Validation of Computer Systems

How can a pharmaceutical company prevent a complaint from the regulatory authorities The answer is to establish a quality system infrastructure to govern the acquisition and development of software and the acquisition and operation of hardware. Such a system should be implemented for both regulatory compliance and cost savings  

Chapter 4 contains an example validation policy, which describes a quaiity management system for the hardware and software components making up an IT system and its support environment. Chapter 2 also discusses IT strategies with due consideration to validation compliance. 

The term validation is often misunderstood by IT professionals not familiar with pharmaceutical industry terminology. Validation has often erroneously been seen as limited to a testing activity at the end of a software/ hardware project. Validation in the pharmaceutical industry is closely aligned to the principle of quality assurance, which is a holistic approach that aims to build quality attributes into a system rather than verifying quality through testing. A system that is built according to 

This chapter has reviewed the pharmaceutical industr5 s guidelines and regulations governing computer systems validation. Special emphasis has been placed on regulatory expectations and inspection practice. The aim has not been to present a detailed examination of inspection practice but to highlight key issues affecting the validation of IT and network applications. 

Wyrick, M. 1998. State of the Industry—Current Events. Presentation made at the ISPE Seminar Computer Systems for the New Millennium, in Orlando, Fla. on 18 November 1998. 

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Friedli D, Kappeler W, Zimmermann, S. Validation of computer system practical testing of a standard LIMS. Pharmaceut Acta Helv 1998 72 343-8. 

Qualification of equipment and validation of computer systems are not one-time events. They start with the definition of the product or project and setting user requirement specifications and cover the vendor selection process, installation, initial operation, ongoing use, and change control. 

The process for implementation and prospective validation of computer systems outlined in Figure 3 depicts the system application activities within each life-cycle phase and identifies key issues and considerations for each step. The process includes for evaluation of both the computer system product and the system supplier s working methods. The same life-cycle approach may be applied to validate the associated control and monitoring instrumentation [9]. 

The validation of computer systems is an exercise in project management. The fact that computers are involved does not mean that the approach will be significantly different. It does mean that the responsible users will be the focal point of computer systems validation they will have to assume the responsibility for validation of the computer systems they use just as they are responsible for all other compliance aspects of their operation. MIS will play a key role since their computer expertise and interface with the suppliers is required throughout the process. 

In common with all FDA-regulated products, quality is built into a computer system during its conceptualization, development, and operational life. The validation of computer systems is an ongoing process that is integrated into the entire SLC. 

The validation of computer systems performing regulated operations provides... 

Many groups, both within and outside the organization, support the validation of computer systems. It is the responsibility of Executive Management to provide adequate resources to support the achievement of compliance in the computer systems validation... 

After visiting and inspecting the supplier, the information obtained is analyzed against the acceptance criteria, current company requirements for the validation of computer systems, and the regulatory expectations for computing environments. A report is produced that documents the audit process, provides information on the current state of validation of the supplier and what may be needed for compliance and, based on the audit findings, provides a recommendation on whether the supplier can be used. 

The GMP regulations have been in existence since 1963. The current regulations are from 1978 (43 FR 45077), and amended in 1995 (60 FR 4091). The proposed GMP regulation from 1996, includes Section 211.220(a) that would require the validation of computer systems performing manufacturing-regulated operations. In addition to section 211.220(a), several other sections apply to computer systems and to responsible individuals. 

These revised regulations require the validation of computer systems. Systems covered by device GMP regulations include any system that directly or indirectly impacts the safety, effectiveness, or quality of materials, components, or the finished device. 

SLC processes and the identification of problems relating to the validation of computer systems. 

Validation of computer systems must be performed by qualified individuals and must... 

Validation of computer systems—The role of QA is of particular importance with respect to complying with Part 11, related to electronic records and computer validation. Clinical QA must ensure that any computerized system associated with a study is adequately validated and that the documentation for that validation is concise, complete, and available for audit. Clinical QA must provide the appropriate guidance to both the validation and information technology groups to ensure that clinical studies are not invalidated because of inadequately validated software or hardware. 

Design and qualification of critical support utilities Validation of computer systems, methods, manufacturing, and cleaning processes Labeling controls... 

PMA (1986), Validation Concepts for Computer Systems used in the Manufacture of Drug Products, In PMA Proceedings Concepts and Principles for the Validation of Computer Systems Used in the Manufacture and Control of Drug Products, Pharmaceutical Technology (May) 24-34. 

U.K. GAMP Forum, Supplier Guide for Validation of Computer Systems in Pharmaceutical Manufacture, Third Edition — GAMP 3, 1998, International Society for Pharmaceutical Engineers, The Hague. 

From the outset the aim must be to make validation as cost-effective as practicable. Several pharmaceutical companies who rushed into the validation of computer systems in the late 1980s and early 1990s discovered to their own cost that inefficient validation programs are hugely expensive, involving much more work than is really necessary. 

The inspector will normally write back to the pharmaceutical or healthcare company after the inspection to confirm significant findings (positive and negative). The letter can take many weeks to arrive. Observations concerning the validation of computer systems might be logged as specific items or incorporated within the text of the system s associated equipment/process. 

An adaptation of SETs CMM for application to the validation of computer systems is shown in Ligure 17.1. This is not a definitive adaptation and is based on the principles of CMM. An additional sixth level (0) has been added to deal with organizations that have not yet embarked on any validation capability. 

The validation of computer systems has been a topical issue for over a decade, and for many companies it is a routine topic for regulatory inspections. The importance of computer systems validation is set to continue with regulatory interest in the role of new technology and ever more pervasive use of computer systems to support the development, manufacture, and distribution of pharmaceutical and healthcare products. ... 

Successful validation of computer systems cannot be built in as an afterthought validation planning should commence as soon as possible after the requirement to validate the application has been determined. Retrospective validation is far more expensive and resource intensive than prospective validation, with no guarantee that regulatory expectations can be satisfied at the end of it. 

The validation of computer systems in the U.S. FDA-regulated environment is an ongoing process that is integrated with the entire System Life Cycle (SLC). Quality to a software system is introduced by following the system life cycle and following the key validation elements. 

The validation of analytical methods is a well-known problem in the analytical community [1], The international guidance for equipment qualification (EQ) of analytical instruments and their validation is in the development stage [2-4], At this time validation of computer systems for analytical instruments is less elaborated [5-7], The term computer system comprises computer hardware, peripherals, and software that includes application programs and operating environments (MS-DOS, MS-Windows and others) [5, 6], Since programs, software and the whole computer system are elements of the instrument used by the analyst according to the analytical method, successful validation of the method as a black box [8] means successful validation of the instrument, computer system, software and programs. On the other hand, the same instrument may also be calibrated and validated as a smaller (in-... 

This first article describes the validation and qualification of computer systems such as those for instrument control and data evaluation during development. Development validation of computer systems purchased from a vendor typically is done at the vendor s site, and even though most computer systems and software in analytical laboratories are purchased from vendors it was felt that such an article makes sense for users of such systems for two reasons ... 

Since 1982, a number of guidelines applicable to information technology (IT) and network applications have appeared for the validation of computer systems. Between 1995 and 1998, five comprehensive regulations and guidelines were published. It is therefore timely to compare these guidelines in regard to their scope and contents. 

Table 3.1. Regulations and Guidelines for the Validation of Computer Systems (1982-1998) ... 

Between 1984 and 1995, 163 Form 483s regarding the validation of computer systems were submitted to pharmaceutical companies. These... 

Table 3.7. Warning Letter from the Validation of Computer Systems for the Manufacture of Conventional Drugs ...

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