SEMINAR ON,

1
SEMINAR ON,
COMPUTER VALIDATION

• 
  PRESENTED BY,
• POONAM Y AGHARA
• M PHARM
• 
  DEPT. OF PHARMACEUTICS AND PHARMACEUTICAL
  TECHNOLOGY
• 
  L. M. COLLEGE OF PHARMACY
• 
  AHMEDABAD

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OUTLINES .....

• 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

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WHY COMPUTER VALIDATION
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COMPUTER APPLICATIONS

• Data and Information Management Systems
• Problem Solving Applications
• Communication Aids ( e- MAIL, DIMS )
• Laboratory Automation ( LIMS, HPLC,
  DISSOLUTION, MICROBALANCES )
• Process Control
• Computerised System used for Clinical
  Trials and Manufacturing of Medical Devices

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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
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GENERAL PRINCIPLES OF SOFTWARE VALIDATION

• 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
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GUIDELINE SAYS ..
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SOFTWARE LIFE CYCLE MODEL

• Quality Planning
• System Requirements Definition
• Detailed Software Requirements Specification
• Software Design Specification
• Construction or Coding
• Testing
• Installation
• Operation and Support
• Maintenance
• Retirement

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OTS SOFTWARE USE IN MEICAL DEVICES

• 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
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OTS SOFTWARE DECISION SCHEMATIC
11
ELECTRONIC RECORDS ELECTRONIC SIGNATURES
21 C F R
P A R T
11

• Was issued in March 1997
• Records in electronic form that are created,
• modified, maintained, archived, retrieved,
  or transmitted
• 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

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• WHAT DOES PART 11 REQUIRE

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21 CFR PART 11 applicable for..

• 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)

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APPROACH TO SPECIFIC PART 11 REQUIREMENTS . . . .
.

• Validation
• Audit Trail
• Legacy Systems
• Copies of Records
• Record Retention

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Key Principles of Validating Electronic
Recordkeeping Computer Systems

• System Requirements Specifications
• Documentation of Validation Activity
• Dynamic Testing
• Static Verification Techniques
• Extent of Validation
• Independence of Review
• Revalidation

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System Requirements Specifications

• Documentation of user requirements/intended use
• Computer system implements needs correctly
• Documentation of Validation Activity
• Validation Plan
• Validation Procedure
• Validation Report

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Dynamic Testing

• 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

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Static Verification Techniques

• Static analyses
• Technical reviews
• Extent of Validation
• Risk with the system
• Systems Complexity

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Independence of Review

• Third Party
• Person of the Organisation
• Revalidation
• As per requirement of user
• By system upgradation
• During routine servicing and maintenance
• Network like internet

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• IS IT NECESSARY TO VALIDATE COMPUTERIZED SYSTEMS
  USED IN CLINICAL TRIALS

USFDA
April 1999
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VALIDATION OF ELECTRONIC SPREADSHEET

• 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

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HISTORY OF ELECTRONIC SPREADSHEET
ELECTRONIC SPREADSHEET YEAR OF DEBUT LAUNCHER
VisiCalc 1978 Harvad Business School
Lotus 1-2-3 1983 IBM
Excel 1984 Microsoft Corporation
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VALIDATION STEPS FOR ELECTRONIC SPREADSHEET

• 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

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ANSWERS TO

• "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 ?

VALIDATION MASTER PLAN
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ENTERPRISE RESOURCE PLANNING (ERP)

• 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.

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• 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

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REFERENCES

• General Principles of Software Validation Final
  Guidance for Industry and FDA Staff, January 11,
  2002.
• (http//www.fda.gov/cdrh/comp/guidance/938.ht
  ml)
• 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.ht
  m)
• Guidance for Industry 21 CFR Part 11 Electronic
  Records Electronic Signatures Validation,
  August 2001.
• (http//www.fda.gov/ohrms/dockets/98fr/00153
  8gd.pdf)
• Guidance for Industry, Computerized Systems used
  in Clinical Trials, April 1999.
• (http//www.fda.gov/ora/compliance_ref/bimo/
  ffinalcct.htm)

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REFERENCES

• 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?C
  FRPart11showFR1)
• Computer Validation Guide, Final Draft, Version
  2, December 2002.
• (http//apic.cefic.org/pub/compvalfinaldraftD
  ecember2002.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.

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