consistent intended performance, and the ability to discern invalid or altered records
is a critical requirement of electronic record compliance, as described in the FDA 21
CFR 11.10(a) and EMA Annex 11, Section 4.

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 Computer System Validation (CSV) is a process used to ensure (and document) that
a computer-based systems will produce information or data that meet a set of
defined requirements. If a system meets these requirements, it can be assumed that
it is consistently performing in the way it was intended.

The process is used to replace paper with electronic data within highly regulated
environments that directly impact public health and safety and make sure the system
is completely transparent, robust and tamper proof.

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 History
 The concept of validation was derived from engineering principles of validation of mechanical
system that has been extended to the software industry.
 To extend it further during mid-1970’s, Ted Byers and Bud Loftus, two Food and Drug
Administration (FDA) officials first proposed the concept of validation in order to improve the
quality of pharmaceuticals (Agalloco 1995).
 Feeling the necessity of Validation, FDA published a guide to the inspection of Computerized
Systems in Pharmaceutical Processing, also known as the ‘bluebook’ (FDA 1983).
 In 1987 the FDA published a document entitled ‘FDA Guidelines on General Principles of Process
Validation’.
 For MHRA this is Annex 11 of the EU GMP regulations (EMEA 1998), whereas for American FDA,
this is 21 CFR Part 11 for rules on the use of electronic records, electronic signatures (FDA
1997).
 FDA issued final part 11 regulations In March of 1997, became effective in August 1997 &
Revised in August 2003

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 Need for Computer System Validation
 This is an era where we are surrounded by computer systems everywhere, It is extremely
important to validate the computer and IT systems as it makes sure that all the concerned IT
applications are fulfilling their intended purposes. Validation helps in controlling different phases of
development, design, testing and routine of the software that is being used by the IT system during
its life cycle. As long as the computer system is running accurately, you can be assured that all the
information and reports that they store remain safe.

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 Need for Computer System Validation (Contnd..)
Now a day’s several regulatory bodies have incurred the specific requirement for computer system
validation as follows, but not limited to:

USA:
 FDA 21 CFR 58, GLP for non-clinical Laboratory Studies
 FDA 21 CFR 211 Current Good Manufacturing Practice for Finished Pharmaceuticals Subpart
D‐Equipment, Sec. 211.68(b)
 21 CFR 1271 Human Cells, Tissues, and Cellular and Tissue‐Based Products Subpart D Current
Good Tissue Practice, Sec. 1271.160(d)

USP:
USP <1058> Analytical Instrument Qualification

ICH:
 ICH Q7A, Good Manufacturing Practice for Active Pharmaceutical Ingredients
 ICH E6 Good Clinical Practice

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 Need for Computer System Validation (Contnd..)
Now a day’s several regulatory bodies have incurred the specific requirement for computer system
validation as follows, but not limited to:

Brazil:
 Title VIII Good Phytotherapic Medicaments Manufacture Practices, Chapter IV Validation, Art. 18.
 Title VII, COMPUTER INFORMATION SYSTEMS, Art. 573.

PIC/S:
 PE 005‐3 GMP Guide for Blood Establishments Section (9.8)
 PE 009‐11 Guide to Good Manufacturing Practices for Medicinal Products (5.40)
 PE 011‐1 Guide to Good Distribution Practice for Medicinal Products

WHO:
 WHO Specifications for Pharmaceutical Preparations (6.3)
 WHO Good Manufacturing Practices for Pharmaceutical Products: Main Principles (4.11)

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 Result of violations to Regulatory compliance
Several regulators mandate the need to perform Computer System Validation and these regulations
have the impact of law. Whereas, failing an FDA audit can result in FDA inspectional observations
(“483s”) and warning letters. Failure to take corrective action in a timely manner can result in failure
to accept the GxP data, shutting down manufacturing facilities, consent decrees, and stiff financial
penalties.

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 Why validation required
 To reduce the risk and legal liability
 To safeguard the data integrity in regulated environment
 To ensure the safety of system for quality of the product & health of the patients
 To get confidence in data produced by the system
 To ensure and compliance with regulations
 To assure “Inspection Readiness”
 To ensure that the computer systems are correct for their intended use and operating properly
represents a good business practice
 To generate the objective evidence to produce documented evidence which provide high degree of
assurance that the system is consistent to produce the results.
 Software is constantly evolving to keep up with the increasingly complex needs of the people that
use it

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 Good Automated Manufacturing Practices (GAMP)
GAMP stands for Good Automated Manufacturing Practice. A risk based compliant approach to GxP
computerized systems. There are four categories of software as stated in GAMP5. Depicted below is
the pictorial presentation of transformation from GAMP4 to GAMP5 with illustration of categorical
benefits:

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 Validation of Computer System
The pragmatic risk-based approach to compliant GxP Computerized system provides to achieve
system that are fit to intended use in an efficient and highly effective manner. A more flexible risk-
based approach to compliant GxP systems based on scalable specifications and verification approach
has been applied to the computer systems available in the GxP environment. This approach relies
heavily on having a robust quality risk management system. GAMP-5's approach can be summed up
by the V-model diagram (V-Model Diagram is available in the next slide)

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 Validation of Computer System (Contd..)

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 Life cycle approach of a computer system
 A software application or a computerized system needs to be planned and implemented. Therefore,
the use of a system life cycle is important as it provides a plan to use as a basis for the
implementation or building of a computerized system.
 The key requirement of any life cycle model used is that it should be meaningful and applicable to
the system that you are building or implementing. CSV is interlinked very closely with the software
development life cycle considering that it is conducted at every stage of SDLC.

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 Life cycle approach of a computer system (Contd..)
The lifecycle of a computer system is comprised of different sub-projects within the lifecycle phase: in
Concept, assessments are done, validation plans are developed, scripts are written, and governance
processes are formalized. Upon release to Operation, the system is monitored, applying any changes
using change control through system Retirement.

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 Overview of GAMP documentation structure
 The GAMP guidance aims to achieve computerized system that are fit for intended use and meet
current regulatory requirements, by building upon existing industry practice in an efficient and
effective manner. The GAMP guide contains the validation framework and associated procedures
and guideline.
 The pyramid shown in the next slide defines the comprehensive body of knowledge covering all
aspects of computerized system good practices and compliance.

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Overview of GAMP documentation structure (Contd..)
GAMP5 A Risk based approach to compliant GxP Computerized System

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CSV implementation documentation requirements

To implement effective computer system validation in GMP environment following is the

documentation requirement, but not limited to this:
 Vendor Assessment
 User requirement specification
 Functional requirement specification
 Validation Plan
 Validation requirement specification
 Validation Traceability Matrix

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CSV implementation documentation requirements
(Contd…)
 Network and infrastructure qualification
 Installation qualification scripts and results
 Performance qualification scripts and results
 Operational qualification scripts and results
 Validation report
 System release certificate

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Data requirements (ALCOA+ requirements)

 An effective data integrity governance system is required to establish by every organization which
will demonstrate Management’s understanding and commitment to reliable data governance
practices including the necessity for a combination of appropriate organizational culture and
behaviors and an understanding of risk associated to data and data lifecycle.
 The key principles of any documentation has been clearly specified by regulators set forth for
both paper and electronic-based record keeping and summarized by the acronym ALCOA
(Attributable, Legible, Contemporaneous, Original, and Accurate) which have been extended by
adding the other attributes (Complete, Consistent, Enduring and Available) now termed ALCOA+.

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Data requirements (ALCOA+ requirements)Contd…

 Personnel at all level shall be educated about the expectation of ALCOA+ to ensure that the
events are properly documented, and data can be used to support informed decisions. The
communications shall set forth to require open reporting of violations observed by operators to
the relevant responsible persons and to allow personnel to recommend improvements oriented to
prevent data falsifications. This reduces the incentive to falsify, alter or delete data.
 Data supremacy is the sum of all measures which provides assurance of data integrity. All the
aforementioned key principles of documentation need to be well taken care in computer system
validation by safeguarding the data integrity in regulated environment which ensures the
compliance with regulation and get confidence in data produced by the system.

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Quality Risk Management
Quality risk management (QRM) is an essential tool applied for an effective data Management
Program. The effort and resources assigned to data and record management shall be proportionate
with the risk: the risk-based approach to record and data management shall ensure that adequate
resources are allocated and that control strategies for the assurance of the integrity of GMP data
are commensurate with their potential impact on product quality and patient safety and related
decision-making.
As not all data or processing steps have the same importance to product quality and patient safety,
risk management shall be utilized to determine the importance of each data/processing step.

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Quality Risk Management (Contd…)
An effective risk management approach to data governance shall be based upon Risk to Data
Integrity determined by the following factors:
 Data criticality (impact to decision making and product quality)
 Exposure to violation (opportunity for data alteration and deletion, and likelihood of detection /
visibility of changes by the manufacturer’s routine review processes). The exposure is determined
by the potential to be deleted, amended or excluded without authorization and the opportunity
for detection of those activities and events.
The risks to data may be increased by complex, inconsistent processes with open-ended and
subjective outcomes, compared to simple tasks that are undertaken consistently, are well defined
and have a clear objective

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Conclusion
In order to fulfill the regulatory requirement & compliance standards for successful regulatory
inspection; Computer system validation is an important tool to establish and maintain data integrity
controls though out the data life cycle. Data integrity is essential tool to offer adequate confidence
to regulatory bodies on data associated to manufacturing and testing process at each non-clinical
testing facility/pharmaceutical firm. Computer system validation approach of non-clinical testing
facility/pharmaceutical manufacture should be implemented in line with GAMP 5 guideline to confirm
21 CFR Part 11 and other major regulatory compliance.

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Contact us…
Contact us for any support for the on-site, off-site CSV assistance.

[email protected] 306-715-9460

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