Good

Computer
Validation
Practices
Common Sense Implementation

Teri Stokes
Ronald C. Branning
Kenneth G. Chapman
Heinrich J. Hambloch
Anthony J. Trill

Interpharm Press, Inc.

Buffalo Grove, IL
 Contents

Preface xi

1 Computer Validation Projects, Problems, and

and Solutions: An Introduction 1
Anthony J. Trill
Large Projects—Controversy and Disasters 1

Pharmaceuticals and Devices—Quality and

Safety Issues - 2

Computerized Systems—People and Procedures 3

Building Quality into Systems (SDLC and GSEP) 4

EC GMP Requirements and Personal Responsibilities 5

EC Rules and Guidance for Pharmaceutical

Manufacturers 6

Information Management Strategies 9

Conclusions 9

References 10
HI
iv Contents

2 International Regulations and Computer

Systems: GCP/GLP/GMP 11
Dr. Ten Stokes
GLP Computer Systems—UK, Japan, United States 12
Common Themes—GLP Computer Systems 16
GCP Computer Systems—Scandinavia, Australia,
EC, United States 16
Common Themes—GCP Computer Systems 24
GMP Computer Systems—Pilot and Production-
Specific Guidelines 24
Conclusion 31
References 31

3 The Role of Senior Management in

Computer Systems Validation 35
Dr. Ten Stokes
What Is the Validation Role of Senior Management? 36
What Should a Validation Policy Document Contain? 38
How Does One Implement Corporate Validation Policy? 42
How Do We Get from Corporate Policy to a Validated
System? 45
Conclusion 45
Reference 46

4 Documentation Practices and Principles 47

Kenneth G. Chapman
Validation Document Categories 48
Document Quality 50
 Contents v

Starting Principles 57
Actual Documents 59
What's Missing? 71
References 71

5 Validation Concepts and Key Terminology 75

Kenneth G. Chapman
Some Key Terms 76
Summary 89
References 89

6 Existing Computer Systems: A Practical

Approach to Retrospective Evaluation 93
Dr. Heinrich Hambloch
A Strategy for Retrospective Evaluation 94
The Phases of Retrospective Evaluation 95
A Practical Example 101
Conclusion 102
References 112

7 Data Center Management and Good Practices 113

Heinrich Hambloch
The Principle of SOPs and Forms in the
Pharmaceutical Industry 115
Application of SOPs and Forms to Computer Systems 115
A Typical Departmental Computer Center 116
vi Contents

SOPs for the Operation of a Department Computer

Center 117
Summary 133
Reference 140

8 Audit of External Software Vendors 141

Dr. Heinrich Hambloch
The Planning of the Audit 142
The Realization of the Audit 144
Evaluation of the Audit . 154
Summary 155
References 155

9 Clinical Data Systems, GCP Validation,

and CANDA 157
Dr. Ten Stokes
Business Life Cycle for GCP Validation 158
The GCP Difference for Computers 161
Data Systems That Are GCP Regulated 161
Where Companies Usually Start GCP
Systems Validation 162
Membership of the GCP Validation Team 163
The Role of the GCP Validation Team & the Test Plan
Working Group 164
Software Validation Plan for an Existing CRF
Management System 167
GCP Validation and CANDA Support 172
 Contents vii

Conclusion 176
References 176

10 Computerized Laboratory Systems and GLP 179

Dr. Ten Stokes
Point 1—Inventory All Types of Computer Use
in the Laboratory 180
Point 2—Assess GLP Relevance for Specific
Hardware and Software Used 181
Point 3—Establish a General Laboratory QA Policy
for IT Compliance to GLP Standards 181
Point 4—Audit the Development of In-House and
Vendor-Supplied Systems 182
Point 5—Create a Collaborative Philosophy for
QA Computer Audits 186
Point 6—Monitor Ongoing Operation and
Maintenance of Regulated Systems 187
Point 7—Prepare a Standard Procedure for Audits
and Inspections 191
Point 8—Document All Compliance Activities 192
Summary 194
References 194

11 Computerized Systems Validation: Preparation 197

for an FDA Bioprocess Inspection
Ronald C. Branning
SOP for Computerized System Validation 199
Computerized System Validation Protocol 200
Definitions 202
viii Contents

Regulatory Environment 203

Initial Consideration for System Computerization 204
Specifying Computer Systems 206
PMA Life Cycle Approach 206
Computer Control of Bioreactor Processing 213
Conclusion 217
References 219

12 Organization and Training for Validation 221

Ronald C. Branning
Regulatory Requirements 221
Validation Master Plan (VMP) 222

13 A Regulatory Perspective 231

Anthony J. Trill
The Potential Benefits of New Technology 231
Computer Systems Assessment—Inspector Concerns 234
EC GMP Requirements 238
Paperless Systems 243
Quality Assurance of Software and Systems Projects 244
Software Certification 251
Validation of Existing Systems 252
Critical Applications 256
Packaging Line Applications 258
Database Packages and Integrated Systems 259
Evidence of Structured Quality Systems 260
 Contents ix

Preparing for an Inspection 266

Conclusions 268
Acknowledgements 269
References 270

Appendices

A Acronyms 275

B Glossary 279

C Drumbeat™ Analysis 287

D European Commission GMP Annex 11 Analysis 295

E Australian Code of GMP Analysis 301

F Recommended Reading 307

Index 313