PHARMACEIJTICA

ACTA
HEWETIAE
ELSEVIER Pharmaceutics Acta Helvetiae 72 (1998) 317-325

Computer system validation:

An overview of official requirements and standards
Andreas Hoffmann a,*, Jacqueline IGihny-Simonius b, Marcel Plattner ‘,
Vanja Schmidli-Vckovski d, Christian Kronseder e
aInstitute for Hygiene and Applied Physiology, Applied Vision Research, ETH Zentrum, CH-8092 Zurich. Switzerland
b Peter Merian-Str.28, CH-4052 Basel, Switzerland
’ IKS, Erlachstr.8, CH-3000 Bern 9, Switzerland
d Baxter AG, Industriestr. 31, CH-8305 Dietlikon, Switzerland
’ Institute for Inorganic Chemistry, ETH Zentrum, CH-8092 Zurich, Switzerland

Received 14 May 1997; revised 21 August 1997; accepted 3 September 1997

Abstract

A brief overview of the relevant documents for companies in the pharmaceutical industry, which are to be taken into consideration to
fulfil computer system validation requirements, is presented. We concentrate on official requirements and valid standards in the USA,
European Community and Switzerland. There are basically three GMP-guidelines, their interpretations by the associations of interests like
APV and PDA as well as the GAMP Suppliers Guide. However, the three GMP-guidelines imply the same philosophy about computer
system validation. They describe more a what-to-do approach for validation, whereas the GAMP Suppliers Guide describes a how-to-do
validation. Nevertheless, they do not contain major discrepancies. 0 1998 Elsevier Science B.V.

Keywords: Computer systems; Validation; GMP; Quality assurance; Inspection

1. Introduction and a system is disclosed in Annex 11 (Computerised

The growing use of computerised systems in the phar-
maceutical industry in the last decades requires increasing
efforts in validating hardware and software. The validation
efforts should use underlying principles which are used for
validation of processes or analytical methods. Nowadays
official inspections in companies concentrate more and
more on validation of computerised systems due to GMP.
Several guides and interpretation of guides exist but there
is no detailed guide available which is valid for all coun-
tries.
Different definitions exist for the term computer sys-
tem. The European definition of a computerised system
* Corresponding author. Fax: +41-l-6231173;
hoffmann@iha.bepr.ethz.ch.
Systems) of the EC-GMP-Guidelines. (EC, 1989).
Computerised System: A system including the input of
data, electronic processing and the output of information to
be used either for reporting or automatic control.
System: Is used in the sense of a regulated pattern of
interacting activities and techniques which are united to
form an organised whole.
An American definition of a computerised system is
given in the PDA Technical Report No. 18 (PDA, 1995).
Here a computerised system is defined by a pure computer
system and the controlled function. The computer system
includes hardware and software. The controlled function
maybe composed of equipment to be controlled and oper-
e-mail: ating procedures that define the function of such equip-
ment, or it may be an operation which does not require

0031.6865/98/$19.00 0 1998 Elsevier Science B.V. All rights reserved.

PII SOO31-6865(97)00028-9
318 A. Hojjtkuuzn et al./ Pharmaceuticu Acta Helvetiae 72 (1998) 317-325

different steps of qualification which have to be taken into

account. Design qualification defines the quality parame-
ters required of the equipment and manufacturer. The
specification of the system will be defined. The installation
9
qualification should establish confidence that process
Computer System Controlled Function
equipment and ancillary systems are capable of consis-
tently operating within the specified limits and tolerances.
Fig. I. Computerised system.
It has to be proven that the intended equipment reaches a
standard which has been specified in the design specifica-
equipment other than hardware in the computer system. tion. The operational qualification should confirm that the
This computerised system definition is illustrated in Fig. I. equipment functions as specified and operates correctly.
Computerised systems or computer systems in Sections Last but not least the performance qualification has to
2-4 should be seen as computerised systems defined by confirm while using the system that the equipment consis-
PDA. Computer system validation therefore will mean the tently continues to perform as required.
validation of the pure computer system and its controlling Two different approaches to the validation of comput-
production process. erised systems have been introduced: a retrospective vali-
Computer validation in the pharmaceutical industry is a dation is required, if the system is already installed. This is
fairly new field. That is why it is very difficult to find a only applicable to older systems, which were set up before
comprehensive overview of the guidelines. The guidelines validation requirements had been defined. A prospective
are often under revision and many different guides exist. validation starts while designing a new system. Dannapel
Nevertheless, this paper tries to provide an overview of et al. (1995) state that nowadays validation goes hand-in-
guidelines and legal regulations concerning computer sys- hand with the system development. This leads to a close
tem validation in the pharmaceutical industry. The regula- connection between the validation and the developed sys-
tions presented concentrate on the European Community, tem and allows reasonable changes in the approaches to
USA and especially Switzerland, being part of Europe but validate new systems.
not of the European Community. The differences in the In order to manage the activities necessary to produce a
valid guidelines to be followed are presented. validated system it is recommended that suppliers follow a
formal quality management system. Today, there are a few
methodologies available for validating a computer system.
2. Overview of validation Historically, two models, the life-cycle model and the
V-model, have been developed to describe the validation
Validation is applied to many aspects of pharmaceutical procedure.
manufacture; examples include services, equipment, com-
puters, processes and cleaning. In each case the objective 2.1. Life-cycle model
is to produce documented evidence which provides a high
degree of assurance that all parts of the facility will Software development uses a life-cycle development
consistently work correctly when brought into use. One model. Each step in the software development process can
definition of validation is given by the FDA (FDA, 1987): be connected to a step in the computer validation. There-
fore, this model can be applied to computer system valida-
Validation is the establishing of documented evidence
tion to illustrate each step in the validation process. This
which provides a high degree of assurance that a specific
enables an efficient documentation of the development
process will consistently produce a product meeting its
process. A brief overview of the model is given by Augs-
pre-determined specifications and characteristics.
burg et al. (1994). The life-cycle model is described by
As stated above, validation is a required approach in the basic steps, which are illustrated in Fig. 2.
pharmaceutical industry to assure quality. Validation basi- Each step of this model is described as follows:
cally concerns all steps in the production process, which (1) Requirements and design: A new computerised sys-
could affect the final quality of the product. Therefore tem may replace an older pharmaceutical process or may
validation is an important contribution to quality assur- start a new process. The functional requirements are deter-
ance. mined. While the development life-cycle starts, the group
The American Parental Drug Association, PDA, re- of people, responsible for validation should be selected.
leased in October 1995 guidelines to validate computer-re- The responsibility of the Validation Committee is to define
lated systems (PDA, 1995). These guidelines deal with the validation plan, which outlines the tasks and deter-
 A. Hofmann et al. / Phamceutica Acta Helvetiae 72 (1998) 317-325 319

.O 0
Production Requirements
5 ) 1 ...‘...
and Maintanance ..-..., and Design

t
Validation
Testing
I

Installation :. Coding
Testing

Fig. 2. The life-cycle model.

mines the resources required for validation. The system tem design documents should be available for review and
specifications have to be defined. The detailed description updates.
of the final computerised system has to be documented. (4) Installation testing: The end user performs the sys-
During this phase the documents to be produced while tem’s task with his/her own data and procedures. System
validating are identified. This covers protocols and reports. failure leads to new documentation and re-design.
The system documentation might be updated due to valida- (5) Production maintenance: The system is released for
tion efforts. production. System changes (software or hardware) have
(2) Coding: At the beginning of this phase, the valida- to be documented and controlled in a predefined manner.
tion plan should be finished off. Information about the The first and second step can be linked to the earlier
validation test environment, assumptions, exclusions and mentioned design qualification, step three and four will be
limitations about the system as well as installation proce- validated in installation qualification and the task of per-
dures should be clarified. This phase covers the implemen- formance will be linked to step five of the above life-cycle
tation of software and construction of hardware. model.
(3) Testing: Th’1s complex phase can be divided into This life-cycle model is explicitly mentioned in the
several phases. All single modules whether they are hard- APV Guideline ‘Computerised Systems’ based on Annex
ware or software have to be tested. Afterwards an integra- 11 of the EC-GMP-Guidelines (APV, 1996), which will be
tion test has to be performed. While the developers con- discussed further in this paper.
duct unit, system and integration testing, the Validation
2.2. The V-model
Committee is in a position to define test cases and data
running the acceptance test. Several documents such as, The Forum for Good Automated Manufacturing Prac-
requirement documents, functional specification and sys- tice introduced guidelines (GAMP, 1996) for suppliers

Level I
User Requirement Specification . . . . . . . Automated Performance Qualification

1 Level 2 T
System Function Specification . . . . . . System Acceptance Testing

1 Level 3 T
Hardware Design Specification Hardware Acceptance Testing

1 Level 4 T
Software Design Specification Software Integration Testing
1
1 Level 5 T
Software Module Specification .-.-.--.-.---..-.-. Software Module Testing

1 T
I Code Modules

Fig. 3. The V-model: The left part of the V-model concerns on constructing the system whether the right part focuses each step of the system validation
process.
320 A. Hojinann et al./ Phamaceutica Acta Helvetiae 72 (1998)317-325

within the pharmaceutical manufacturing industries. A

1513I YIEEC
slightly different model is taken as basic orientation through Y 11356lEEC
the development of a computerised production process.
This V-model by Boehm (Boehm, 1979) is depicted in Fig. EC-GMP Guidelines
3. Each level of the V-model is semantically equivalent to
a step in the life-cycle model.
Annex 11:
<hidelines for Computerized
2.3. Quality assurance Systems

Validation is part of quality assurance. Miiller et al. Fig. 4. European community legislation.

(1996) describe quality assurance as an approach involving

all resources (manpower, machines, know-how, etc.) of a
company to produce a product of the quality required by
the customer/authority and considered as safe and effi-
cient by the authorities to the benefit of the employees, the
company and the patient. Quality assurance involves all
divisions of a firm and, to be successful, quality assurance
must be aware of the key problems in the manufacture of
drugs. Quality assurance must know what level of quality
has to be assured with the existing and steadily progressing
techniques. Science, development, research and regulatory
requirements are linked to each other, since development
will change the current state of the art and regulations will
and must alter accordingly. The development of quality
concerning aspects began with the quality control of a
product, where quality was analysed into the product.
Modem concepts include quality assurance and quality
management i.e. IS0 9000 (ISO, 1987).
guidelines for the validation of computerised systems. This
results in the legislation depicted in Fig. 4.
The development of these EC-GMP-guidelines was
closely related to the PIC-GMP-guidelines (PIG, 1989).
PIC is the Pharmaceutical Inspection Convention that was
founded in 1970 by EFTA-countries. Therefore the EC
document can be seen as an extended PIC-document.
Nevertheless it should be taken into consideration, that the
documents have different objectives. The main focus of
EC-GMP was the standardisation of GMP-regulations in
the EC-countries and to assure quality in the production
process of medicinal products. The PIC-GMP-guidelines
can be used as a standard for documentation for companies
which focus on GMP. Therefore PIC-GMP guarantees that
the administrative bodies of all PIC-members can perform
inspections using the same criteria.

3.1.2. Switzerland
3. Governmental regulations and guidelines The manufacturing and quality control of medicinal
products is regulated by the Cantons. Switzerland is di-
Regulation in this field is many fold and it is not always vided into 26 Cantons. These 26 Cantons have founded a
easy to have an overview of it, since its status in the legal concordat called Interkantonale Vereinbarung (IKV), from
hierarchy may spread from law to strong recommendation. where the Intercantonal Office for the Control of Medicines
A brief overview is presented for the EC, Switzerland and (Interkantonale Kontrollstelle fur Heilmittel) (IKS)
the USA. emerged. IKS, on behalf of the cantons, is mainly respon-
sible for the registration of medicinal products. In the field
3.1. Governmental regulations of GMP the IKS has issued manufacturing guidelines
(IKS, 1995) which adopt the guide to good manufacturing
3.1. I. European community practice issued by PIC (PIC, 1989) and also consider
The requirement to follow good manufacturing practice recommendations of the World Health Organisation (WHO,
in EC-countries is laid down in the EC directive 1992). European directives and guidelines but also intema-
75/319/EEC (EC, 1975). Differences concerning the con- tional regulations (e.g. WHO, European Pharmacopoeia)
tent and number of national GMP-guidelines in EC-coun- are considered in Swiss legislation and they are often
tries led to the publication of the EC directive accordingly adapted into Swiss law. These IKS-manufac-
91/356/EEC (EC, 1991) on the principles of good manu- turing guidelines are not applicable to the production of
facturing practice and the homogenous EC-GMP-guide- pharmaceutical goods in public or hospital pharmacies.
lines (EC, 1989) belong to it. Hence, these guidelines are The legislation in Switzerland is depicted in Fig. 5.
now mandatory for all EC-members. The main document Due to the very complex legal framework it is in the
of the EC-GMP-guidelines has been amended by several authority of the Cantons to issue manufacturing authorisa-
annexes, one of which is number 11 which provides tions whereas GMP-certificates for instance are issued by
 A. Hoffmann et al./Phamaceutica Acta Helvetiae 72 (1998) 317-325 321

products in the USA is the Technical Report No. 18

1 IKS-Manufacturing Guidelines
published by the Parenteral Drug Association (PDA, 1995).
I I
PIG-GMP Guidelines WHO-Guidelines 3.2. Non-governmental organisations

There are several non-governmental organisations

Annex 11:
Guidelines for Computerized (NGOS) in Europe and USA which interpret and comment
Systems
on guides and guidelines published by their national au-
thorities. A selection of these organisations is listed here.
Fig. 5. Swiss legislation.

3.2.1. APV
the IKS. GMP-matters are therefore a shared responsibility The International Association for Pharmaceutical Tech-
leading to several inspectorates, one at the IKS and the nology (Arbeitsgemeinschaft Pharmazeutische Verfahren-
others cantonal or regionally structured. In the near future stechnik, APV) is originally a German association. This
four regional areas will be constructed and IKS will use its organisation founded the board of Information Technology
position as co-ordinating institution. which discusses the problems and chances of modem
information technology. This specialist section published a
3.1.3. USA detailed interpretation of Annex 11 (APV, 1996).
Muller et al. (1996) state that the regulations and points
of view of the US regulatory authority Food and Drug 3.2.2. PDA
Administration (FDA) are certainly important for manufac- The Parenteral Drug Association (PDA) is an American
turers all over the world exporting into the USA. There- association which founded a committee Validation of
fore, an overview is presented how quality related FDA Computer Related Systems. This board assembled a guide-
regulations concerning the production of drugs are organ- line for the qualification of computer systems and com-
ised. The congress enacts the Food, Drug and Cosmetic puter related systems as a Technical Report (PDA, 19951,
Act and FDA’s existence is due to the mandate to approve which is now an important document for computer system
drugs based on the demonstration of safety, efficacy and validation in the USA.
quality. The legislation in the USA is depicted in Fig. 6.
The contents of the FDA-GMP-guidelines (FDA, 1987) 3.2.3. GAMP-Forum
is conceptionally comparable with the EC-/PIC-GMP- In 1990 an informal group, the UK Pharmaceutical
guidelines but there are differences in the content. For Industry Computer System Validation Forum (PICSVF)
example, the FDA-GMP-guidelines do not have a supple- was set up to establish a compendium concerning the
ment chapter explicitly about validation of computer sys- validation of automated systems in pharmaceutical manu-
tems whereas the EC-GMP-guidelines contain a special facture. In the following drafts and versions the EC-GMP
annex. On the other hand the FDA recently issued supple- Annex 11 and further comments of companies from all
mentary regulations concerning i.e. electronic signatures over Europe and the USA were incorporated. This led to
CFR (1995). version 2.0 of the GAMP Supplier Guide (GAMP, 1996)
Changes in the pharmaceutical field lead to a reaction which was published by the Good Automated Manufactur-
by the authorities. The guidelines should keep up with the ing Practice Forum in May 1996.
new trends in industry. Therefore, since 1987 the FDA-
GMP-guidelines have been frequently revised as so called
current GMP-guidelines, (cGMP) and the guide is still in
the revision process. Proposed changes have been already
published in the Federal Register, CFR. This Code of
Federal Regulations, CFR 210/211 (CFR, 19961, is on a
Code of Federal Regulations
higher legal level compared to the guidelines and guides
(ZICFR 210+2ll)
which have the status of recommendations, however, most
stringent recommendations.
The earliest document dealing with computer validation
was the Blue Book (FDA, 1983). It is usually applied as and other Guidelines
guidance for inspectors. The valid document for validation
in the computer-related environment for pharmaceutical Fig. 6. USA legislation.
322 A. Ho@zann et al. /Pharmaceutics
3.2.4. IS0
The International Standard Organisation (ISO) is a
world-wide association of national standard authorities of
about 100 countries. The purpose of this organisation is to
facilitate the international co-ordination and unification of
industrial standards. The IS0 9000-9004 standards (ISO,
1987) treat the implementation of a quality assurance
system in a company regardless of the industry branch.
These norms do not lay down the quality of a product, but
the norms document the ability of the company to produce
quality. This comes close to the validation paradigm in the
pharmaceutical industry.
3.3. Guides and guidelines
3.3.1. European Community
In order to harmonise the national GMP-guidelines of
the different countries in Europe, a Guide to Good Manu-
facturing Practice for Medicinal Products was established
by the member states of the European Community (EC,
1989). These rules guarantee that medicinal products are
produced and manufactured under the same conditions and
regulations in all member states. The central document has
been extended by several annexes concerning special top-
ics which have not been regarded so far or have to be
explained in greater detail.
In Annex 11 of the EC-GMP-guidelines (EC, 1989) the
Guideline for Computerised Systems, the principles of
GMP concerning equipment which involve computerised
systems are stated. These principles do not only cover
computerised systems in production facilities but also af-
fect computerised systems used in warehousing, data stor-
age, distribution and quality control. Summarising, it in-
cludes all computerised systems which have influence on
the quality of the intended product.
3.3.2. USA
First efforts to take the technological progress in the
computer sciences and related fields into account led to the
Blue Book (FDA, 1983). In the meantime the recommen-
dations and guidance laid down in this book are regarded
as outdated. Currently the FDA argues that sufficient
domestic and international guidelines are available to pro-
vide assistance to manufacturers for the validation of
software and computerised systems, e.g. ISO-9000-3 (ISO,
1987) Technical Report No. 18 (PDA, 199.5) which con-
tain computer validation guidance. FDA-guidelines con-
cerning computer system validation are still under revision.
3.3.3. GAMP supplier guide
The field of validation of automated systems in pharma-
ceutical manufacturing became of much greater impor-
Acta Helvetiae 72 (1998) 317-325
tance and the interpretation of regulatory guidance was
more demanding than in other conventional areas. In-
creased complexity of automated systems required better
communication, not only within the pharmaceutical indus-
try, but also with its suppliers. The GAMP Supplier Guide
is intended to clarify customer’s requirements, so that new
computer systems can be more easily and cost-effectively
validated. The guide should help suppliers to ensure that
systems are developed with built-in quality and provide
documentary evidence that their systems meet the agreed
specification. Sample procedures and forms are provided
in the guide, which enable suppliers to implement a suit-
able quality management system within their organisation
to meet the needs of the pharmaceutical manufacturing
industry.
In this sense the guide goes one step further than Annex
11 since it includes explicitly the suppliers in order to
establish a stringent quality assurance system.
4. Discussion
4.1. Importance of computer system validation
Today, computerised systems are used in nearly all
parts of the pharmaceutical company (production, adminis-
tration, accounting, etc.). Due to regulation-attached re-
quirements systems in production, controlling and distribu-
tion of manufacturing industry have to be validated.
From the quality assurance point of view systems can
be divided into two classes: systems, which are GMP
relevant and systems, which are not relevant according to
GMP. The classification of a system into one of those
classes gives also an indication about the efforts of valida-
tion. The systems which are classified as GMP relevant
systems require careful and regulation attached validation.
Nevertheless, systems which are not GMP relevant in the
first place should also be validated. The reason is that
validated systems reduce technical and functional risks
which lead to more reliable data. That is an important
factor for quality assurance.
The effort for validation of computer systems is deter-
mined mainly by the used software. The effort increases as
soon as the system has been adapted to customer demands.
Unchanged standard software requires reduced energy and
cost for validation. Especially small companies have to pay
attention to this before choosing a configurable software
package or even a custom built system. The co-operation
with commercial institutions who are specialised in com-
puter system validation might be especially helpful for
small companies. Nevertheless, this approach has to be
 A. Hojjkznn et al. / Phamaceutica
regarded with caution. The customer has to consider the
cost of this option.
For newly developed computer software, validation can
be seen as a concept of quality assurance in electronic data
processing. In most companies there is a parallel develop-
ment of quality assurance and information technology.
Quality assurance has been applied from production and
analytics, whereas information technology rather comes
more from the administrative parts. It can often be seen
that the information technology is not adequately covered
by quality assurance. In companies with long-time use of
computers, it also occurs that standards in quality assur-
ance are used but they are not carried through for all
computer applications. Therefore it can be said, that the
validation of computer systems is often not given the
importance it should be. Another problem is that docu-
ments which were required for validation frequently do not
exist and companies rely strongly on the competence of
their employees.
Many user systems have been installed before valida-
tion was required by law in Europe. Despite the non-paral-
lel development and validation, practice shows that most
of these systems perform their tasks reliably. Nevertheless,
these systems do not always fulfil the requirements of a
modem computer validation. The substitution of such ex-
isting software or hardware results often in big efforts even
if only a part is substituted. For every changed module a
validation is required. An overall retrospective validation
of the system will lead to the lawful acceptance of the
system as a validated system.
4.2. Guidelines
In the USA the FDA-cGMP-guidelines (CFR, 1996)
require a validation of computerised systems. The guid-
ance to performing this validation is still under develop-
ment, since computer validation is a new field in valida-
tion. The objective of transferring what is desirable in
theory must be applied in practice.
The EC directive (EC, 1991) and its corresponding
EC-GMP-guidelines (EC, 1989) as well as the PIC-guide-
lines (PIG, 1989) require also a validation of computerised
systems. Here, Annex 11 describes additional cornerstones
and points which have to be taken into consideration while
validating computerised systems. In brief it can be said
that the GMP-guidelines on Good Manufacturing Practice
for Medicinal Products are mandatory in the countries of
the European Union as well as in Switzerland.
There are basically two approaches to give guidelines
for validation. First is the description of a how-to-do
validation, while the second gives a guideline for what-to-
Acta Heluetiae 72 (1998) 317-325 323
do. However, there is no existence of an overall regulatory
guide for validation, that is why the interpretations by
non-governmental organisations are important.
In the USA the PDA Technical Report No. 18 (PDA,
1995) is the most essential document, whereas in Europe
the APV-guidelines (APV, 1996) reflect an important in-
terpretation of Annex 11. Both documents show what-to-do
to achieve the objectives of computer system validation in
detail. This what-to-do is accepted and seen as being
sufficient, especially by large companies. These companies
view the flexibility of this approach as an advantage.
The capacity of smaller companies demands a compre-
hensible description and guide about how-to-do validation.
The GAMP-guide (GAMP, 1996) takes this demand con-
cerning prospective validation into account. Nowadays, the
GAMP Supplier Guide is the most comprehensive and
most detailed guide for the qualification of all kinds of
computer systems and has considerable international sig-
nificance. The document can be designated broadly as a
general guide to achieve a validated computerised system
and should be regarded as a very important document.
The lack of governmental procedures in great detail can
also be seen as a chance. It allows flexibility to move
within the legal requirements. Standards set by customers
and suppliers of computer systems come closer to require-
ments in the real world than detailed regulations made by
authorities.
In the near future, the described standard documents
will receive more importance. The groups of interests
nowadays focus on standardisation guides for detailed
questions, i.e. electronic signature.
4.3. Aspects of inspections
The publication of the Blue Book (FDA, 1983) is the
only official document that contains guidance for inspec-
tors. However, the authorities provide support for inspec-
tors and the trend to harrnonise the level of inspections is
made by joint-inspections and discussions on conferences
like PIC (1996).
Neither the FDA nor another authority published a
checklist or a guidance for industry so far. Because the
topic of computer system validation is relatively new,
many aspects have not been fixed yet. The FDA an-
nounced a guide, which should be published in 1997 and
so did PIC. As declared, the PIC-guide will be an overall
document, covering all important papers published by
various non-governmental organisations. Switzerland will
deal without an own guideline but the authorities will
accept the international standard. In addition, there is the
intention to create a checklist for the industry.
324 A. H&inann et al. / Pharmaceutics Acta Helvetiae 72 (1998) 317-325

Currently the GAMP-guide and the publications from
PDA and APV represent the only sources for requirements
checked at an inspection, but there exists flexibility for
interpretations by inspectors. A validation extent of differ-
ent topics is given in the GAMP Supplier Guide, chapter
10: Validation Strategy for Different Types of Software
Products.
In the sense of documented evidence it is important to
complete the documentation for all steps of the life-cycle
model. Even during a retrospective validation this model
should be followed as far as possible. Particular critical
points in computer system validation and therefore possi-
ble starting-points for an inspection are the risk-analysis,
planning, the specifications, the security of access, the
security of data and the hole change control.
tion of all partners and the aim to have world-wide har-
monisation is a declared objective for the future intema-
tional work.
Acknowledgements
We thank Dr. Annette Beck-Sickinger, Dr. G. Imanidis
and Dr. S. Marrer for organising the seminar and for their
competent guidance. Our special thanks go to Dr. S.
Marrer, F. Hoffmann-La Roche AG Basel, for his useful
advice concerning the manuscript and for kindly reviewing
it.
References

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