computer system validation

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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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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.

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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

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Cont…

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2. Guidelines to Overlook

21 CFR Part 820 General Principles of Software Validation

21 CFR Part 11Electronic records and Electronic Signatures

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21 CFR Part 820General 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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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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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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This includes,

I. Software Engineering

II. Hardware Development

III. Environmental concern

IV. Programming requirements

V. Programming tools

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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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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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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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Programming requirements

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.

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Programming tools

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.

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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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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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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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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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Cont…

Documentation of Validation Activity

Validation plan – Strategic document Validation procedure – Detailed steps Validation report – Detailed results

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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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Cont…

Static Verification Techniques• Static analyses • Technical reviews

Extent of Validation

Depends on:

• Risk with the system• System’s Complexity

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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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6. Validation of E-Spread Sheets

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

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Cont…

History of Electronic Spread Sheet

ELECTRONICSPREADSHEET

YEAR OF DEBUT

LAUNCHER

VisiCalc 1978 Harvard

Business School

Lotus 1-2-3 1983 IBM

Excel 1984MicrosoftCorporatio

n

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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

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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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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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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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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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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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