Why Computer Validation ?

List of Guidance Documents.

General Principles of Software Validation.

OTS Software Use in Medical Devices.

Electronic Records, Electronic Signatures ( 21 CFR Part 11 )

Guidance Document for Computerized System used in Clinical Trials.

Validation of Electronic Spreadsheet.

Introduction to Validation Master Plan.

Definition of ERP System

Possible Questions

References

Data and Information Management Systems

Problem Solving Applications
Communication Aids ( e- MAIL, DIMS )
Laboratory
Automation
MICROBALANCES )

LIMS,

HPLC,

DISSOLUTION,

Process Control
Computerised System used for Clinical Trials and Manufacturing of
Medical Devices

April 1999

Computerized Systems Used in

Clinical Trials

September 1999

Off-The-Shelf Software Use in

Medical Devices

August 2001

Electronic Records; Electronic

Signatures Validation

January 2002

General Principles of Software

Validation

August 2003

Electronic Records; Electronic

Signatures - Scope and
Application

21 CFR Part 11

Electronic Records; Electronic

Signatures

21 CFR Part 820

Quality System Regulation

 Software used as a component, part, or accessory of a

medical device
Software that is itself a medical device
Software used in the production of a device
Software

used in implementation of the device

manufacturer's quality system

January 11, 2002,

CDRH, CBER

Postchange Software Validation

Documentation Updation

Least Burdernsome and Specific Approach

Validation during each activity of
life cycle model

Premarket Submission to :
ODE
CDRH
CBER
Validation Master Plan

Self-Validation not followed

Validation Documentation

21 CFR Part 820

SOFTWARE
VALIDATION

OTS Software Validation

(device manufacturer
responsible)

Simulated Use Environment and

User Site Testing
Overall design validation for the system
Validation Coverage / Extent of Validation

 Quality Planning

System Requirements Definition

Detailed Software Requirements Specification
Software Design Specification

Construction or Coding
Testing
Installation

Operation and Support

Maintenance
Retirement

Guidance for premarket submission to FDA

3 Level of Concerns
Documentation ( Basic and Special)

Corneal Topographer (Minor Level of Concern Device)

Implantable Medical Device Programmers (Major Level of Concern
Device)

September 9, 1999

21

Was issued in March 1997

C
F
R

Records in electronic form that are created,

modified, maintained, archived, retrieved, or transmitted

P
A
R
T

Submission to FDA and also to comply with Predicate Rules

(The Act ,The PHS Act)

Three major concerns demanded the revision of 21 CFR Part 11

1. unnecessarily restrict the use of electronic technology

2. significantly increase the costs of compliance
3. discourage innovation and technological advances
Revised and issued in August 2003

11

WHAT DOES PART 11 REQUIRE

Records maintained in electronic format in place of paper format

(PredicateRules and FDA)
No predicate rule requirement but it is in electronic format --- No CFR Part 11
Records maintained in electronic format in addition to paper format
(Predicate Rules and FDA)
Records maintained in electronic format
(Predicate Rules, but not required by FDA)
Electronic Record used for generating submission if not required by Predicate
Rules is not a part of CFR Part 11 and vice versa

Electronic signatures that are intended to be the equivalent of handwritten

signatures, initials, and other general signings (Predicate Rules)

Validation
Audit Trail

Legacy Systems
Copies of Records
Record Retention

System Requirements Specifications

Documentation of Validation Activity
Dynamic Testing
Static Verification Techniques
Extent of Validation
Independence of Review
Revalidation

 Documentation of user requirements/intended use

Computer system implements needs correctly

Documentation of Validation Activity

Validation Plan
Validation Procedure
Validation Report

 Key testing consideration

Testing Condition
Normal
Stress
Actual Performance Testing
Simulation Test
User-Site Test
Software testing
Structural Testing (White Box Testing)
Functional Testing (Black Box Testing)
Program Build Testing

 Static analyses
Technical reviews

Extent of Validation
Risk with the system

Systems Complexity

 Third Party
Person of the Organisation

Revalidation
As per requirement of user
By system upgradation
During routine servicing and maintenance
Network like internet

IS IT NECESSARY TO VALIDATE COMPUTERIZED

SYSTEMS USED IN CLINICAL TRIALS

April 1999

USFDA

 Automating analytical data calculations from various laboratory

analyses
Tracking and summarizing product complaints
Gathering and summarizing clinical trial data collection and

analyses
Validation of Electronic Spreadsheet is necessary in order to evaluate

key drivers : Authenticity, Data and System Integrity, and

Confidentiality
Should comply with Predicate Regulations

21 CFR Part 11

ELECTRONIC
SPREADSHEET

YEAR OF DEBUT

LAUNCHER

VisiCalc

1978

Harvad Business School

Lotus 1-2-3

1983

IBM

Excel

1984

Microsoft Corporation

Preparation of test cases/test procedures for each functional

element defined. Test case must challenge the operation and
performance of the system especially for its most critical
parameters
Execution of the test cases and the results must be recorded
Evaluate whether software has been validated for its intended
use
Documented evidence of all testing procedures, test input data,
and test results must be retained

 "HOW MUCH VALIDATION IS ENOUGH ?"

"WHICH SYSTEMS DO WE HAVE TO VALIDATE ?
HOW TO COORDINATE THE VALIDATION EFFORTS ?
HOW TO MAKE VALIDATION EFFORT WITHIN THE

BUDGET ?

 Integrates planning, manufacturing, distribution, shipping, and accounting

into a single system

Designed to serve the needs of each different department within the

enterprise

Creates supply chain management

An ERP implementation can cost millions of dollars to create, and may take

several years to complete

Implement ERP in a more incremental fashion

Tremendous advantages:

1. Share information
2. Workflow becomes more automated
3. It can speed up the manufacturing process by automating
processes and workflow
4. It also reduces the need to carry large inventories.

 According to your view point, Why it is necessary to validate

Computer ? [ 2 marks ]
State the general principles of Software Validation. [ 5 marks ]
What is OTS Software ? How the level of concern affect the

documentation of OTS software validation ? [ 2 marks ]

State the key principles of validating Electronic Records and Electronic

Signatures. [ 5 marks ]
How will you validate the Electronic Spreadsheet ? [ 2 marks ]

General Principles of Software Validation; Final Guidance for Industry and

FDA Staff, January 11, 2002.
(http://www.fda.gov/cdrh/comp/guidance/938.html)
Guidance for Industry, FDA Reviewers and Compliance on Off-The-Shelf
Software Use in Medical Devices, September 9, 1999.
(http://www.fda.gov/cdrh/ode/guidance/585.html)
Guidance for IndustryPart 11, Electronic Records; Electronic Signatures Scope
and Application, August 2003.
(http://www.fda.gov/cder/guidance/5667fnl.htm)
Guidance for Industry 21 CFR Part 11; Electronic Records; Electronic Signatures
Validation, August 2001.
(http://www.fda.gov/ohrms/dockets/98fr/001538gd.pdf )
Guidance for Industry, Computerized Systems used in Clinical Trials, April
1999.
(http://www.fda.gov/ora/compliance_ref/bimo/ffinalcct.htm)

US Food and Drug Administration, Center for Devices and Radiological

Health, Code of Federal Regulations, Title 21, Part 11, Volume 1, Electronic
Records and Electronic Signatures, Revised as of April 1, 2005
(http://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfcfr/CFRSearch.cfm?CF
RPart=11&showFR=1)
Computer Validation Guide, Final Draft, Version 2, December 2002.
(http://apic.cefic.org/pub/compvalfinaldraftDecember2002.pdf)
Technical Considerations for the Validation of Electronic Spreadsheets or
Complying with 21 CFR Part 11 by Taun T. Phan, Pharmaceutical Technology,
January 2003.
(www.pharmtech.com)
Computer Validation Master Planning Validation Strategies by Michael
Schousboe,
Pharmaceutical
Technology,
November
1,
2005.
(www.pharmtech.com)
Computers in Pharmaceutical Technology, Encyclopedia of Pharmaceutical
Technology, Volume 3.