Computer System Validation in Pharmaceuticals

Validation is a critical tool to assure the quality of computer system performance. Computer system software validation increases the reliability of systems, resulting in fewer errors and less risk to process and data integrity. Computer system validation also reduces long-term system and project costs by minimizing the cost of maintenance and rework.

Validation of HPLC system is most critical and important because all regulatory authorities focus on this instrument and different data integrity issues are found during FDA inspections. Therefore, HPLC is taken as an example system for validation. Computer system validation protocol can be written in following steps.

1. User Requirement Specification: URS for HPLC system is prepared to describe the critical functionalities those are required for our analysis. Following point should be considered during preparation of user requirement specification for an HPLC system.

• The system should provide the capability of creating and updating method (include the requirements of injection volume, flow rate, runtime, column temperature, wavelength etc).
• The system should provide the capability of creating and updating sequence (include different requirements related to the injector, selection of vials, sequence copy and paste etc).
• The system should provide the capability of run full sequence or partial sequence of injections.
• The system should have provision for printing the report with the facility to select different print layout & command of the printer on different printers (include the requirements to change the print layout and print different parameters as theoretical plates, tailing factor and resolution etc).
• The system should capable to run single injection without preparing sequence.
• The system should capable to control the user access rights.
• The system should have an audit trail and electronic signature features to comply the 21CFR requirements.

Other requirements should be added as per the need for the company or quality control department.

2. Design Qualification: Design qualification ensures that the purchased computer system is according to our user requirement specification and it is capable to run the instrument that will be connected to it. Inspect Computer hardware like CPU, connections, power supply, On/Off switches etc.

A. Operating System Configuration: Under this system checkup, check actual system configuration with minimum requirements, e.g. Operating system, Processor, Hard disk memory, RAM etc.

B. Workstation Configuration: Under this checkup, check actual workstation configuration with recommended PC configuration. Record instrument details like instrument name, model number, Serial number, Software version, Instrument number (ID) etc.

3. Installation Qualification: During installation qualification following steps should be followed.

• Compare the computer system and its components with the purchase order.
• Check all documents as manuals, safety and validation certificates, maintenance instructions etc.
• Check the system for any damage during transit.
• Install the system by connecting its components.
• Switch on the system and ensure that all parts and components show power and perform electronic self-test.
• Now install the software as per manufacturer’s instructions.
• Ensure the correct software installed.
• Configure printer and other equipment modules.
• Note down all hardware and software installed on a computer with description.
• List all manuals and SOPs related to the equipment.
• Prepare an installation report should be prepared to define all serial and revision number of the hardware and software.
• The report should include the size of hard disk and RAM, version of operating software, monitor serial number, printer serial number, manufacturer, connection network type etc.

4. Operational Qualification: Computer system validation creates confusion for many pharmaceutical professionals because there are two things one is computer and other the instrument software. We should qualify operation of both separately.

A. Computer System Qualification

B. Software Qualification

A. Computer System Qualification: During validating of computer system perform the inspection of following points:

• Computer boot up check
• Date and time check
• Hard disk check
• Print drive check
• Network connection test
• Software version check
• Program alteration check

B. Software Qualification:

I) Workstation Software (access control, password policies and audit trail):

• User Authentication and access control check 
• Password log management function check 
• Number of password characters check
• Failed login detection
• User lockout function check
• Failed Login Log check 
• User access rights check 
• Password expiry alarm test 
• Software entry attempts option, availability and cross checkup
• Password expiry availability check
• System policy function check
• Audit trail check

II) Application Software Functionality:

• Method preparation check
• Method edit / delete control check
• Operation qualification check
• Post analysis process / reprocess check (integration, report preparation etc).
• Operation wise, checkpoints to be performed can be different for different software and instruments. In addition to above checkpoints, other essential checkpoints can be performed as per functionality and applicability of the software.

A separate checklist should be prepared for the testing of the software that should contain the functionality of the software, specification and observation.

Note: When computers are connected by means of local area network (LAN) it should be included in operational qualification. Correct communication between the computer and connected device should be verified. Data should be input at one part of the local area network and output data at another end should be compared. For example, if data of HPLC is stored on the server then chromatograms and reports should be compared after printed on the computer system and on the server after storage and retrieval of data files.

5. Backup and Restore: Backup of the analysis data should be taken after printing the reports and chromatograms. After backup data file should be deleted from the computer system (including recycle bin). Deleted data should be restored from backup file and print of reports and chromatograms should be compared with the original prints taken initially.

6. Validation Report: Computer system validation report should contain all observations. The data, screenshots and prints should be maintained. All deficiencies and corrective actions should be documented in the report.

7. Training:

Training program gives direction for execution and documentation of validation activity performed for the computer system. Training should be provided to all personnel involved in operating the computer system and software. Proper training record with attendance should be maintained.

8. Conclusion:

A final conclusion report should be prepared to indicate that all steps of computer system validation are followed and all functions of the installed software are working satisfactorily.

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