INTRODUCTION:

The computers are play a vital role in during a development and manufacturing of drug and the medial devices companies, this computer systems performed a major role to produce a reliability, security, consistency, accuracy of the data². The CSV is giving the fundamental advantage like is to be reduce the human errors. CSV is system consists Product strength, purity, Quality. The U.S Code of federal regulation is focused on (GMP) Good manufacturing practice was inspected by food and drug regulation authority (FDA)Annexure 11 is composed to European agency to explained CGMP for its medicinal products.^1-3

Regulatory background:

American code of federal regulation has following references, which related to the computer system validating process. This system is explained the regulatory viewpoint of computer system validation process^4-5.

a) Current good manufacturing practice for finished pharmaceuticals -21 CFR-part 211.68):

When the systems is automated, mechanical and electronic equipment or other types of equipment, including computer, or related system will be performed satisfied⁵, it may be used in the manufacturer, processing, packaging, and holding of a drug product when such equipment is so used, it shall be routinely calibrated, inspected or checked according to a written program. It is designed to be assured the proper performance. Written records and calibrated substance and inspected material should be maintained⁶.

b) Good manufacturing practice for medical devices -21 CFR-part 820):

The mechanical, automa0074ed and electronic equipment placed in a quality assurance and a production area, it’s had capable for producing valid result. The computer is used at part of production and quality testing it’s should be admitted⁷. The variable computers software is used to validate so the adequate testing process are documented⁸.

c) Good laboratory practice for non –clinical laboratory studies -21 CFR-part 58):

A automatic data collection system involves to identifies a data input on accurate time of data entry⁹. If any changes are made in automated entries it should be indicates a reason for the changes, it’s helps to notify a date and responsible individual can be identified.

REQUIRMENT:

This requirement is allowing expose the scope of this project. In a CSV system the computers need a variable accession to validate the process¹⁰. The system validation requirements and its developments structures are discussed below through the flow chart Fig 1.

· Software, Hardware.

· Controlling system and Equipment.

· Operating system and documentation.

· Controlled process and Total computerized system

Lifecycle module:

This software is creating under the lifecycle development bases (SDLC). It should be involved to validate the computer validation process¹¹. Therefore, this model is applied as computers to evaluate each step of validation process¹². In this development process the efficient documents which gets enabled. A brief overview of this model is given by “Augsburg et al. (1994).

V-Module:

The v-module is known as ‘Verification’ and ‘Validation’ module it is an SDLC module. The v-module is executing the process in sequential manner¹³. The v-module is getting an extension based on the association of testing phase for each corresponding development stage. This means that for every single phase is development cycle, it is directly associating with testing phase¹⁴. This is highly disciplined process development because the next phase starts only after completion of the previous phase¹⁵.

In this phase like design specification, code development and code testing are not necessary. This module comprises of user requirements specification (URS) that is, Design qualification (DQ), Installation qualification (IQ), Operational qualification (OP), Performance qualification (PQ)¹⁵

Fig 2: V model

Reason for failures of computer system validation:

Without adequate and planning and preparation, computer system validation can encounter several problems, eventually leading to failure of the process¹⁶. The problems are included.

a) Insufficient documents and planning.

b) Insufficient definition of constitutes in CSV.

c) Insufficient definition of expected results.

d) Insufficient specification of software.

e) Software does not meet is specification.

f) Inadequate source code for software.

Various validations planning for avoiding a failure in computer system validations:

Computer system validation begin at the beginning of the system designed .it begins and goes through a complete SDLC. Various stages in computer system validation as follows

Master validation plan:

· Identifies of the parties’ responsibility for different parts of program

· Report of the equipment, and assay to be validated

· Determination acceptance of criteria for each system, process to be validated.

· Defining all SOP’s.

User Requirement Specification:

The user requirement specification is elaborately explained it status. Then the user what they do it. Its traits to having the detail about then on-functional requirement and restraints¹⁷.

The following criteria should be considered.

· Operation data is required.

· Programming standards and test procedure are developed.

· Integral groups are assigned project responsibility/ scheduled.

· System aces security.

· Data handling and reporting.

· Supplier supporting documentation and testing.

· Utilization of Standard operating procedure (SOP’s)¹⁸.

Design Qualification:

DQ is made both hardware as well as software.¹⁹ The hardware portion of the system description is prepared in text and chart formats. These documents provide signal, data, and process flow details. Some are hardware components

· Controller.

· Peripheral device.

· Networking modules and cabling

· Input and Output modules.

· Power requirements.

· Enclosures etc.

For software the DQ is assigned as

· Operating system software.

· Configuration system software.

· Application specification system software.

Installation Qualification:

IQ confirmed the computer system after received it designed and specified software, that is properly installed in the selected computerised system^20-24. This is suitable for the selected environment and attached with this operation and use of these instruments.

A manufacture’s recommendation for installation is requires and then checking for fulfilments of the manufacture requirements before installation procedure is stated.

Before Installation:

· Electricity.

· Water and gases.

· Humidity and temperature.

· Vibration level and Dust level.

· SOP’S.

· Operating manual, logbooks and software.

· Grounding, termination and tagging.

· Control cabinets and environmental condition.

· Purchase order.

· Specification

· Manuals.

· Spare part lists.

Operational Qualification:

OP in each protocol has met the IQ phase, OP is involved to check the equipment performance and it consists with user requirements specification and within a manufacturing specific range²⁵.

In the OQ phase, all test phase is tested individually, and their performance are documented²⁶.

This is the precheck process involved in this technical acceptance for the equipment and its facility, it can be performed only after the installation of IQ has successful.

· Temperature controls and fluctuations.

· Pressure / vacuums controlling system.

· CO2 controlling system.

· Display unit and signalling led.

· Fan and its speed controllers.

· Card reader and access control.

· Overheating and low temperature protecting systems and access.

· Motors and air flap controllers.

Performance Qualification:

PQ process is the final stage in equipment quality checking process and these stags itself to verify the documenting on a equipment working and its reproducibly within a specified working range²⁷.

According to the user needs the complexity of the system, performance qualification can be combined by installation qualification or operational qualification²⁸. Due to this qualification the data should be prepared before the equipment test qualification is running. Every equipment is tested individually and checks according to the tested plan based on the process description^29-30.

· Running checks.

· Software installation verification.

· Backups and restoration.

· Alarm, event, measuring and handling.

· Data records and reports.

· Control and monitoring loop operation.

· Power loss and recovery.

· System access security.

CONCLUSION:

Computer system validation in a pharmaceutical industry play a successful role in both quality management or quality assurance system, a formal system Development life cycle (SDLC) and qualification task performed throughout the SDLC. The CSV fulfil the all requirements and user expectation. The V model of SDLC and the requirements of computer system validation is clearly elaborated in this CSV system. In this system the methodologies of the required specification and test protocols are written, and its approval process is explained and then the validation methodology also be included²⁸. In this system specially included the reason for failure in CSV system and how it’s should be solved during the CSV in industries are also be given its is very helpful to gain a elaborate knowledge about the CSV computer system validation.

REFERENCE:

1. CFR, 21 CFR, Part 211: Current Good Manufacturing Practice for Finished Pharmaceuticals, sections 21 I .22: Proposed Rules, vol. 61. Federal Register, pp., 1996; 20104-20115.

2. Potdar M.A, cGMP for Pharmaceuticals, Pharmaceutical Validation, 3rd edition, Nirali Prakashan, Pune, 437 – 450.

3. Guidelines for Process Validation of Pharmaceutical Dosage Forms. Saudi Food and Drug Authority, Kingdom of Saudi Arabia, 2010.

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9. Nash RA, Wachter AH. In Pharmaceutical Process Validation. Third Edition; Revised and Expanded. Marcel Dekker Inc., New York. 1993.

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11. Loftus BT. The Regulatory Basis for Process Validation. Pharmaceutical Process Validation. Vol. 23, Marcel Dekker, New York. 1984.

12. Shoaib Alam Md. Pharmaceutical Process Validation: An Overview. Journal of Advanced Pharmacy Education and Research. 2 (4); 2012: 185-200.

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17. Sharon Strause ―Computer System Validation—Definition and Requirements‖ Originally published in the spring 2009 issue of Journal of Validation Technology, pp-1-5.

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19. Computer systems validation: quality assurance, risk management, and regulatory compliance for the pharmaceutical and healthcare industry GAS Wingate Wingate, G.A.S. (2004), 'computer systems validation: quality assurance, risk management, and regulatory compliance for the pharmaceutical and healthcare industry', Interpharm press.

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21. Validation of Solid Dosage Forms the FDA view, 1989; 15(6-7): 1119-1133.

22. World health organization. Guidelines on the validation of manufacturing process for pharmaceutical products. Geneva.1993

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24. Patel RC, Bhuva CK, Singh RP, Dadhich A, Sharma A. Pharmaceutical Process Validation, Pharmatutor – ART – 1053.

25. WHO Expert Committee on Specifications for Pharmaceutical Preparations. WHO technical report, series no. 863 – 34th report, Annex 6 – GMP: Guidelines on the validation of manufacturing processes.

26. FDA Guidance Update: process Validation: General Principles and Practices; version 01; 2009.

27. Guidance for Industry on general principles and practices of process validation; US Department of Health and Human Services, Food and Drug Administration. 2011.

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Received on 12.02.2020 Modified on 08.04.2020

Research J. Pharm. and Tech. 2020; 13(11):5591-5594.

DOI: 10.5958/0974-360X.2020.00975.0