This document outlines the importance of computer system validation (CSV) in the pharmaceutical industry, emphasizing the need for proper guidelines and methodologies to ensure compliance with regulatory requirements. It covers aspects of software and hardware validation, management information systems, and the reconciliation of operational needs with technology. The summary also highlights the specific principles for validating electronic spreadsheets and the significance of documentation in the validation process.

1. 1

2. Content
1. Introduction
2. Guidelines to overlook
3. Defining computer system needs
4. Management Information System(MIS) &
responsibilities
5. Key principles of validating & recordkeeping
computer system.
6. Validation of Electronic Spread Sheets
7. Summery of key issue of Computer Systems
8. Bibliography
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3. 1. Introduction
 What is computer & its need in Pharmaceutical
industry…???
 Pharmaceutical product research, development, manufacturing
& distribution require considerable investment in both time &
money. That’s why computerization has become key to
improving operational efficiency.
 The main OBJECTIVE of this CSV is to examine computer
system qualification as required for validation programs in the
regulated pharma industry, providing guidance & reference on
regulatory requirements, validation methodologies &
Documentation.
3

4. Cont…
FDA, by way of its Modernization Act of 1997, has
indicated its intention to achieve the following goals by
2002:
• Official submissions received and archived electronically
• Electronic submissions and reviews accessed from the
reviewer’s desktop computers
• Standardized analytical tools
• Publicly releasable materials available on the Internet
4

5. Cont…
Data &
information
Management
systems
Problem
Solving
applications
Communication
aids
Laboratory
automation
Process
control
Clinical trials
COMPUTER APPLICATIONS IN
PHARMACEUTICAL TECHNOLOGY
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6. 2. Guidelines to Overlook
 21 CFR Part 820
General Principles of Software Validation
 21 CFR Part 11
Electronic records and Electronic
Signatures
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7. 21 CFR Part 820
General Principles of Software Validation
Applicable to the validation of software
which are:
• Used as a component, part or accessory
of medical device
• Which is itself a medical device
• Used in the production of device
• Used in the implementation of device
manufacturer’s quality system
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8. 21 CFR Part 11:
Electronic Records & Electronic Signatures
(Guidance Documents for Industry)
• It was issued in March 1997.
• It allows us to use electronic records and electronic
signatures in place of paper records and hand-written
signatures.
• Revised in August 2003.
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9. 3. Define computer system needs
 Validation of any system operation starts with a
statement of what you need to accomplish. Express in
your own terms.
 For example, a large ph’ceutical manufacturing firm
need to maintain an online warehouse inventory. If the
inventory is inaccurate & out of date, or the information
faulty, there are some regulatory risks such that
accountability errors may result. But there are also some
business risk too. Raw materials may not be ordered on
time, accounting will not reflect actual usage, and
materials may sit unfound & unused.
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10. Cont…
 This includes,
I. Software Engineering
II. Hardware Development
III. Environmental concern
IV. Programming requirements
V. Programming tools
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11. Software Engineering
 Some substantive & prescriptive facts abut
software engineering have been learned in last 40
years. One of them is that early mistakes so called
designed & specification mistakes, take more time
& money to fix than later mistakes – such as
implementation, coding & documentation mistakes.
 During this stage, it is possible to specify the
hardware. For starters, it must run the software you
have just specified.
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12. Hardware Development
 In this case usually determine what size hardware
you need to buy. Above a certain price range, you
will find that the hardware manufacturer will be
happy to assist you in specifying which hardware in
their time will meet your needs.
 What your hardware vendor may not understand is
what goes on in the factory.
 The company will have to evaluate hardware in
terms of environmental issues.
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13. Environmental concern
 Ph’ceutical manufacturing environments are known to be dusty,
full of vibrations, and supplied with unreliable electrical power.
Keyboards, disk drivers, printers, power suppliers and fans, all may
need to be stabilized against changes in voltage during the working.
 Hardware vendor will have to tell you whether & how the
operating system accomplishes this. You may also need to get the
same information from software suppliers of your major system
components.
 To specify what will happen to you if a fire destroy the computer.
In practice, this is rare. Damage from power supply & water is
more common. For this your hardware supplier, or representative
associates with this must provide adequate backup solution.
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14. Programming requirements
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 The system analyst must create a technical description of
what the programmers have to accomplish & how they
should go about doing it. This is a crucial step, because
typically an individual programmer is not going to know
enough abt the overall system to avoid incompatibilities.
 System analyst are responsible for specifying how the
chosen hardware & software will be used to implement the
specific task.
 As much as possible, programmer should use tools &
techniques that eliminate or minimize programming errors.

15. Programming tools
15
 The major software components you choose to buy are often
sold as software productivity tools. More important is their use
as reliability tools.
 Examples, includes compilers, which flag dead code; screen
interfaces with the ability to do range checks on fields; libraries
of well tested arithmetic functions. It may be seen that some of
these are programmer tools, some are application desire tools, &
some are system specification or component isolation tools.
 Eg. Some OS provide better support for software tools than
others. A notable Eg. is UNIX, developed at “Bell Lab” for
testing the viability of software tooling ideas. Today, it contains
to offer a rich set of programming tools.

16. 4. Management Information System(MIS)
 MIS function must specify the followings:
I. Access to the system will restricted to authorised persons.
II. Operator keying will be checked for erroneous inputs.
III. Review & approval by another person will be required
before the computer can go ahead & act on critical input.
IV. Computer will alert responsible person when it receives
questionable inputs.
V. Complete audit trail of all transactions & changes will be
kept & made available to authorized user for review.
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17. Cont…
 MIS function must decided what parts to buy and
what to build in house.
 In practise this is an enormously difficult task.
Fortunately, it isn’t critical to reliability because we
have stated what the system must do, in Computer
System Needs.
 If we have not done so, this may be the weak point
where all is lost & may never be made reliable
again.
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18. 5. Key principles of validating & recordkeeping
computer system.
• System Requirements Specifications
• Documentation of Validation Activity
• Dynamic Testing
• Static Verification Techniques
• Extent of Validation
• Independence of Review
• Revalidation
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19. Cont…
 System Requirements Specifications
• First establish documented end user (i.e., a
person regulated by FDA)
• Requirements/intended uses which is
extremely important for CSV.
• Computer system implements those needs
correctly.
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20. Cont…
 Documentation of Validation Activity
 Validation plan – Strategic document
 Validation procedure – Detailed steps
 Validation report – Detailed results
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21. Cont…
 Dynamic Testing
• Key testing consideration
Testing Condition
Normal
Stress
Actual Performance Testing
Simulation Tests
Live, User-Site Tests
• Software testing
Structural Testing (White Box Testing)
Functional Testing (Black Box Testing)
Program Build Testing – stepwise performance testing
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22. Cont…
 Static Verification Techniques
• Static analyses
• Technical reviews
 Extent of Validation
Depends on:
• Risk with the system
• System’s Complexity
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23. Cont…
 Independence of Review
• Third Party Assessment
• Assessment by any Person of the Organization other
than who built it
 Revalidation
• As per requirement of user
• By system up-gradation
• During routine servicing and maintenance
• Via network like internet
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24. 6. Validation of E-Spread Sheets
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 Application of Electronic Spreadsheets:
• 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

25. Cont…
25
 History of Electronic Spread Sheet
ELECTRONIC
SPREADSHEET
YEAR OF
DEBUT
LAUNCHER
VisiCalc 1978
Harvard
Business
School
Lotus 1-2-3 1983 IBM
Excel 1984
Microsoft
Corporation

26. Cont…
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 Steps for Electronic Spread Sheet Validation
• 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

27. 7. Summery of key issue of Computer Systems
 Validation of Hardware
 The suitability of the hardware for the function it is to perform must be
demonstrated by appropriate tests.
The following questions should be addressed:
1. Does the capacity of the hardware match its function ?
2. Have the operational limits of hardware been identified & taken into
consideration in setting up the production procedure ?
3. Do the test include the worst conditions which will be encountered ?
4. Will the documentation include a validation protocol and test results
which are specific and meaningful ?
5. Is there a system to assure revalidation when significant changes have
occurred ?
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28. Cont…
 Much of the hardware validation may be carried out bye the
manufacturer, but the ph’ceutical manufacturer is responsible
for assuring that the equipment is suitable.
 when validation data are produced by an outside firm, the
drug establishment must keep information (protocols &
results) which are sufficient to show that the validation was
adequate.
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29. Cont…
 Validation of Software
 This may consider the following points
1. Does the software accept all the variation that could appear
in the operation it controls ?
2. Have the validation tests been performed under the most
challenging conditions of the process speed, data volume, &
data frequency ?
3. Have the tests been repeated at least 3 times ?
4. Is there a system to trigger revalidation when
programs, process parameters, or data handling are changed
?
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30. Cont…
 Computerized operations
 Includes following:
1. Calculation against manual results.
2. Input records against sensor indicators.
3. Component quarantine against warehouse location
and status of required tests.
4. Timekeeping against a separate clock.
5. Automated cleaning in place against SOP, residue
tests, & the firm’s method of assuring adequacy.
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31. 8. Bibliography
1) “Computers in Pharmaceutical Technology”, Encyclopedia of
Pharmaceutical Technology, Volume 3
2) WHO Technical Report Series, No. 937, 2006. Annex 4. Appendix 5
3) Phan T.T. “Technical considerations for the validation of electronic spread
sheets”, Pharmaceutical Technology, January 2003
4) Budhihandojo R. et al, “The future state of computer validation”,
Pharmaceutical Technology, July 2001
5) Wingate G. “The future of Computer systems validation in Pharmaceutical
Industry”, Drug Manufacturing and Supply 2006
6) www.fda.gov
7) www.computersystemvalidation.com
8) www.21CFRconsulting.com
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