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 Digital Transformation and
Regulatory Considerations for
Biopharmaceutical and
Healthcare Manufacturers

Volume 1

Digital Technologies for

Automation and Process
Improvement

To order the book, please visit: go.pda.org/TRANS1

Tim Sandle

PDA
Bethesda, MD, USA

DHI Publishing, LLC

River Grove, IL, USA

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10 9 8 7 6 5 4 3 2 1

ISBN: 978-1-942911-52-4
Copyright © 2021 Tim Sandle All rights reserved.

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If there are any omissions, please contact the publisher.
While every effort has been made by the publisher and the author
to ensure the accuracy of the information expressed in this book, the
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expressed in this book are those of the author and may not represent those
of either Davis Healthcare International or the PDA, its officers, or directors.

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 CONTENTS

1 THE NEW NORMAL? DIGITAL TECHNOLOGIES AND

THE TRANSFORMATION OF PHARMACEUTICALS
AND HEALTHCARE........................................................................ 1
Introduction............................................................................................................................. 1
Why this book and why now?......................................................................................... 6
Digital transformation of pharmaceuticals and healthcare.................................. 7
Summary.................................................................................................................................18
References..............................................................................................................................19

2 AUTOMATING THE PROCESS AND FOSTERING

THE DIGITAL PHARMA COMPANY......................................... 21
Introduction...........................................................................................................................21
What is workplace automation?...................................................................................23
Advantages for pharmaceuticals and healthcare....................................................25
Initiation, systems and models.......................................................................................27
Disruption as a driver for automation.......................................................................29
Examples of automation in pharmaceuticals and healthcare...........................31
Automated workflows......................................................................................................32
Automation engineering...................................................................................................33
Continuous manufacturing..............................................................................................34
Adjusting production processes in real-time...........................................................35
Robotics...................................................................................................................................36
Automating the laboratory.............................................................................................42
Drug discovery.....................................................................................................................44
Medical device and pharmaceutical packaging printing.......................................45
3D printing and bio-engineering...................................................................................46

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iv Digital Transformation and Regulatory Considerations
3D printing and personalized, tablet-form medicines..........................................49
Contract management......................................................................................................51
Information Technology support..................................................................................53
Automation and cybersecurity concerns..................................................................54
Automation: Changing work and job losses............................................................55
Why automation projects may fail..............................................................................57
Risk assessing automation................................................................................................59
Future of automation.........................................................................................................63
Summary.................................................................................................................................63
References..............................................................................................................................64

3 BIG DATA ANALYTICS: COLLECTING PROCESS

AND PRODUCT CENTRIC DATA............................................ 73
Introduction...........................................................................................................................73
What is big data?.................................................................................................................75
Big data analytics..................................................................................................................80
Ethics and big data..............................................................................................................83
Big data strategies...............................................................................................................84
Data science..........................................................................................................................86
Pharmaceuticals and healthcare....................................................................................86
Big data examples................................................................................................................86
Summary.................................................................................................................................97
References..............................................................................................................................98

4 REAL-TIME METRICS: ADVANCES WITH

PROCESS ANALYTICAL TECHNOLOGY..............................105
Introduction........................................................................................................................105
The role of PAT.................................................................................................................108
Regulatory basis of PAT.................................................................................................110
Effective PAT technologies...........................................................................................112
Implementing PAT............................................................................................................113
PAT platforms and digital data....................................................................................115
Examples of PAT...............................................................................................................117
What are metrics?............................................................................................................126
Using metrics......................................................................................................................129
Setting and assessing metrics......................................................................................130
Weakness with metrics..................................................................................................133
Summary..............................................................................................................................133
References...........................................................................................................................135

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 Contents v

5 ULTIMATE PREVENTATIVE MEASURES? THE USE

OF PREDICTIVE ANALYTICS TECHNOLOGY ...................139
Introduction........................................................................................................................139
Why predictive analytics?..............................................................................................142
Regulatory inspections as predictors for GMP issues......................................142
Predictive analytics models..........................................................................................144
Pharma 4.0..........................................................................................................................148
Implementation.................................................................................................................149
Applications of predictive analytics..........................................................................150
Predictive manufacturing...............................................................................................155
Predictive maintenance..................................................................................................158
SAP.........................................................................................................................................162
Analyzing competitor behavior..................................................................................163
Pharmaceutical product marketing...........................................................................163
Clinical trials and drug discovery...............................................................................164
Lessons from the food industry.................................................................................167
Errors with predictive models....................................................................................170
Summary..............................................................................................................................171
References...........................................................................................................................173

6 THE NEW VISION USE OF DIGITAL TWINS

AND VIRTUAL REALITY...........................................................181
Introduction........................................................................................................................181
Virtual reality......................................................................................................................183
Augmented reality............................................................................................................189
Augmented reality and the cleanroom...................................................................190
Augmented reality and patient outcomes.............................................................191
Augmented reality and training..................................................................................192
Augmented reality and pharmaceutical sales.......................................................192
Augmented reality and healthcare manufacturing..............................................193
Augmented reality and medical procedures.........................................................195
Augmented reality and “smart” glasses..................................................................196
Digital twins........................................................................................................................198
Process digital twins........................................................................................................200
Digital Twins: Reducing and addressing out-of-specification results...........201
Digital twins and drug development........................................................................202
Digital twins and logistics..............................................................................................203
Data based collected to support digital twin models......................................204
Adoption challenges........................................................................................................205

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vi Digital Transformation and Regulatory Considerations
Summary..............................................................................................................................209
References...........................................................................................................................209

7 SECURING DATA COLLECTION: ADOPTION

OF WIRELESS TECHNOLOGY AND CLOUD
COMPUTING IN PHARMA.......................................................217
Introduction........................................................................................................................217
Wi-Fi......................................................................................................................................218
Application of wireless technology in the pharmaceutical facility
and for healthcare............................................................................................................226
Concerns in relation to wireless deployment in pharmaceuticals..............234
Wireless concern #1: Data security........................................................................235
Wireless concern #2: Data integrity.......................................................................237
Wireless concern #3: Cyberattacks.........................................................................240
Wireless concern #4: Disruption of data signals...............................................244
Wireless concern #5: Data privacy..........................................................................244
Risk assessment.................................................................................................................246
Conclusion...........................................................................................................................246
References...........................................................................................................................247

8 KEY CONSIDERATIONS FOR THE ADOPTION

AND OPERATION OF ELECTRONIC
BATCH RECORDS.......................................................................253
Introduction........................................................................................................................253
Pharmaceutical batch records.....................................................................................254
Electronic batch records...............................................................................................255
GMP considerations........................................................................................................260
Data integrity.....................................................................................................................263
Auditing.................................................................................................................................265
Future state: blockchain.................................................................................................269
Summary..............................................................................................................................269
References...........................................................................................................................270

9 ARTIFICIAL INTELLIGENCE AND

THE DRUG DEVELOPMENT PROCESS.................................273
Introduction........................................................................................................................273
What is AI?..........................................................................................................................275
Drug development...........................................................................................................279
Artificial intelligence advances drug development medical science............281

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 Contents vii
Other technologies to advance drug discovery..................................................300
Summary..............................................................................................................................303
References...........................................................................................................................304

10 BLOCKCHAIN, TRACK AND TRACE TECHNOLOGY

AND COUNTERFEIT MEDICINES..........................................309
Introduction........................................................................................................................309
Supply chain........................................................................................................................312
Global concerns with falsified medicines...............................................................316
Regulatory responses......................................................................................................316
Using new technologies.................................................................................................323
Summary..............................................................................................................................343
References...........................................................................................................................345

GLOSSARY OF DIGITAL TRANSFORMATION TERMS................353

Sources..................................................................................................................................366

INDEX.......................................................................................................367

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