1. Computer System Validation
11/18/2018
Computer System Validation    
Introduction, Requirements and Tools for Implementation
Audio Seminar
September 14, 2006
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Re: Audio156

2. Today’s Agenda Q&A's Q&A's FDA and international requirements
11/18/2018
Today’s Agenda
FDA and international requirements
Terminology, master&project planning,
Specifications (DQ)
Vendor Assessment
IQ/OQ/PQ
Change control, requalification
Validation report and other documentation
10 worst mistakes
Part 1
Q&A's
Part 2
Q&A's

3. Reference material Master plan/Project Plan
11/18/2018
Reference material
Master plan/Project Plan
SOPS - Validation of COTS systems - Risk based validation - Validation of spreadsheet applications - Testing - Validation of electronic document management systems
Example: Identification of computer systems
Examples for Warning letters
FDA and other guidance documents
This material and more is available for download on the seminar website. The link is included in the order confirmation. For ordering go to:

4. Regulations and Quality Standards
11/18/2018
Regulations and Quality Standards
Good Laboratory Practices
GMP Manufacturing Practices
Good Clinical Practices
FDA’s 21 CFR Part 11 (Electronic records and signatures)
EU and FDA
Japan
(Automated) Equipment should be suitable for it’s intended use
Equipment should be routinely checked

5. Calibration, inspection, routine checks
11/18/2018
FDA GMP (211.68)
(a) Automatic, mechanical, or electronic equipment or other types of equipment, including computers, or related systems that will perform a function satisfactorily, may be used in the manufacture, processing, packing, and holding of a drug product.
If such equipment is so used, it shall be routinely calibrated, inspected, or checked according to a written program designed to assure proper performance. Written records of those calibration checks and inspections shall be maintained
Calibration, inspection, routine checks
Calibration records
Written program

6. US FDA 21 CFR Part 11 - Electronic Records, Electronic Signatures -
11/18/2018
US FDA 21 CFR Part 11 - Electronic Records, Electronic Signatures -
US FDA
11.10 (a): Computer systems should be validated to ensure accuracy, reliability and consistent intended performance
Part 11 Guidance Scope and Applications, C1. We recommend that you base your approach on a justified and documented risk assessment and a determination of the potential of the system to affect product quality and safety, and record integrity.

7. FDA Warning Letters Calibration, checking Requirements
11/18/2018
FDA Warning Letters
Your firm failed to establish and maintain procedures to ensure that equipment is routinely calibrated, inspected, checked, and maintained (160)
Inspection and Testing of Manufacturing Equipment, xxx do not fully describe the requirements for equipment qualification, including environmental conditions for equipment operation. (164)
Calibration, checking
Requirements
Ref:

8. FDA Warning Letters IQ IQ/OQ OQ PQ
11/18/2018
FDA Warning Letters IQ
Manufacturing equipment used in the production are not labeled or identified in the batch record (112)
Lacks documentation of installation and operation qualification of equipment (160)
The Validation Master Plan does not contain an operational qualification for xxx (164)
There is no requirement for a Performance Qualification protocol (164)
IQ/OQ OQ PQ
Ref:

9. FDA Warning Letters Data transfer Security
11/18/2018
FDA Warning Letters
Data transfer of a (chromatographic) client server system not validated (W-029)
The functional, operational and security features of the data acquisition and storage … software have not been challenged or validated for accuracy or for reliability (W-029).
Data transfer
Security
Ref:

10. Configuration Testing
11/18/2018
FDA Warning Letters
The network ... module design limitations, which can only support up to four chromatographic acquisition systems, had up to five chromatographic systems connected. There was no validation showing this configuration to be acceptable (W-067).
Validation of the system did not include critical system tests such as volume, stress, performance, boundary, and compatibility (W-067)
Configuration Testing
Stress testing
Ref:

11. FDA Warning Letters Risk analysis Impact analysis
11/18/2018
FDA Warning Letters
For example, a formal risk analysis of the original system design and software changes to correct software bugs that caused incorrect functionality or performance problems, and to enhance the product, has not been documented. (W-146)
Although your software release notes briefly describe the nature of unresolved software bugs in a particular software version, they do not explain the impact of these software bugs on user needs and intended uses. (W-146)
Risk analysis
Impact analysis
Ref:

12. Validate Spreadsheets
11/18/2018
FDA Warning Letters
Failure to use fully validated computer spreadsheets to calculate analytical results for in-process and finished product testing [21 CFR (e)]. For example, the computer spreadsheets used to calculate analytical results for... have not been validated. (063)
QA/QC Spreadsheet Validation, is deficient in that only a small range of values are being used to challenge computerized spreadsheet mathematical calculations. (063)
Validate Spreadsheets
over wide range
Ref:

13. EU GMP Directive - Annex 11
11/18/2018
EU GMP Directive - Annex 11
Annex 11 to EU GMP Directive
Validation should be considered as part of the complete life cycle of a computer system. This cycle includes the stages of planning, specification, programming, testing, commissioning, documentation, operation, monitoring and modifying.
PIC/S Guide for Inspectors - Good Computer Practices
A lack of evidence for the quality assurance of the software development process, coupled with a lack of adequate validation evidence may very well be either a critical or a major deficiency.
PIC/S: Pharmaceutical Inspection Convention Scheme

14. Industry Recommendations
11/18/2018
Industry Recommendations
GAMP Guide for Validation of Automated Systems
Reference document for computer system validation
Referenced in FDA and PIC/S Guides
Uses V-lifecycle model, risk based approaches
Defines five software categories
Supplemented by Good Practices Guides for specific applications (lab systems, testing)
GAMP: Good Automated Manufacturing Practice Order from

15. CSV Lifecycle Models Validation/is not a one time event
11/18/2018
CSV Lifecycle Models
Validation/is not a one time event
Validation starts when you plan for and design a product (hardware, software) or a method.
Validation is finished when the product is retired and all data are successfully moved to a new system
Validation follows one of the lifecycle models DQ
URS PQ IQ FS OQ OQ DS IQ PQ
Build/Code
4Q Model
V-Model

16. Qualification/Validation Phases 4Q Model
11/18/2018
Qualification/Validation Phases 4Q Model
User requirement specifications
Functional specifications
Vendor qualification
Design Qualification
Installation Qualification
Operational Qualification
Performance Qualification
Check arrival as purchased
Check proper installation of hardware and software
Validation Report
Validation Plan
Test of functional specifications
Test of security functions
Test for user requirement specifications
Preventive maintenance
+ Change Control

17. Validation Master Plan - Purpose
11/18/2018
Validation Master Plan - Purpose
The key elements of a validation program should be clearly defined and documented in a validation master plan (EU GMP Annex 15)
Increases significantly efficiency and consistency of individual validation projects
Answers the inspector’s question: “What is your company’s approach towards validation?”
For:
corporate
site
department
specific systems
Framework for individual validation projects

18. Validation Master Plan - Contents
11/18/2018
Validation Master Plan - Contents
Scope, e.g., for all GxP regulated environments
Glossary, e.g., validation, qualification
Responsibilities
Steps/approaches for validation and testing, e.g., DQ, IQ, OQ, PQ
Criteria and examples for risk assessment
Release procedure, e.g., who has to approve
Discontinuance
Contents of validation report and other documents
Consistency
Efficiency
For audits

19. Validation Project Plan
11/18/2018
Validation Project Plan
Specifies strategy, approach, responsibilities, activities and deliverables of validation efforts
Includes - Scope, System description - Validation strategies - Responsibilities and team membership - Activities and deliverables - Supplier assessment - Risk assessment - Testing strategies, protocols, test procedures, acceptance criteria - DQ/IQ/OQ/PQ - Traceability matrix - Validation reporting - Record management

20. Design Qualification - Definition/Purpose
11/18/2018
Design Qualification - Definition/Purpose
Definition Design qualification (DQ) defines the functional and operational specifications of the instrument and details the conscious decisions in the selection of the supplier (EU Annex 15).
Purpose
Helps in all later phases, e.g., OQ and PQ testing
Answers the question: “What is the system doing and what are the system requirements and specifications?”
Ensures that the equipment was developed and manufactured in a quality environment?”

21. Design Qualification - Contents
11/18/2018
Design Qualification - Contents
Description of the application and intended use of the equipment
Description of the intended environment
User requirement specifications
Functional and performance specifications
Qualification of the vendor
Use vendor specifications for help

22. Leverage supplier tests
11/18/2018
Supplier Assessment
Purpose: determine the adequacy of the suppliers quality system
Types of assessment - Preliminary assessment (questionnaire, postal audit) - Detailed on-site audit (quality system, process, product)
Extent of the assessment depends on - criticality of the system, complexity - risk to data integrity associated with use of the system - ability to verify system functionality in the lab
Can reduce in-house testing through tests done by the supplier
Leverage supplier tests

23. Documenting Vendor Assessment
11/18/2018
Documenting Vendor Assessment #
Audit Item 3 2 1
N/A
Company profile
Organization
Software development
////more////
1 = Excellent (above average) 2 = Adequate (average)
3 = Poor (below average)
0 = Unsatisfactory
N/A = Not applicable

24. Installation Qualification - Definition - Purpose
11/18/2018
Installation Qualification - Definition - Purpose
Definition
Installation qualification establishes that the instrument is received as designed and specified, that it is properly installed in the selected environment, and that this environment is suitable for the operation and use of the instrument
Purpose
Make sure everything arrived as purchased
Make sure hardware and software is ‘properly’ installed and systems are properly configured
Make sure, components and systems are well documented

25. Installation Qualification - Steps
11/18/2018
Installation Qualification - Steps
Collect supplier’s environmental conditions, operating and working instructions and maintenance requirements
Compare systems, as received, with purchase order
Install of systems according to vendor specifications and engineering drawings
Verify proper software installation
Check documentation for accuracy and completeness
Document all components with asset and serial numbers
Assistance from Vendor

26. Operational Qualification - Definition - Purpose
11/18/2018
Operational Qualification - Definition - Purpose
Definition
Operational qualification (OQ) is the process of demonstrating that an instrument will function according to its operational specification in the selected environment
Purpose
Ensure that the equipment functions and performs as specified by the user across all operating conditions in the user’s environment

27. Operational Qualification - Steps
11/18/2018
Operational Qualification - Steps
Identify critical functions for the computer systems as defined in functional and user requirement specifications
Develop test cases for the functions and define acceptance criteria
Perform the tests
Evaluate results and compare with acceptance criteria
Document results
Assistance from Vendor
for OQ services
Hardware and software

28. 11/18/2018
Key Points for OQ Tests
Tests should be linked to user requirement and functional specifications (test traceability matrix)
Test cases should include normal and stress conditions
Tests should be quantifiable
Test cases should be designed for reuse
Extent of testing should be based on system complexity, impact on product quality and risk assessment
URS FS
Test

29. Traceability Matrix (here requirement specification vs. Test ID)
11/18/2018
Traceability Matrix (here requirement specification vs. Test ID)
Requirement Number
Requirement
Test ID
1.1
Example 1
4.1, 4.3
1.2
Example 2
1.3
Example 3
3.1
1.4
Example 4
3.3, 4.1
Please note: one requirement may need two tests, and one test ID may serve more than one requirements

30. Performance Qualification - Definition - Purpose
11/18/2018
Performance Qualification - Definition - Purpose
Definition
Performance Qualification (PQ) is the process of demonstrating that a computer system consistently performs according to a specification appropriate for its routine use
Purpose
Verify that the system and applications work as intended (before and during routine use)
Answers the question: “How can you be sure that the application works as intended day-by-day?”

31. Performance Qualification - Steps
11/18/2018
Performance Qualification - Steps
Regular disk maintenance
Regular virus checks
Regular system performance tests
Monitoring network traffic
Environmental monitoring
Change control procedures

32. 11/18/2018
Change Control
Main reasons for changes: hardware maintenance and repair and software upgrades
Changes must follow a documented change procedure
Procedure should require risk analysis and evaluation if the change may affect the computerized system's validation status
Document changes; what, why, who, how tested?

33. Example: Change Request and Control Form
11/18/2018
Example: Change Request and Control Form
Form ID
Date
Location
System ID
Description of change
Include reason for change
Impact of change
Evaluate impact on validation
Authorization to change
Name Signature Date
Approved by
Completed by
Implemented
Date of implementation
Comments
E.g., document observations, testing

34. Validation plan and validation report are most important
11/18/2018
Validation Report
Response to validation plan
validation approach
Describes application, use and environment of system
Summarizes test plan/acceptance criteria/results
Deviations from the plans
Authorizes use of system
Validation plan and validation report are most important

35. Qualification protocols, Vendor assessment Supporting material (plots)
11/18/2018
Documentation
Framework (corporate, site, department)
Master Plan
Project Plan
SOPs
For individual projects or processes
Written procedures
For individual products
Test procedures
Qualification protocols, Vendor assessment Supporting material (plots)
Test Records

36. 10 Worst Mistakes for Computer Validation
11/18/2018
10 Worst Mistakes for Computer Validation
Not understanding the business, the application and principles of computer validation
No validation policies and procedures
No or insufficient specifications
Not leveraging validation efforts and support from vendor
No or insufficient documentation of installed software and systems
No or Insufficient Testing and Documentation
Too much testing
No or Inadequate change control procedures
Spreadsheet applications not validated
Validation and testing not based on risk

37. Thank You I would like to thank All attendees for your attention
11/18/2018
Thank You
I would like to thank
All attendees for your attention
Dan Janal for moderating the session
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38. Laboratory Compliance Package
11/18/2018
Laboratory Compliance Package
With 30 SOPs and Laboratory Master Plan
Primer and Interactive audio seminar on laboratory compliance: requirements and strategies for implementation
30 SOPs for fast implementation
Multiple forms, templates and examples for consistent and effective implementation
Three gap analyses and master plan
10+ reference papers
FDA presentations
Analysts, IT and QA learn all about requirements and strategies And get SOPs and examples for easy implementation. More info:
Slide 38