Computer validation

This article defines the criteria and processes for computer validation. Computer validation applies to all systems, including electronic capture systems in both the laboratory (scientific instrumentation) and field settings. Any system producing electronic records and documents, which regulators in the evaluation of product registration applications will use, needs to be validated. 

Computer validation establishes documented evidence to show that the computerized system will consistently function and meet its predetermined specification and quality attributes with a high degree of assurance. Some of the parameters tested in the validation process include the following ... 

Water system Cleaning practices Computer validation Process validation Test methods validation Sterilization procedures Stability evaluation... 

Madnia, C.K., S.H. Frankel, and P. Givi. 1992. Reactant conversion in homogeneous turbulence Mathematical modeling, computational validations and practical applications. Theoretical Computational Fluid Dynamics 4 79-93. 

Before a clinical trial starts, the use of technical aids such as IVRT, remote data entry and electronic diaries has to be considered. In Section 7.5.3.3, mention will be made of the use of electronic tracking system that provide status and monitoring reports. All these systems utilise computer systems that must be validated. Double and McKendry described computer validation as the process which documents that a computer system reproducibly performs the functions it was designed to do. The document Guidance for Industry - Computerised Systems used in Clinical Trials published by the FDA in 1999 gives clear recommendations of what is required (also see Section 7.5.4.1). 

Double ME, McKendry M. Computer Validation Compliance. Buffalo Grove, IL Interpharm, 1994. 

Figarole PL. Computer software validation techniques. DIA Conference on Computer Validation, Jan. 21-23, 1985. 

Stokes, T. et al.. Good Computer Validation Practices Common Sense Implementation, Interpharm Press, Inc., Buffalo Grove, IL, 1994. 

Proper functioning and performance of equipment and computer systems play a major role in obtaining consistency, reliability, and accuracy of analytical data. Therefore, equipment qualification (EQ) and computer system validation (CSV) should be part of any good analytical practice. It is also requested by FDA regulations through the overall requirement that equipment must be suitable for its intended use. While in the past, equipment qualification and computer validation focused on equipment hardware and stand-alone computer systems, recently the focus has been on network infrastructure, networked systems, and on the security, authenticity, and integrity of data acquired and evaluated by computer systems. 

The Good Automated Manufacturing Practices (GAMP) Forum has developed guidelines for computer validation [5] and a draft guidance on quality assurance of information technology (IT) infrastructure [6]. 

Equipment and computer validation master plans should include the following ... 

Verify correct functioning of the application software. Apply common computer validation practices. 

New to the industry is the requirement that all electronically kept records be validated in accordance with the CFR (Title 21, Volume 1, part 11 revised April 1, 2003 requirement. This is particularly true of instances in which the systems are custom-designed and, furthermore, where computer-controlled automated processes are used. There remain many misconceptions about makes up computer validation. The CFR guideline as listed below should be well understood ... 

To understand fully the importance of computer validation, one must realize that computers can perform the functions humans used to. Instructions such as SOPs are needed to instruct humans as to what functions to perform... 

The establishment stage includes verification, qualification, and individual validation, including process validation, computer validation, method validation, and cleaning validation. These establishment stage steps shall satisfy the principal requirements in Table 6. 

The overall concept of all of the following tools is that of risk analysis or risk assessment. Risk analysis helps to decide whether an aspect is GMP-critical or not. The risk analysis can be performed in a formal or more informal way. Following are two popular and import types of risk analysis. Another method, the fault tree analysis (FTA), has recently been used in the area of computer validation. This method is not described here, as it is a complex form of risk analysis. 

The pharmaceutical manufacturer must establish effective policies and plans for regulatory compliance and validation to enable individuals to clearly understand the company commitment and requirements. Computer validation planning should ensure an appropriate training program, preparation of validation guidelines and procedures, system GMP compliance risk and criticality assessment, a documented validation strategy and rationale, clearly defined quality-related critical parameters and data for the manufacturing process. 

The FDA has stated that it expects process, packaging, cleaning, and analytical and related computer validation studies to have been conducted, reviewed, and approved for both drug dosage forms and the bulk pharmaceutical... 

Audit Report. A report of an independent audit of the computer validation process by an internal auditor (i.e. Quality Assurance) should be included with the summary report to management. The audit should compare the SOP and the initial parts of the protocol (what the system should do) with the test plan results (what the system actually does) and the summary report conclusions. 

The control system of the freeze-drying unit provides control, monitoring and documentation of the process. Such a system must be reliable and comply with GM P and GAMP (Good Automation Manufacturing Practice) demands with respect to computer validation. It should be SCADA (Supervisory Control and Data Acquisition) compatible. A possible hardware architecture is shown in Figure 2.55.1. 

This book, relevant to FDA-regulated operations, provides practical information to enable compliance with computer systems validation requirements, while highlighting and efficiently integrating the Part 11 requirements into the computer validation program. The ideas presented in this book are based on many years of experience in the United States Department of Defense and FDA-regulated industries in various computer systems development, maintenance, and quality functions. 

Chapter 6 suggests an organization structure supporting the computer validation program. 

Chapter 9 discusses the subject of inspections and testing as part of the computer validation process. 

Computer systems shall be validated. The computer validation must ensure accuracy, reliability, consistent intended performance, and the ability to discern invalid or altered records. 

R.R.Herr and M.L.Wyrick, A Globally Harmonized Glossary of Terms for Communicating Computer Validation Key Practices, PDA Journal of Pharmaceutical Science and Technology, March/April 1999. 

During the implementation or update process, the introduction of a computer validation management cycle will provide a top-down approach to integrate computer systems validation strategies in order to support the project. Figure 5-1 suggests a computer validation management cycle. 

As with any process, an improvement mechanism is required in order to enhance the computer validation management cycle. The improvement mechanism will be identified based on experience in using the SLC, validation practices, and the analysis of software metrics. The following sections describe the overall scope of each document or activity. Detailed description of each activity can be found in other chapter of this book. 

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