Pharmaceutical Industry 4.

0: Future,
Challenges & Application
RIVER PUBLISHERS SERIES IN BIOTECHNOLOGY AND
MEDICAL RESEARCH

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Pharmaceutical Industry 4.0: Future,
Challenges & Application

Editors

Rishabha Malviya
School of Medical and Allied Sciences
Galgotias University, Greater Noida, India

Sonali Sundram
School of Medical and Allied Sciences
Galgotias University, Greater Noida, India

Shivkanya Fuloria
AIMST University, Malaysia

Dhanalekshmi Unnikrishnan Meenakshi

National University of Science and Technology
Muscat, Sultanate of Oman

River Publishers
 Published 2023 by River Publishers
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Pharmaceutical Industry 4.0: Future, Challenges & Application / by

Rishabha Malviya, Sonali Sundram, Shivkanya Fuloria, Dhanalekshmi
Unnikrishnan Meenakshi.

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 Contents

Preface xix

Acknowledgement xxi

List of Figures xxiii

List of Tables xxv

List of Contributors xxvii

List of Abbreviations xxxi

1 Digitalization in the Pharmaceutical Industry: Prioritization

Throughout the Digital Transformation 1
Sudhanshu Mishra, Shalini Yadav, Nishita Singh, Rajiv Dahiya,
and Swati Verma
1.1 Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . 2
1.2 Good Manufacturing Practice (GMP) within
Pharmaceuticals . . . . . . . . . . . . . . . . . . . . . . . . 3
1.2.1 Enforcement of GMP . . . . . . . . . . . . . . . . . 4
1.2.2 The pharmaceutical industry’s five GMP
principles . . . . . . . . . . . . . . . . . . . . . . . 4
1.2.2.1 People . . . . . . . . . . . . . . . . . . . 5
1.2.2.2 Procedures . . . . . . . . . . . . . . . . . 6
1.2.2.3 Process . . . . . . . . . . . . . . . . . . . 6
1.2.2.4 Premises and equipment . . . . . . . . . . 6
1.2.2.5 Products . . . . . . . . . . . . . . . . . . 7
1.3 Traditional Drug Production vs. Contract Development and
Manufacturing . . . . . . . . . . . . . . . . . . . . . . . . . 7
1.4 Digitalization of CDMO . . . . . . . . . . . . . . . . . . . 8
1.5 Opportunities . . . . . . . . . . . . . . . . . . . . . . . . . 9

v
vi Contents

1.5.1 To put it another way, productivity . . . . . . . . . . 10

1.5.2 The product’s quality . . . . . . . . . . . . . . . . . 11
1.5.3 Control . . . . . . . . . . . . . . . . . . . . . . . . 11
1.5.4 Cost-effectiveness . . . . . . . . . . . . . . . . . . 12
1.6 Challenges . . . . . . . . . . . . . . . . . . . . . . . . . . . 12
1.7 Execution of the Digital Transformation . . . . . . . . . . . 13
1.7.1 Focus on value . . . . . . . . . . . . . . . . . . . . 13
1.7.2 Holding the adaptability . . . . . . . . . . . . . . . 14
1.7.3 Prioritize the quality . . . . . . . . . . . . . . . . . 14
1.7.4 Standardization of process . . . . . . . . . . . . . . 15
1.7.5 An illustration of digitalization . . . . . . . . . . . . 16
1.8 Conclusions . . . . . . . . . . . . . . . . . . . . . . . . . . 16

2 Applications of Industry 4.0 in the Pharmaceutical Sector 25

Urvashi Sharma, Nitu Singh, Poojashree Verma,
Sumeet Dwivedi, Neelam Jain, and Javed Ahamad
2.1 Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . 26
2.1.1 Industrial revolutions in different
eras . . . . . . . . . . . . . . . . . . . . . . . . . . 27
2.1.2 Industry 4.0 . . . . . . . . . . . . . . . . . . . . . . 28
2.1.3 Benefits of Industry 4.0 . . . . . . . . . . . . . . . . 29
2.1.4 Technological pillars of Industry 4.0 . . . . . . . . . 32
2.2 Pharma 4.0 . . . . . . . . . . . . . . . . . . . . . . . . . . 36
2.2.1 Elements of Pharma 4.0 . . . . . . . . . . . . . . . 38
2.3 Applications of Industry 4.0 to Pharmaceutical
Sectors . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 40
2.3.1 Continuous manufacturing . . . . . . . . . . . . . . 41
2.3.2 Customized drugs and
biopharmaceuticals . . . . . . . . . . . . . . . . . . 43
2.3.3 Digitally enabled laboratories . . . . . . . . . . . . 45
2.3.4 Drug discovery . . . . . . . . . . . . . . . . . . . . 46
2.3.5 Healthcare . . . . . . . . . . . . . . . . . . . . . . 48
2.3.6 Pharmaceutical logistics . . . . . . . . . . . . . . . 49
2.3.7 Quality assurance . . . . . . . . . . . . . . . . . . . 51
2.3.8 Quality management . . . . . . . . . . . . . . . . . 51
2.3.9 Packaging sector . . . . . . . . . . . . . . . . . . . 53
2.4 Service Providers of Industry 4.0 to Pharmaceutical
Sectors . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 54
2.5 Conclusion . . . . . . . . . . . . . . . . . . . . . . . . . . 54
 Contents vii

3 Blockchain in Pharmaceutical Industry: Opportunities

and Challenges 65
Deepika Bairagee, Poojashree Verma, Gaurav Saraogi,
Neelam Jain, Neetesh Kumar Jain, and Mohammad Javed Naim
3.1 Introduction to Blockchain . . . . . . . . . . . . . . . . . . 66
3.1.1 Definition of blockchain . . . . . . . . . . . . . . . 68
3.2 Cryptography . . . . . . . . . . . . . . . . . . . . . . . . . 69
3.2.1 Unkeyed encryption . . . . . . . . . . . . . . . . . 69
3.2.2 Symmetric-key encryption . . . . . . . . . . . . . . 70
3.2.3 Asymmetric-key encryption . . . . . . . . . . . . . 71
3.2.4 Signatures . . . . . . . . . . . . . . . . . . . . . . . 71
3.3 Characteristics of Blockchain . . . . . . . . . . . . . . . . . 71
3.3.1 Trust . . . . . . . . . . . . . . . . . . . . . . . . . 72
3.3.2 Decentralization . . . . . . . . . . . . . . . . . . . 72
3.4 Blockchain Structure . . . . . . . . . . . . . . . . . . . . . 73
3.4.1 Blockchain . . . . . . . . . . . . . . . . . . . . . . 73
3.4.2 Block . . . . . . . . . . . . . . . . . . . . . . . . . 73
3.4.3 Transaction . . . . . . . . . . . . . . . . . . . . . . 74
3.5 Applications . . . . . . . . . . . . . . . . . . . . . . . . . . 75
3.5.1 Blockchain in electronic health records
(EHR) . . . . . . . . . . . . . . . . . . . . . . . . . 75
3.5.2 Blockchain in clinical research . . . . . . . . . . . . 78
3.5.3 Blockchains in medical fraud detection . . . . . . . 78
3.5.4 Neuroscience blockchains . . . . . . . . . . . . . . 79
3.5.5 Blockchains in pharmaceutical industry and
research . . . . . . . . . . . . . . . . . . . . . . . . 80
3.6 Challenges . . . . . . . . . . . . . . . . . . . . . . . . . . . 81
3.6.1 Safety and confidentiality of data . . . . . . . . . . 82
3.6.2 Storage capacity management . . . . . . . . . . . . 83
3.6.3 Interoperability issues . . . . . . . . . . . . . . . . 83
3.6.4 Standardization challenges . . . . . . . . . . . . . . 83
3.6.5 Social challenges . . . . . . . . . . . . . . . . . . . 83
3.7 Future Perspectives . . . . . . . . . . . . . . . . . . . . . . 86
3.8 Implications and Conclusions . . . . . . . . . . . . . . . . . 87

4 Patient Monitoring using Blockchain 95

P. Jayasree, AVSSS Gupta, GSN Koteswara Rao, Hajeera
Fatima, Rekha Naresh Babu, and Roja Rani Budha
4.1 Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . 96
viii Contents

4.2 Blockchain Technology . . . . . . . . . . . . . . . . . . . . 98

4.2.1 Applications of blockchain . . . . . . . . . . . . . . 98
4.2.1.1 Blockchain in healthcare . . . . . . . . . 98
4.2.2 The benefits of blockchain for healthcare systems are
as follows . . . . . . . . . . . . . . . . . . . . . . . 99
4.3 Patient Monitoring System (PMS) . . . . . . . . . . . . . . 100
4.3.1 Use of PMS . . . . . . . . . . . . . . . . . . . . . . 101
4.4 Data Sharing between Telemedicine and Traditional
Care . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 102
4.5 IoT-Blockchain in Remote Patient Monitoring (RPM) . . . . 102
4.6 Framework RPM System with IoT and Blockchain . . . . . 103
4.6.1 Components of the framework . . . . . . . . . . . . 103
4.7 Conclusion . . . . . . . . . . . . . . . . . . . . . . . . . . 104

5 Potential of AI in the Advancement of Pharmaceutical

Industry 107
Akanksha Sharma, Aditi Singh, Ashish Verma, Rishabha Malviya,
and Pavan Kumar Arya Padarthi
5.1 Introduction and History . . . . . . . . . . . . . . . . . . . 108
5.2 Opportunities in the Pharmaceutical Industry for Artificial
Intelligence . . . . . . . . . . . . . . . . . . . . . . . . . . 111
5.2.1 Role of AI in drug development . . . . . . . . . . . 111
5.2.2 Drug screening using artificial intelligence . . . . . 112
5.2.3 Prediction of physicochemical characteristics . . . . 113
5.2.4 Prediction of bioactivity . . . . . . . . . . . . . . . 113
5.2.5 Prediction of ADMET using AI . . . . . . . . . . . 114
5.2.6 Prediction of toxicity . . . . . . . . . . . . . . . . . 116
5.3 AI in Drug Molecule Designing . . . . . . . . . . . . . . . 117
5.3.1 Prediction of target protein structure . . . . . . . . . 117
5.3.2 Predicting drug–protein interactions . . . . . . . . . 118
5.3.3 AI in de novo drug design . . . . . . . . . . . . . . 118
5.4 AI in Diagnosis . . . . . . . . . . . . . . . . . . . . . . . . 119
5.4.1 Cardiovascular disease (CVD) . . . . . . . . . . . . 121
5.4.1.1 Precision medicine . . . . . . . . . . . . . 121
5.4.1.2 Cardiac imaging analysis . . . . . . . . . 121
5.4.2 Cancer . . . . . . . . . . . . . . . . . . . . . . . . 122
5.4.2.1 Solid tumor diagnosis . . . . . . . . . . . 122
5.4.2.2 Non-solid tumor diagnosis . . . . . . . . 123
5.4.3 Fractures . . . . . . . . . . . . . . . . . . . . . . . 124
 Contents ix

5.4.4 Tuberculosis . . . . . . . . . . . . . . . . . . . . . 125

5.4.5 Diabetes . . . . . . . . . . . . . . . . . . . . . . . . 128
5.4.6 Stroke . . . . . . . . . . . . . . . . . . . . . . . . . 129
5.4.7 Skin disease . . . . . . . . . . . . . . . . . . . . . . 130
5.4.7.1 Skin cancer . . . . . . . . . . . . . . . . 130
5.4.7.2 Atopic dermatitis . . . . . . . . . . . . . 131
5.4.7.3 Psoriasis . . . . . . . . . . . . . . . . . . 131
5.5 Challenges to the Adoption of Artificial Intelligence in
Pharma . . . . . . . . . . . . . . . . . . . . . . . . . . . . 132
5.5.1 Main obstacles related to AI in Pharma
industry . . . . . . . . . . . . . . . . . . . . . . . . 133
5.5.2 Unifying problem . . . . . . . . . . . . . . . . . . . 134
5.5.3 Insufficient skillsets . . . . . . . . . . . . . . . . . 134
5.5.4 Scientific approach . . . . . . . . . . . . . . . . . . 134
5.5.5 Absence of investment . . . . . . . . . . . . . . . . 134
5.5.6 Some other issues of concern . . . . . . . . . . . . . 135
5.6 Conclusion . . . . . . . . . . . . . . . . . . . . . . . . . . 135

6 Use of Artificial Intelligence and Robotics: Making Drug

Development Process Easier 145
Aditi Singh, Ashish Verma, Akanksha Sharma, Rishabha Malviya,
and Mahendran Sekar
6.1 Introduction and History of AI in Drug Development . . . . 146
6.1.1 History behind AI . . . . . . . . . . . . . . . . . . 147
6.1.2 AI platforms for target identification . . . . . . . . . 148
6.1.2.1 DisGeNET . . . . . . . . . . . . . . . . . 148
6.1.2.2 LinkedOmics . . . . . . . . . . . . . . . 148
6.1.2.3 DepMap portal . . . . . . . . . . . . . . . 148
6.1.2.4 Therapeutic target database . . . . . . . . 148
6.1.2.5 Positivity in AI . . . . . . . . . . . . . . . 149
6.2 Introduction and History of Robotics in Healthcare, Drug
Discovery . . . . . . . . . . . . . . . . . . . . . . . . . . . 149
6.2.1 Decade I (first generations): 1990–2000 . . . . . . . 150
6.2.1.1 neuromate . . . . . . . . . . . . . . . . . 150
6.2.1.2 ROBODOC Surgical System . . . . . . . 150
6.2.1.3 AESOPTM robotic surgical system . . . . 150
6.2.1.4 CyberKnife system . . . . . . . . . . . . 151
6.2.1.5 ZEUS robotic surgical system . . . . . . . 151
6.2.1.6 CASPAR . . . . . . . . . . . . . . . . . 151
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6.2.2 Decade II (middle generations): 2000–2010 . . . . . 151

6.2.2.1 AcuBot . . . . . . . . . . . . . . . . . . . 151
6.2.2.2 PathFinderTM . . . . . . . . . . . . . . . 151
6.2.2.3 InnoMotion . . . . . . . . . . . . . . . . 151
6.2.3 Decade III (new generations): 2010–Present . . . . . 152
6.2.3.1 ROSA ONE . . . . . . . . . . . . . . . . 152
6.2.3.2 PRECEYES Surgical System . . . . . . . 152
6.2.3.3 IonTM robotic-assisted
platform . . . . . . . . . . . . . . . . . . 152
6.3 Application of Robotics in the Healthcare
Sector . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 152
6.4 AI in Research and Development . . . . . . . . . . . . . . . 152
6.4.1 Target validation . . . . . . . . . . . . . . . . . . . 154
6.4.2 Lead identification . . . . . . . . . . . . . . . . . . 154
6.4.3 Preclinical trials and clinical trials . . . . . . . . . . 154
6.4.4 De novo drug design . . . . . . . . . . . . . . . . . 155
6.5 Pharmaceutical Product Developments . . . . . . . . . . . . 155
6.5.1 Nanorobots drug delivery . . . . . . . . . . . . . . . 155
6.5.1.1 Pharmacyte . . . . . . . . . . . . . . . . 158
6.5.1.2 Respirocyte . . . . . . . . . . . . . . . . 159
6.5.1.3 Clottocytes . . . . . . . . . . . . . . . . . 160
6.5.2 Controlled-release formulations . . . . . . . . . . . 161
6.5.3 Pharmaceutical product R&D . . . . . . . . . . . . 161
6.5.4 Controlled insulin release . . . . . . . . . . . . . . 162
6.5.5 Combination drug delivery . . . . . . . . . . . . . . 163
6.5.6 Nanomedicine . . . . . . . . . . . . . . . . . . . . 164
6.6 AI Tools for Drug Discovery Phase . . . . . . . . . . . . . . 165
6.6.1 Deep Chem . . . . . . . . . . . . . . . . . . . . . . 165
6.6.2 Deep Neural Net QSAR . . . . . . . . . . . . . . . 166
6.6.3 DeepTox . . . . . . . . . . . . . . . . . . . . . . . 168
6.6.4 Graph neural networks . . . . . . . . . . . . . . . . 169
6.6.5 PotentialNet . . . . . . . . . . . . . . . . . . . . . 170
6.7 AI in Drug Discovery Process . . . . . . . . . . . . . . . . 170
6.7.1 Drug screening . . . . . . . . . . . . . . . . . . . . 170
6.7.2 Drug design . . . . . . . . . . . . . . . . . . . . . . 172
6.7.3 Drug repurposing . . . . . . . . . . . . . . . . . . . 173
6.7.4 Polypharmacology . . . . . . . . . . . . . . . . . . 174
6.8 Future of Robotics and AI . . . . . . . . . . . . . . . . . . 175
6.9 Conclusion . . . . . . . . . . . . . . . . . . . . . . . . . . 176
 Contents xi

7 Pharmaceutical Packaging: New Impulse through

Artificial Intelligence 187
Smriti Ojha, Anubhav Anand, Manoj Saini, Sudhanshu Mishra,
and Kamal Dua
7.1 Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . 188
7.2 Role of AI in Pharmaceutical Packaging . . . . . . . . . . . 190
7.3 Defect Identification . . . . . . . . . . . . . . . . . . . . . 190
7.4 Data Labeling . . . . . . . . . . . . . . . . . . . . . . . . . 195
7.5 Warehouse Automation . . . . . . . . . . . . . . . . . . . . 196
7.6 Optimization of Product Packaging with AI . . . . . . . . . 196
7.7 AI-assisted Designing for Aesthetic Packaging . . . . . . . 197
7.8 AI-assisted Selection of Packaging Material . . . . . . . . . 197
7.9 AI Integrated Approaches Used in Pharmaceutical
Packaging . . . . . . . . . . . . . . . . . . . . . . . . . . . 198
7.9.1 Convolutional neural network approach
(CNN pack) . . . . . . . . . . . . . . . . . . . . . . 198
7.9.2 Computer vision approach . . . . . . . . . . . . . . 198
7.9.3 Statistical approach . . . . . . . . . . . . . . . . . . 198
7.9.4 Structural approach . . . . . . . . . . . . . . . . . . 199
7.9.5 Filter approach . . . . . . . . . . . . . . . . . . . . 199
7.9.6 Model-based approach . . . . . . . . . . . . . . . . 199
7.10 Critical Features of AI-assisted Packaging . . . . . . . . . . 199
7.10.1 Cloud computing . . . . . . . . . . . . . . . . . . . 199
7.10.2 Security . . . . . . . . . . . . . . . . . . . . . . . . 200
7.10.3 Assistance . . . . . . . . . . . . . . . . . . . . . . 200
7.10.4 Monitoring . . . . . . . . . . . . . . . . . . . . . . 200
7.10.5 Advantages of AI-assisted Packaging . . . . . . . . 200
7.10.6 Packaging prototypes in 3D space with the aid of
AI . . . . . . . . . . . . . . . . . . . . . . . . . . . 200
7.10.7 Designing as per product’s needs . . . . . . . . . . . 200
7.10.8 Packaging of different shapes and sizes for specific
products (Sheng & Wang, 2022b) . . . . . . . . . . 201
7.10.9 Packaging with RFID tags or QR codes . . . . . . . 201
7.10.10 AI-driven automation with controlling robots . . . . 201
7.10.11 Sensors for temper resistant packaging . . . . . . . . 201
7.10.12 Optimization of production lines and
processes . . . . . . . . . . . . . . . . . . . . . . . 202
7.10.13 Sustainable packaging practices . . . . . . . . . . . 202
7.10.14 Preventative maintenance . . . . . . . . . . . . . . . 202
xii Contents

7.10.15 Use of augmented reality (AR) and virtual

reality (VR) . . . . . . . . . . . . . . . . . . . . . . 202
7.11 Components for AI-assisted Packaging . . . . . . . . . . . . 203
7.11.1 Big data . . . . . . . . . . . . . . . . . . . . . . . . 203
7.11.2 Processing power . . . . . . . . . . . . . . . . . . . 203
7.11.3 Connected globe . . . . . . . . . . . . . . . . . . . 203
7.11.4 Software . . . . . . . . . . . . . . . . . . . . . . . 204
7.11.5 Algorithms and problem-solving operations . . . . . 204
7.12 Conclusion . . . . . . . . . . . . . . . . . . . . . . . . . . 204

8 Digital Assistant in Pharmaceutical Field Advancing

Healthcare System 213
Ashish Verma, Akanksha Sharma, Aditi Singh, Rishabha Malviya,
and Neeraj Kumar Fuloria
8.1 Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . 214
8.2 Digital Assistants’ Role in the Healthcare System . . . . . . 219
8.2.1 For psychological therapy . . . . . . . . . . . . . . 219
8.2.2 Symptoms diagnosis and patient triage . . . . . . . 220
8.2.3 Digital assistant for treatment monitoring . . . . . . 222
8.3 Electronic Health Record (EHR) . . . . . . . . . . . . . . . 223
8.3.1 Benefits of EHR . . . . . . . . . . . . . . . . . . . 224
8.3.2 Ways to differentiate an electronic health record from
a paper-based record . . . . . . . . . . . . . . . . . 224
8.3.3 Initiatives by the Government of India . . . . . . . . 225
8.4 Personal Health Record (PHR) . . . . . . . . . . . . . . . . 226
8.4.1 PHR advantages . . . . . . . . . . . . . . . . . . . 226
8.4.1.1 Keep track of health and evaluate it . . . . 226
8.4.1.2 Make the utmost of physician visits . . . . 226
8.4.1.3 Manage health between physician
visits . . . . . . . . . . . . . . . . . . . . 227
8.4.1.4 Get systematized . . . . . . . . . . . . . . 227
8.5 Medical Practice Management (MPM) Software . . . . . . . 227
8.5.1 Applications of patient management system/medical
practice management system . . . . . . . . . . . . . 228
8.6 Big Data in Biomedical Research . . . . . . . . . . . . . . . 228
8.6.1 Applications of big data . . . . . . . . . . . . . . . 229
8.6.2 Platform for big data (Hadoop cluster) . . . . . . . . 230
8.6.2.1 Storage . . . . . . . . . . . . . . . . . . . 230
8.6.2.2 Processing (MapReduce) . . . . . . . . . 231
 Contents xiii

8.7 Internet of Things (IoT) and their Advantages in

Healthcare . . . . . . . . . . . . . . . . . . . . . . . . . . . 231
8.7.1 IoT-based healthcare architecture . . . . . . . . . . 232
8.7.1.1 Perception layer: data-collecting sensing
systems . . . . . . . . . . . . . . . . . . 232
8.7.1.2 Network layer: data communication and
storage . . . . . . . . . . . . . . . . . . . 233
8.7.1.3 Application Layer . . . . . . . . . . . . . 234
8.8 Artificial Intelligence in Biomedical Engineering . . . . . . 234
8.8.1 AI in living assistance . . . . . . . . . . . . . . . . 235
8.8.2 AI in biomedical information processing . . . . . . 235
8.8.3 AI in biomedical research . . . . . . . . . . . . . . 236
8.9 AI in Diagnosis and Prediction . . . . . . . . . . . . . . . . 237
8.10 Blockchain Taxonomy . . . . . . . . . . . . . . . . . . . . 240
8.10.1 Public blockchains . . . . . . . . . . . . . . . . . . 240
8.10.2 Private blockchains . . . . . . . . . . . . . . . . . . 240
8.10.3 Consortium blockchain . . . . . . . . . . . . . . . . 240
8.10.4 Hybrid blockchains . . . . . . . . . . . . . . . . . . 240
8.11 Blockchain Use Cases in Healthcare . . . . . . . . . . . . . 240
8.11.1 Blockchain in remote patient
monitoring . . . . . . . . . . . . . . . . . . . . . . 240
8.11.2 Pharmaceutical supply chain . . . . . . . . . . . . . 242
8.11.3 Health insurance claims . . . . . . . . . . . . . . . 243
8.12 Telemedicine and Its Advantages . . . . . . . . . . . . . . . 245
8.13 Conclusion . . . . . . . . . . . . . . . . . . . . . . . . . . 246

9 Deep Learning Techniques and Drug Release 259

Shilpa Singh, Shilpa Rawat, Rishabha Malviya, Sonali Sundram,
and Sunita Dahiya
9.1 Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . 260
9.2 Drug Development . . . . . . . . . . . . . . . . . . . . . . 262
9.3 Basics of Machine Learning . . . . . . . . . . . . . . . . . 263
9.4 Deep Learning . . . . . . . . . . . . . . . . . . . . . . . . 264
9.5 The Evolvement of Deep Learning . . . . . . . . . . . . . . 265
9.5.1 Deep learning techniques . . . . . . . . . . . . . . . 266
9.5.2 Artificial neural networks . . . . . . . . . . . . . . 266
9.5.3 Deep neural networks . . . . . . . . . . . . . . . . 267
9.5.4 Convolutional neural networks . . . . . . . . . . . . 267
9.5.5 Autoencoders . . . . . . . . . . . . . . . . . . . . . 268
xiv Contents

9.5.6 Generative adversarial networks . . . . . . . . . . . 268

9.5.7 Recurrent neural networks . . . . . . . . . . . . . . 268
9.5.8 Restricted Boltzmann machine . . . . . . . . . . . . 269
9.5.9 Dynamic neural network . . . . . . . . . . . . . . . 269
9.5.10 Recurrent neural networks . . . . . . . . . . . . . . 269
9.6 Deep Learning in Bioinformatics . . . . . . . . . . . . . . . 270
9.7 Dissolution and Release of Drug . . . . . . . . . . . . . . . 270
9.7.1 In vitro studies . . . . . . . . . . . . . . . . . . . . 272
9.7.2 In vivo studies . . . . . . . . . . . . . . . . . . . . 272
9.8 Application of Deep Learning in Pharmaceutical
Formulation . . . . . . . . . . . . . . . . . . . . . . . . . . 273
9.9 Application of Deep Learning Releasing of
Drug . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 275
9.10 Predictive Models for Drug Release of Deep
Learning . . . . . . . . . . . . . . . . . . . . . . . . . . . . 278
9.11 Deep Learning Models for Prediction of Drug Release and
Permeation . . . . . . . . . . . . . . . . . . . . . . . . . . 278
9.12 Conclusions . . . . . . . . . . . . . . . . . . . . . . . . . . 279

10 Tissue Response Study using Deep Learning Techniques 293

Akanksha Pandey, Rishabha Malviya, Sonali Sundram, and
Karteek Telikicherla
10.1 Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . 294
10.2 Research Methodologies . . . . . . . . . . . . . . . . . . . 299
10.2.1 Color separation . . . . . . . . . . . . . . . . . . . 299
10.2.2 Detection of cells . . . . . . . . . . . . . . . . . . . 300
10.3 Materials and Procedures . . . . . . . . . . . . . . . . . . . 300
10.3.1 Cohorts of patients . . . . . . . . . . . . . . . . . . 300
10.3.2 Image pre-processing and CT
acquisition . . . . . . . . . . . . . . . . . . . . . . 301
10.3.3 The structure of a neural network . . . . . . . . . . 302
10.3.4 Analytical statistics . . . . . . . . . . . . . . . . . . 303
10.4 Features of the Clinic . . . . . . . . . . . . . . . . . . . . . 304
10.4.1 Development and evaluation of prognostic
biomarkers based on deep learning . . . . . . . . . . 304
10.4.2 Pathological outcome prediction . . . . . . . . . . . 305
10.5 Methodologies/Network Structures . . . . . . . . . . . . . . 306
10.5.1 Convolutional neural networks (CNNs) . . . . . . . 306
 Contents xv

10.5.1.1 CNN in 2D . . . . . . . . . . . . . . . . . 307

10.5.1.2 CNN in 2.5D . . . . . . . . . . . . . . . . 307
10.5.1.3 CNN in 3D . . . . . . . . . . . . . . . . . 308
10.5.2 Convolutional network in its complete form
(FCN) . . . . . . . . . . . . . . . . . . . . . . . . . 309
10.5.2.1 Multiorgan segmentation using
FCN . . . . . . . . . . . . . . . . . . . . 309
10.5.2.2 FCN in a cascade (CFCN) . . . . . . . . . 310
10.5.2.3 FCN focal . . . . . . . . . . . . . . . . . 310
10.5.2.4 FCN with several streams . . . . . . . . . 310
10.5.3 Residual convolutional networks
(CRNs) . . . . . . . . . . . . . . . . . . . . . . . . 310
10.6 Training Deep Models: Challenges . . . . . . . . . . . . . . 312
10.6.1 Overfitting . . . . . . . . . . . . . . . . . . . . . . 312
10.6.2 Time to train . . . . . . . . . . . . . . . . . . . . . 312
10.6.3 Gradient disappearance . . . . . . . . . . . . . . . . 312
10.6.4 Challenges in 3D . . . . . . . . . . . . . . . . . . . 313
10.7 Discussion . . . . . . . . . . . . . . . . . . . . . . . . . . . 313
10.8 Conclusions . . . . . . . . . . . . . . . . . . . . . . . . . . 319

11 Issues and Challenges in Bioinformatics Tool for Clinical

Trials 329
Akanksha Pandey, Rishabha Malviya, Sonali Sundram, and
Vetriselvan Subramaniyan
11.1 Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . 330
11.2 Domain for Biomedical Applications . . . . . . . . . . . . . 334
11.2.1 Outline of the Domain . . . . . . . . . . . . . . . . 335
11.2.1.1 Bioinformatics concepts . . . . . . . . . . 335
11.2.2 Informatics Opportunities and
Questions . . . . . . . . . . . . . . . . . . . . . . . 336
11.2.2.1 Move up in informatics research . . . . . 336
11.2.2.2 Knowledge chances and questions . . . . 337
11.2.2.3 Opportunities and questions . . . . . . . . 341
11.2.2.4 Biomedical chances and
questions . . . . . . . . . . . . . . . . . . 342
11.2.2.5 Conceptual approaches for bioinformatics
platforms . . . . . . . . . . . . . . . . . . 343
11.3 Examples of Uses . . . . . . . . . . . . . . . . . . . . . . . 345
xvi Contents

11.4 ICT as Basic Buildings for Supporting Clinical

Bioinformatics Necessary . . . . . . . . . . . . . . . . . . . 346
11.4.1 Design tables . . . . . . . . . . . . . . . . . . . . . 348
11.4.2 Qualities of healthcare and life sciences created for a
person’s medical substance . . . . . . . . . . . . . . 349
11.4.3 Database pictures . . . . . . . . . . . . . . . . . . . 350
11.4.4 Search for and take-out process to the point databases
from large databases . . . . . . . . . . . . . . . . . 351
11.5 Advantages . . . . . . . . . . . . . . . . . . . . . . . . . . 354
11.6 Disadvantages . . . . . . . . . . . . . . . . . . . . . . . . . 355
11.7 Ethical Concern . . . . . . . . . . . . . . . . . . . . . . . . 357
11.8 Conclusion . . . . . . . . . . . . . . . . . . . . . . . . . . 358

12 Advancement in Artificial Intelligence: Insights and Future

Vision for Pharmacy Profession 367
Prem Shankar Mishra, Rakhi Mishra, Sirisha Pingali, and
Rishabha Malviya
12.1 Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . 368
12.2 Carrier’s Scope in Pharmacy . . . . . . . . . . . . . . . . . 369
12.3 Career Path for Pharmacy Professionals . . . . . . . . . . . 369
12.3.1 Research scientist . . . . . . . . . . . . . . . . . . . 370
12.3.2 Pharmacy manager . . . . . . . . . . . . . . . . . . 370
12.3.3 Regulatory specialist . . . . . . . . . . . . . . . . . 370
12.3.4 Pharmaceutical financial analyst . . . . . . . . . . . 371
12.3.5 Pharmaceutical sales representative . . . . . . . . . 371
12.3.6 Clinical data manager . . . . . . . . . . . . . . . . 371
12.3.7 Career options in pharmaceutical
industry . . . . . . . . . . . . . . . . . . . . . . . . 372
12.4 Future of the Pharmacist . . . . . . . . . . . . . . . . . . . 372
12.5 What Changes Can Artificial Intelligence (AI) Bring to the
Pharma Carrier . . . . . . . . . . . . . . . . . . . . . . . . 373
12.6 The Future of Pharma Industries and Career Opportunities
with Advancement . . . . . . . . . . . . . . . . . . . . . . 374
12.6.1 Carrier in Research and Development . . . . . . . . 375
12.6.2 Carrier in the diagnostic sector . . . . . . . . . . . . 375
12.6.3 Carrier in pharmacology . . . . . . . . . . . . . . . 376
12.6.4 Carrier in health sector . . . . . . . . . . . . . . . . 376
12.6.5 Carrier in clinical trial . . . . . . . . . . . . . . . . 376
12.6.6 Carrier in pharma companies . . . . . . . . . . . . . 376
 Contents xvii

12.6.7 Carrier in medical coding . . . . . . . . . . . . . . . 377

12.6.8 Carrier in medical writing . . . . . . . . . . . . . . 377
12.7 Conclusion . . . . . . . . . . . . . . . . . . . . . . . . . . 377

Index 383

About the Editors 385

 Preface

Today’s pharmaceutical manufacturing technologies continue to evolve as

the internet of things, artificial intelligence, big data, deep learning, cloud
computing, robotics, and advanced computing begin to challenge the tra-
ditional approaches, practices, and business models for the manufacture of
pharmaceuticals. The application of these technologies has the potential to
dramatically improve the efficiency, agility, flexibility, and quality of the
industrial production of medicines.
This book explains how advanced technologies and emerging trends such
as blockchain, robotics, bioinformatics, big data, artificial intelligence, deep
learning, cloud computing, will impact the manufacturing and distribution of
pharmaceuticals in order to build a better future of healthcare.
This book will help many pharmaceutical companies, IT companies and
researchers to explore how evolution of industry 4.0 can be effectively uti-
lized to revolutionize the pharmaceutical sector and healthcare. This book
gives wide variety in topics which represent the opportunity and application
of industry 4.0 in pharmaceutical field. This book contains 12 chapters
subdivided into various section that is written by profound researchers and
academicians from many parts of the world. The book is profusely refer-
enced and copiously illustrated. This should be noted that all chapters were
deliberately reviewed and all were suitably revised once or two times. So,
the content presented in this book is of greatest value and meets the highest
standard of publication.
This book should present useful source for researchers and industrial-
ists working in clinical research, pharmaceutical manufacturing, scientist
working in R&D.
We sincerely believe that the book will prove to be useful contribution to
pharmaceutical science.
Finally comes the best part to thank you everyone who helped to make
this book possible. First and foremost, we express our heartfelt gratitude to
the authors for their contribution, dedication, participation, and willingness to
share their significant research experience in the form of written testimonials,

xix
xx Preface

which would not have been possible without them. lastly, we are feeling
fortunate to express our gratitude to River Publishers for his unwavering
support.

Editors:
Rishabha Malviya
School of Medical and Allied Sciences,
Galgotias University, Greater Noida, India.
Sonali Sundram
School of Medical and Allied Sciences,
Galgotias University, Greater Noida, India.
Shivkanya Fuloria
AIMST University, Malaysia.
Dhanalekshmi Unnikrishnan Meenakshi
National University of Science and Technology,
Muscat, Sultanate of Oman.
 Acknowledgement

Having an idea and turning it into a book is as hard as it sounds. The

experience is both internally challenging and rewarding. At the very outset,
we fail to find adequate words, with limited vocabulary to our command, to
express our emotion to almighty, whose eternal blessing, divine presence, and
masterly guidelines helps us to fulfill all our goals.
When emotions are profound, words sometimes are not sufficient to
express our thanks and gratitude. We especially want to thank the individuals
that helped make this happen. Without the experiences and support from my
peers and team, this book would not exist.
No words can describe the immense contribution of our parents, friends,
without whose support this work would have not been possible.
Last but not least, we would like to thank, our publisher for their support,
innovative suggestions and guidance in bringing out this edition.

xxi
 List of Figures

Figure 1.1 Schematic representation of 5Ps of GMP. . . . . . 5

Figure 1.2 Opportunities and challenges of digitalization. . . . 9
Figure 2.1 Evolution of Industries 4.0. . . . . . . . . . . . . . 28
Figure 2.2 Elements of Pharma 4.0. . . . . . . . . . . . . . . 39
Figure 2.3 Applications of Industry 4.0 in the pharmaceutical
sector. . . . . . . . . . . . . . . . . . . . . . . . . 41
Figure 2.4 Representation of a comparison between continuous
manufacturing and batch manufacturing. . . . . . . 42
Figure 3.1 A general workflow of the blockchain method. . . . 67
Figure 3.2 Blockchain characteristics. . . . . . . . . . . . . . 72
Figure 3.3 Simplified blockchain structure . . . . . . . . . . . 74
Figure 3.4 Blockchains in healthcare applications . . . . . . . 76
Figure 3.5 Blockchains in healthcare: opportunities and
challenges . . . . . . . . . . . . . . . . . . . . . . 82
Figure 3.6 Blockchains in healthcare: a SWOT analysis . . . . 84
Figure 4.1 Benefits of blockchain for healthcare systems. . . . 100
Figure 5.1 The schematic diagram represents the summary of
the utilization of AI in drug discovery. . . . . . . . 111
Figure 5.2 Schematic diagram of AI-guided prediction of
ADMET. . . . . . . . . . . . . . . . . . . . . . . . 115
Figure 5.3 A schematic diagram shows the AI utilization in the
diagnosis of various diseases. . . . . . . . . . . . . 120
Figure 6.1 Schematic diagram to show the AI importance in
research and development. . . . . . . . . . . . . . 153
Figure 6.2 The schematic diagram summarizes the various
pharmaceutical products that are developed by the
utilization of AI and robotics. . . . . . . . . . . . . 156
Figure 6.3 Schematic diagram of a few nanorobots which help
in the delivery of drugs and therapies. . . . . . . . 158
Figure 6.4 Schematic diagram shows the drug discovery
process. . . . . . . . . . . . . . . . . . . . . . . . 171

xxiii
xxiv List of Figures

Figure 7.1 Types of machine learning. . . . . . . . . . . . . . 189

Figure 7.2 Visual-based defect detection. . . . . . . . . . . . 191
Figure 7.3 Object representation for AI-assisted image
analysis. . . . . . . . . . . . . . . . . . . . . . . . 192
Figure 7.4 The lifecycle of machine learning. . . . . . . . . . 193
Figure 8.1 Illustration of the function of electronic health
records. . . . . . . . . . . . . . . . . . . . . . . . 225
Figure 8.2 The schematic figure shows the benefits of PHR. . . 227
Figure 8.3 Three core layers of IoT architecture help in
healthcare delivery. . . . . . . . . . . . . . . . . . 233
Figure 9.1 A comparison of the relationships among AI, deep
learning, and machine learning. . . . . . . . . . . . 261
Figure 9.2 Application of machine learning in the
pharmaceutical industry. . . . . . . . . . . . . . . 264
Figure 9.3 Drug dissolution and drug release process. . . . . . 271
Figure 9.4 Application of deep learning in the pharmaceutical
industry. . . . . . . . . . . . . . . . . . . . . . . . 274
Figure 10.1 Representing the way of providing treatment by the
method advanced diagnosis approach. . . . . . . . 297
Figure 10.2 Approaches of research methodologies. . . . . . . 299
Figure 10.3 Identification of tumor cells by the advanced
diagnosis method. . . . . . . . . . . . . . . . . . . 306
Figure 10.4 A screening method for the diagnosis. . . . . . . . 311
Figure 11.1 Components of bioinformatics. . . . . . . . . . . . 334
Figure 11.2 Advantages and role of bioinformatics and software
tools in clinical research. . . . . . . . . . . . . . . 355
Figure 12.1 Application of AI in the health and pharmaceutical
sector. . . . . . . . . . . . . . . . . . . . . . . . . 374
Figure 12.2 Career opportunities due to implications of AI. . . . 375
 List of Tables

Table 2.1 Comparison of digital maturity models in different

industrial evolutions. . . . . . . . . . . . . . . . . . . 40
Table 2.2 Major pharmaceutical companies employing Pharma
4.0 concept. . . . . . . . . . . . . . . . . . . . . . . 43
Table 2.3 Service providers of Industry 4.0. . . . . . . . . . . . 55
Table 3.1 Blockchain technology’s main components. . . . . . . 67
Table 3.2 Blockchain technology’s applications in
healthcare. . . . . . . . . . . . . . . . . . . . . . . . 81
Table 5.1 Summary of AI application in different fields of
health. . . . . . . . . . . . . . . . . . . . . . . . . . 110
Table 5.2 Characteristics of diabetes care using Machine
Learning and Artificial Intelligence. . . . . . . . . . . 126
Table 6.1 Various tools are utilized in drug discovery
procedures. . . . . . . . . . . . . . . . . . . . . . . . 147
Table 6.2 Application of robotics in the healthcare sector. . . . . 152
Table 7.1 Example of AI-assisted software used in
pharmaceutical packaging. . . . . . . . . . . . . . . . 195
Table 7.2 AI-assisted sorting and identification of packaging
defects. . . . . . . . . . . . . . . . . . . . . . . . . . 195
Table 8.1 Benefits of electronic health record. . . . . . . . . . . 224
Table 8.2 Goals of EHR standards. . . . . . . . . . . . . . . . . 225
Table 9.1 Recent progress of deep and machine learning in
formulation design. . . . . . . . . . . . . . . . . . . 273
Table 10.1 Datasets of different diagnosis patterns. . . . . . . . . 309
Table 11.1 Tools for analyzing biological sequences. . . . . . . . 359

xxv
 List of Contributors

Ahamad, Javed, Department of Pharmacognosy, Faculty of Pharmacy, Tishk

International University, Iraq
Anand, Anubhav, Department of Pharmaceutics, Hygia Institute of Phar-
maceutical Education and Research, India
Babu, Rekha Naresh, Nirmala College of Pharmacy, India
Bairagee, Deepika, Oriental College of Pharmacy and Research, Oriental
University, India
Budha, Roja Rani, Department of Pharmacology, Institute of Pharmaceuti-
cal Technology, Sri Padmavati Mahila Visvavidyalayam, India
Dahiya, Rajiv, School of Pharmacy, Faculty of Medical Sciences, The
University of the West Indies, Trinidad & Tobago
Dahiya, Sunita, Department of Pharmaceutical Sciences, School of Phar-
macy, University of Puerto Rico, USA
Dua, Kamal, Faculty of Health, Australian Research Centre in Complemen-
tary and Integrative Medicine, University of Technology Sydney, Australia
Dwivedi, Sumeet, Faculty of Pharmacy, Oriental University, India
Fatima, Hajeera, Joginpally B.R. Pharmacy College, India
Fuloria, Neeraj Kumar, Faculty of Pharmacy, AIMST University, Malaysia
Gupta, AVSSS, Joginpally B.R. Pharmacy College, India
Jain, Neelam, Faculty of Pharmacy, Oriental University, India
Jain, Neetesh Kumar, Oriental College of Pharmacy and Research, Oriental
University, India
Jayasree, P., Joginpally B.R. Pharmacy College, India
Malviya, Rishabha, Department of Pharmacy, School of Medical and Allied
Sciences, Galgotias University, India

xxvii
xxviii List of Contributors

Mishra, Prem Shankar, School of Medical and Allied Sciences, Galgotias

University, India
Mishra, Rakhi, Noida Institute of Engineering and Technology (Pharmacy
Institute), India
Mishra, Sudhanshu, Department of Pharmaceutical Science & Technology,
Madan Mohan Malaviya University of Technology, India
Naim, Mohammad Javed, Department of pharmaceutical Chemistry, Fac-
ulty of Pharmacy, Tishk International University, Iraq
Ojha, Smriti, Department of Pharmaceutical Science and Technology,
Madan Mohan Malviya University of Technology, India
Padarthi, Pavan Kumar Arya, Department of Computer Science in Artifi-
cial Intelligence and Robotics, University of Hertfordshire, United Kingdom
Pandey, Akanksha, Department of Pharmacy, School of Medical and Allied
Science, Galgotias University, India
Pingali, Sirisha, IPT, Lonza Biologics, United Kingdom
Rao, GSN Koteswara, Department of Pharmacy, School of Medical and
Allied Sciences, Galgotias University, India
Rawat, Shilpa, Department of Pharmacy, School of Medical and Allied
Science, Galgotias University, India
Saini, Manoj, Department of General Medicine, All India Institute of
Medical Science, India
Saraogi, Gaurav, Department of Pharmacy, Sri Aurobindo Institute of
Pharmacy, India
Sekar, Mahendran, Department of Pharmaceutical Chemistry, Faculty of
Pharmacy and Health Sciences, Royal College of Medicine Perak, Universiti
Kuala Lumpur, Malaysia
Sharma, Akanksha, Monad College of Pharmacy, Monad University, India
Sharma, Urvashi, Faculty of Pharmacy, Medi-Caps University, India
Singh, Aditi, Ashoka Institute of Pharmacy, Ashoka Engineering Chauraha,
India
Singh, Nishita, Madhu Vachaspati Institute of Pharmacy, India
Singh, Nitu, Faculty of Pharmacy, Oriental University, India
 List of Contributors xxix

Singh, Shilpa, Department of Pharmacy, School of Medical and Allied

Science, Galgotias University, India
Subramaniyan, Vetriselvan, Faculty of Medicine, Bioscience and Nursing,
MAHSA University, Malaysia
Sundram, Sonali, Department of Pharmacy, School of Medical and Allied
Science, Galgotias University, India
Telikicherla, Karteek, Whitbread, United Kingdom
Verma, Ashish, School of Pharmacy, Monad University, India
Verma, Poojashree, Faculty of Pharmacy, Oriental University, India
Verma, Swati, Department of Pharmacy, School of Medical & Allied
Science, Galgotias University, India
Yadav, Shalini, Dr. MC Saxena College of Pharmacy, India
 List of Abbreviations

FIR Fourth industrial revolution

ACN Australian center for nanomedicine
ADMET Absorption, distribution, metabolism, excretion,
and toxicity
AE Autoencoder
AI Artificial intelligence
AN Artificial neuron
AOUP Azienda ospedaliero-universitaria pisana
AQI Air quality index
AR Augmented reality
ASPECTS Alberta stroke program early CT score
AUC Area under the curve
BASN Body area sensor network
BBB Blood–brain barrier
BBN Bayesian belief network
BCT Blockchain technology
BE Bio equivalence
BMI Body mass index
BP Boiling point
BPNN Back propagation neural network
CAD Computer-aided diagnosis
CAD Computer-assisted detection
CAD Computer aided design
CAGR Compound annual growth rate
CAR Chimeric antigen receptor
CBI Clinical bioinformatics
CCD Charge-coupled device
CCU Critical care unit
CD Constellation of differentiation
CDMO Contract development and manufacturing
organization
CFCN FCN in a cascade

xxxi
xxxii List of Abbreviations

CGM Continuous glucose monitoring

CI Confidence interval
CNC Computer numerical control
CNN Convolutional neural network
CNS Central nervous system
CPS Cyber−physical system
CPT Current procedural terminology
CPT Common proficiency test
CPV Continuous process verification
CRNs Residual convolutional networks
CSC Chatbot-based symptom checker
CTEPH Chronic thromboembolic pulmonary
hypertension
CV Cardiovascular
CV Computer vision
CVD Cardiovascular disease
CXR Chest radiography
DApps Decentralized applications
DCNN Deep convolutional neural network
DCNs Deep convolutional networks
DDCS Decentralized data centers
DDS Drug delivery system
DFT Density functional theory
DILI Drug-induced liver injury
DL Deep learning
DLT Distributed ledger technology
DNNs Deep neural networks
DoS Denial of service
DT Decision tree
DTI Drug–target interaction
ECG Electrocardiogram
EHR Electronic health records
EMR Electronic medical records
EPA Environmental protection agency
ERPS Enterprise resource planning system
ES Expert systems
FAIR Findable, accessible, interoperable, and reusable
FDA Food and drug administration
FMA Foundational model of anatomy
 List of Abbreviations xxxiii

GAMP Good automated manufacturing processes

GANs Generative adversarial networks
GDA Gene-disease associations
GDPR General data protection regulation
GLIMS General laboratory information management
system
GMP Good manufacturing practice
GNN Graph neural networks
GP General practitioner
GPUs Graphical processing units
GRU RNN Gated recurrent units RNN
GxP Good practices
H&E Hematoxylin and Eosin
HALS Hindered amine light stabilizers
HC Hierarchical clustering
HCPCS Healthcare common procedure coding system
HDFS Hadoop distributed file system
HF Heart failure
HGP Human genome project
HIA Human intestinal absorption
HIPAA Health insurance portability and accountability
act
HIPI Hadoop image processing interface
HIV Human immuno virus
HOG Histogram of oriented gradients
HTX Hematoxylin
HVAC Heating, ventilation, and air-conditioning
I2B2 Informatics for integrating biology & the
bedside
ICD International classification of diseases
ICD-9 International classification of diseases, ninth
revision, clinical modification
ICU Intensive care unit
IHC Immunohistochemistry
IIoT Industrial internet of things
ILSC Intelligent laser speckle classification
ILSVRC ImageNet large scale visual recognition
challenge
IoS Internet of services
xxxiv List of Abbreviations

IoT Internet of things

ISO/TC 307 International organization for
standardization/technical committee 307
ISPE International society for pharmaceutical
engineering
IT Information technology
ITC Information and communication technology
ITH Intratumor heterogeneity
KNN K-nearest neighbor
LBP Local binary pattern
LgR Logistic regression
LOINC Logical observation identifiers names and codes
LPU Local processing unit
LR Linear regression
LR Logistic regression
LSTM Long short-term memory
LVO Large vessel occlusion
MAE Mean absolute error
MAM Multi-attribute monitoring
MGECNN Molecular graph encoding convolutional neural
networks
MHRA Medical products regulatory agency
MI Mutual information
MIS Medical image segmentations
MIT Massachusetts institute of technology
ML Machine learning
MLP Multilayer perceptron
MM Molecular mechanics
MNA Multilevel neighborhoods of atoms
MNT Molecular nanotechnology
MoH&FW Ministry of Health and Family Welfare
MP Melting point
MPM Medical practice management
MRI Magnetic resonance imaging
MS Mass spectrometry
MW Molecular weight
NB Naive Bayes
NDC National Drug Code
NETTAB Network tools and applications in biology
 List of Abbreviations xxxv

NFC Near field communication

NHCAA National Health Care Anti-Fraud Association
NLP Natural language processing
NMEs New molecular entities
NMSC Nonmelanoma and melanoma skin cancer
screening techniques
NS Network structures
NSCLC Non-small cell lung cancer
NSCLC Non-small cell lung carcinoma
OEE Overall equipment effectiveness
ORB Oriented FAST and rotated BRIEF
OT Operational technology
PAI Pre-approval inspections
PAT Process analytics technology
PC Personal computer
PCA Principal component analysis
PCPs Primary care providers
PDA Personal digital assistance
P-gp P-glycoprotein
PHI Protected health information
PHR Personal health record
PI Pharmaceutical industry
PLS Partial least squares
PMS Patient management system
PMS Patient monitoring system
PMS Practice management system
PNN Probabilistic neural networks
PPB Plasma protein binding
PR Paper record
pRAS Psoriasis risk assessment systems
PTLR Plain thoracolumbar radiography
PWDs Person with diabetes
QA Quality assurance
QC Quality control
QR Quick response
QSAR Quantitative structure-activity relationship
R&D Research and development
RASAR Read across structure-activity relationship
RBM Restricted Boltzmann machine
xxxvi List of Abbreviations

RECIST Response evaluation criteria in solid tumors

RF Random forest
RFID Radio frequency identification
RFL Random forest learning
RNN Recurrent neural networks
ROI Region of Interest
RPA Robotic process automation
RPET Recycled polyethylene terephthalate
RPM Remote patient monitoring
SC Smart contract
SGDClassifier Stochastic gradient descent classifier
SIG Special Interest Group
SMILES Simplified molecular-input line-entry system
SNGP Spectral-normalized neural Gaussian processes
SNOMED-CT Systemized nomenclature of medicine – clinical
terms
SSS Safe, secure, and scalable
STE Speckle-tracking echocardiography
SVM Support-vector machine
SWOT Strength, weakness, opportunity, and threat
TB Tuberculosis
TBI Translational bioinformatics
TDM Typical drug makers
TM Template matching
TPI Terahertz pulsed imaging
TTD Therapeutic target database
UCSF University of california at san francisco
UM Universal marker
UMA Un-mixing algorithm
UQ Uncertainty quantification
VAEs Variational autoencoders
VDA Variant disease associations
VDF Van de Graaff factor
VF Vertebral fracture
VR Virtual reality
WDs Wristwatches
WHO World health organization
ZRSS Zenith robotic surgical method
 1
Digitalization in the Pharmaceutical
Industry: Prioritization Throughout the
Digital Transformation

Sudhanshu Mishra1* , Shalini Yadav2 , Nishita Singh3 , Rajiv Dahiya4 ,

Swati Verma5 , and Shivendra Mani Tripathi1
1 Department of Pharmaceutical Science & Technology, Madan Mohan
Malaviya University of Technology, India
2 Dr. MC Saxena College of Pharmacy, India
3 Madhu Vachaspati Institute of Pharmacy, India
4 School of Pharmacy, Faculty of Medical Sciences, The University of the

West Indies, Trinidad & Tobago

5 Department of Pharmacy, School of Medical & Allied Science,

Galgotias University, India

*Corresponding author: Department of Pharmaceutical Science & Technol-
ogy, Madan Mohan Malaviya University of Technology, Gorakhpur, Email:
[email protected], Contact: +91-8377836989.

Abstract
The development of a manufacturing industry’s production process is impos-
sible without including digitalization. Automated and computerized pro-
cesses are part of digitalization, which results in cost savings as well as
increased accuracy and efficiency. Due to a lack of training and a wide
range of research and manufacturing procedures, the pharmaceutical industry
(PI) has been a staunch opponent of digitalization. Traditional and new
pharmaceuticals are becoming more popular, so there’s little doubt that PI will
need to be digitized. Because of this, contract development manufacturing
organizations have specific problems when it comes to implementing new
technologies. GMP should be closely linked to PI digitalization and CDMO in
particular, and success in PI digitalization demands a constant focus on GMP.

1
2 Digitalization in the Pharmaceutical Industry: Prioritization Throughout

Another key part of CDMO digitalization is ensuring that the company’s

stakeholders are kept up to date on the company’s progress. This article
will talk about the benefits and drawbacks of digitizing CDMOs, focusing
on practical ways to keep going digital.

Keywords: Digitalization and process improvements, pharmaceutical indus-

try, GMP, contract development manufacturing organization.

1.1 Introduction
By 2020, pharmaceutical business is expected to produce $122.845 billion in
global revenues, making it the top-most fastest-expanding financial sector.
Since 2017, the pharmaceutical industry has expanded at an annual rate
of 5.9%. By 2017, the pharmaceutical business earned $1.143 billion in
sales and is predicted to generate $1.462 billion by 2021. The utilization of
information from systems integration and linked devices to better recognize
and assess consumer wants and improve supply chain performance is referred
to as “digitalization.” In the future, pharmaceutical Industry business 4.1 will
offer intelligent automation technologies and may help enhance production,
for instance, tailored medication, additive manufacturing, and localized 3D
printing of therapy. Digitalization technology is now more crucial than ever
in enabling companies of all sizes to enhance their performance by rais-
ing manufacturing efficiency, enhancing competitive capabilities, improving
budgeting, scheduling accuracy, and ensuring financial sustainability [1].
Old product-oriented business models are under strain because of variables
such as patent expirations, greater customer demand, more competition, and
increased pricing pressures. It is no secret that digital transformation is
currently reshaping industries as digital services other than products become
increasingly ubiquitous. According to digitalization and “connected health,”
the “triple goal” of enhancing treatment, improving quality of care, expanding
access to care, and lowering per capita costs may all be accomplished through
“connected health” [2, 3]. This industry is known for its high profitability
and low risk, as well as its extensive and expensive R&D periods and
intense marketing. Computer modeling can assist in cutting costs in the
pharmaceutical industry, where production interruptions and digitalization
are typical [4, 5]. Through the Internet of Things, machine-to-machine
connectivity and machine learning artificial intelligence [6] provide fric-
tionless operations, automated remedial actions, and predictive maintenance.
Small mistakes in the pharmaceutical manufacturing environment can have
 1.2 Good Manufacturing Practice (GMP) within Pharmaceuticals 3

life-changing consequences for patients as well as substantial financial, legal,

and reputational consequences for the corporation [7].
In the PI, digitalization can benefit both small and large firms [8].
Manufacturers may be able to maintain quality while also complying with
upcoming serialization standards if the serial numbers of the supply chain
are used by the manufacturers to digitalize medications that are bogus-proof.
Digitalization can be the topmost way to meet the demand of pharmaceuti-
cal businesses rising from global markets [9, 10]. Using automated sensor
technologies, social networking sites, and health applications, it is also fea-
sible to track medication compliance and predict demand across areas [11].
Cloud-based information exchanges may be used to stay in compliance with
laws, discover manufacturing proficiencies to save money, and engage with
suppliers and distributors more promptly.
Digitalization technologies must be employed to deploy PI. Digitalization
is critical if medical items are to fulfill the ever-increasing demand of a
changing world and people. PI has been active in digitalization for a longer
length of time and with less success than other industries. As a result, the
purpose of this research is to look into the notions of successful digitalization
and how they might be used for PI. This article focuses on contract develop-
ment and manufacturing organizations (CDMOs). Because GMP is such an
important component of industrial digitalization, general aspects of GMP in
PI are also investigated and discussed. It is mostly a review article on Good
Manufacturing Practices and processes that are crucial to the digitalization of
the pharmaceutical sector. Because this is an introductory post, we won’t go
to great length regarding various technologies.

1.2 Good Manufacturing Practice (GMP) within

Pharmaceuticals
Regulations all around the globe use GMP, or “Good Manufacturing Prac-
tices,” to keep tabs on the approval and licensing of new products [12].
Additional safeguards can be taken to guarantee the safety and efficacy of
pharmaceuticals and medical equipment, as well as food and plasma, under
these laws. A quality-oriented approach to production is necessitated by GMP
rules, allowing organizations to avoid or eradicate errors and inaccuracies.
Thus, the buyer is shielded against receiving substandard or even hazardous
products [13]. Other quality-based operations controls, such as accurate
screening and high-quality raw materials, recognition, and deviation inves-
tigation, are included in GMP systems. GMP regulations include everything
from records management to employee certifications to sanitation, apparatus
certification, cleanliness, and process validation [14].
4 Digitalization in the Pharmaceutical Industry: Prioritization Throughout

1.2.1 Enforcement of GMP

Even if a pharmaceutical manufacturer is situated in another nation, GMP
must be followed for their goods to be sold in the European Union. In the
United Kingdom, GMP inspections are overseen by the Medical Products
Regulatory Agency (MHRA), whereas in Canada, GMP inspections are over-
seen by the Health Product and Food Branch Inspectorate. Day-to-day assess-
ments are carried out by each appointed officer to verify that medications are
manufactured correctly and safely according to GMP guidelines. The FDA
has recently begun inspecting Chinese pharmaceutical manufacturing plants
to check that GMP rules are being followed [15, 16]. Several countries around
the world conduct GMP inspections regularly to ensure that medications are
manufactured in a contaminant- and error-free environment. Before allowing
new pharmaceuticals to be commercialized, several nations conduct GMP
compliance checks as part of pre-approval inspections (PAI). Because this is
an introduction post, we will focus on illustrious technology [17, 18].
It is believed by the PI that a primary goal of GMP is risk reduction in
pharmaceutical manufacturing, as this cannot be accomplished by analysis of
the final product. Mistakes in packaging or labeling can result in patients
receiving the wrong medication as well as unanticipated and unwelcome
product contamination and too much or too little of a component [19]. There
are many different types of pharmaceutical manufacturing processes that are
covered by GMP [20, 21]. This includes everything from raw materials and
infrastructure to training and cleanliness.
Based on the kind of GMP violation and pharmaceuticals implicated,
penalties might vary. There’s little likelihood that a pharmaceutical that has
been prepared in violation of GMP would be hazardous or ineffective. As a
result, healthcare providers will be better equipped to consider the advantages
and disadvantages of various treatment options for their patients because of
the FDA and maybe other regulatory bodies issuing guidance that is more
contextually relevant.

1.2.2 The pharmaceutical industry’s five GMP principles

Product safety and high quality are two of the primary concerns for the PI,
and the five GMP principles (5Ps) address each of these concerns. The GMP
5Ps is a useful framework for thinking about the most important aspects
of compliance. People, Processes, Procedures, Premises, Equipment, and
Products comprise the GMP’s five Ps. To comply with GMP, the industry
generally agrees that these five criteria must be prioritized [23, 24]. These
 1.2 Good Manufacturing Practice (GMP) within Pharmaceuticals 5

Figure 1.1 Schematic representation of 5Ps of GMP.

five principles are essential to any discussion about best practices. When
it comes to pharmaceutical product production, GMP is designed to help
keep risks to a minimum, especially those that can’t be prevented once the
final pills have been consumed. The pharmaceutical sector and businesses
that produce consumables are heavily influenced by GMP and the 5Ps. A
schematic representation of the GMP 5Ps is shown in Figure 1.1, with more
information provided below.

1.2.2.1 People
Every person involved in the pharmaceutical production process must be
made aware of their responsibilities and obligations. The approach requires
employees to be trained and their performance to be assessed. To maintain
their effectiveness in ensuring that their staff is adequately trained and com-
petent, manufacturers must evaluate their training methodologies regularly.
A manufacturing company is nothing without the people who run it. That
is why it is so important. Employees must be trained in how to achieve
the desired results. To increase productivity and efficiency, roles and duties
are distributed among workers. Depending on their talents, competencies,
and experience, each employee is given a unique assignment. When we
say “written documentation and monitoring,” we mean timely reporting of
deviations from protocols and any other important aspects that need to be
tracked. Because of this, all employees should be able to see and understand
the processes that are in place. Regular reviews of employees must be con-
ducted to make certain that they are in the wake of established procedures and
meeting the company’s requirements. To ensure product safety and decrease
6 Digitalization in the Pharmaceutical Industry: Prioritization Throughout

the risk of contamination, these quick inspections need to be implemented.

Early detection of any inconsistencies is good for businesses, even if the
requirements and methods aren’t the same.
1.2.2.2 Procedures
An instruction manual is a set of guidelines for ensuring that a technique or a
part of a process is carried out consistently. To keep things running properly,
every employee in an industrial organization must adhere to the regulations
and processes in place [25]. Regular data collection at important phases of
production will make it simpler to establish the cause of any quality issue if
a group looks to have a problem that must be canceled [26]. To ensure that a
company’s activities meet the required standards, both processes and proce-
dures must be developed and documented. It is imperative that all procedures
are well stated and adhered to. Disturbances from the predetermined routine
must be properly investigated.
1.2.2.3 Process
A process is a series of linked operations that convert inputs to outputs. It
is a collection of well-organized tasks that must be followed precisely to get
maximum production and rewards. Different techniques and activities may
be used to speed up the manufacturing process, allowing for the creation of
a bigger quantity of goods in a shorter amount of time. However, extensive
investigations and inspections of the credibility and potential of newly chosen
tactics in this respect should be conducted early on to ensure that quality is
not compromised.
1.2.2.4 Premises and equipment
In contrast to “equipment,” which refers to machines and healthcare appli-
ances that are accustomed to monitoring, curing, or preventing an individual’s
health or ailments, “premises” refers to any structure, building as well as any
equipment or apparatus physically attached or incorporated into the building
frame. Every effort should be made by manufacturing companies to construct
their facilities and equipment so that they can be cleaned effectively and
cross-contaminated. The location, design, construction, maintenance, and
modification of the facility should be tailored to the specific needs of the
business [27].
Documentation of cleaning procedures for every facility and piece of
equipment must be kept. Protocols for preventing cross-contamination and
documented calibration instructions must be in place [28]. To make sure that
a facility’s equipment is performing as intended and producing consistent
1.3 Traditional Drug Production vs. Contract Development and Manufacturing 7

results, these requirements must be taken into account during the construc-
tion process. In addition to routine equipment and machinery inspections,
sanitation checks are required [29]. Equipment must be cleaned, dried, and
washed regularly to ensure that it does not damage anything.

1.2.2.5 Products
There are several ways to increase the quality and consistency of items
that customers will use. Ensure that all commodities enter and depart the
facility in excellent shape; it is also an end-to-end responsibility [30]. When
it comes to raw materials and components, manufacturers, for example,
need to set standards. Repetitive processes are essential for all stages of
R&D: processing, monitoring, manufacturing, testing, sampling, packing,
and record keeping. In the context of a manufacturing company, this conveys
the magnitude of the issue they are trying to solve. As a result, research
was conducted, and resources such as manpower, money, and other materials
were allocated [31]. An organization’s inability to provide products that meet
the needs of its customers is an extremely significant threat to its long-term
viability and integrity [32]. As a result, there is a significant demand for
assets, intermediates, components, and final goods. For production, packag-
ing, sampling, testing, archiving stability data, and monitoring status, look for
the most efficient, hygienic techniques [33].
It is possible to limit the probability of cross-contamination and mistakes
in the manufacturing of medicines and other consumables if the 5 Ps are
handled appropriately. Making sure that the necessary ingredients are in
the right proportions for the intended effect is dependent on a consistent
pharmaceutical production strategy and technology. Quality cannot be “tested
into” drugs retrospectively, as we are constantly told. Instead, the only way to
achieve precision and dependability in large-scale medication manufacturing
is to adhere to set criteria by appropriately educated and accountable people
[34, 35]. That is why it is important to keep the GMP 5 Ps in mind while
implementing digitalization procedures.

1.3 Traditional Drug Production vs. Contract Development

and Manufacturing Organizations
Drug development and manufacturing services are provided by CDMOs,
which are corporations that have a contract with pharmaceutical firms. Out-
sourcing drug development and production is a common practice among
8 Digitalization in the Pharmaceutical Industry: Prioritization Throughout

CDMOs and pharmaceutical companies. All customer’s demands are taken

into consideration. For pre-clinical, Phase I, and late-stage clinical trials,
materials for formal stability and scale-up, commercial manufacturing, batch
registrations, serialization, and shipment are all part of CDMO services.
Developing and executing GMP and digitalization processes must take
CDMOs’ variations from conventional drug manufacturers into account.
Subsequent sections cover some of these subjects in greater depth. It provides
a comprehensive array of services. CDMOs have a far broader range of
experience and competence than typical drug makers (TDM). Large CDMOs
also spend heavily on equipment. According to TDM, internal drug design
and manufacturing present challenges for pharmaceutical businesses, whether
they are looking to expand capacity, introduce a new medication, or change
the frequency at which they manufacture [36].
On the other hand, businesses that outsource to a CDMO get access to
a vast array of equipment and facilities without having to pay ownership
expenses. Also recognized for helping pharmaceutical companies scale up,
CDMOs are well-positioned to assist with this process as well. Pharma-
ceutical firms may be put in jeopardy if production volumes are altered
or a new medicine type is introduced. Working with a CDMO reduces
the risk and length of time involved in making these kinds of decisions.
Companies of all sizes have the opportunity to flourish thanks to outsourcing
pharmaceutical development and manufacturing. They can operate lean and
efficient operations since they know that medication development and man-
ufacturing will not cost a lot of money for pharmaceutical businesses of all
sizes [37].

1.4 Digitalization of CDMO

Digital transformation plans, high levels of digital diffusion, and staff
upskilling should all result in the projected productivity improvement. It has
never been a better time for businesses of all sizes to embrace digitalization,
since our economic well-being depends on it, of course. Cybersecurity, artifi-
cial intelligence, and other activities will be necessary for your organization
to undertake as part of the digitalization and digital transformation process.
You’ll need a current skill set to keep up with these new technologies and put
them to good use as soon as they arrive. You may significantly improve your
game by learning new skills and going to training sessions. All businesses,
not just a select few, must embrace digitalization and technology to increase
productivity.
 1.5 Opportunities 9

Figure 1.2 Opportunities and challenges of digitalization.

The digital revolution will hurt businesses that do not adopt new tech-
nologies. As a result of the consequences, these firms may be left behind.
There must be a real digitalization of all businesses and organizations to
have a substantial influence. So, big corporations need to face their technical
demons and design a strategy to overcome their adoption obstacles. Small
and medium-sized businesses need to start integrating technology to remain
competitive. Digital transformation of business models and the whole indus-
try and value chain will need a productivity strategy for companies. There
is an overarching digital transformation strategy behind every major reform,
training program, and digitalization effort.
Organizations face both possibilities and problems when it comes to
dealing with change. As the most difficult issue, and maybe the most common
error, managers regard change as a short-term phenomenon. Change is a
continuous process, not a one-time event, in any business. A company’s long-
term success depends on its ability to deal with and negotiate with these issues
on an ongoing basis [37, 38]. The digitalization process necessitates regular
updates to services, procedures, and ways of operation. Also, there are both
advantages and disadvantages to it. It is vital to anticipate and prepare for
obstacles to deal with them successfully. Figure 1.2 shows pros and cons of
digitalization.

1.5 Opportunities
Organizations face both possibilities and problems when it comes to dealing
with change. As the most difficult issue, and maybe the most common error,
10 Digitalization in the Pharmaceutical Industry: Prioritization Throughout

managers regard change as a short-term phenomenon. Change is a continuous

process, not a one-time event, in any business. A company’s long-term suc-
cess depends on its ability to deal with and negotiate with these issues on an
ongoing basis. The digitalization process necessitates regular updates to ser-
vices, procedures, and ways of operation. Also, there are both advantages and
disadvantages to it. It is vital to anticipate and prepare for obstacles to deal
with them successfully. As a result, digitalization’s pros and downsides are
examined. The fear that robots will replace workers is a common occurrence
in the industrial sector, but the focus should instead be on how individuals and
machines can work together to generate the best results possible. You can get
the most out of your smart factory’s production processes and labeling if your
employees are more tech-friendly. Human–computer symbiosis is the basis
of human–machine interaction. A project should be started to see if machines
and software can boost system productivity in ways that are more intelligent
and physical than either human or machine productivity alone.
Pharmaceutical companies must adhere to exacting standards and laws
and safeguard their data with great care. These companies might benefit
from finding a strategy that is both reliable and efficient. Industrial processes
may be monitored, regulated, and optimized with the aid of a digitalization
plan, resulting in increased productivity and efficiency. The use of GMP
digitalization may improve several business components, as will be shown
in the following paragraphs.

1.5.1 To put it another way, productivity

In recent years, pharmaceutical manufacturing has expanded its global reach.
The demand for both national and imported goods will be at its peak with
the mere expansion in the sector of healthcare, economics, and insurance.
Demand for pharmaceuticals is rising along with the variety of pharma-
ceutical needs as emerging nations battle noncommunicable illnesses that
are more prevalent in wealthy countries. AIDS, malaria, and tuberculosis
are just a few of the infectious diseases that continue to wreak havoc in
many underdeveloped nations. In addition, as individuals live longer, the
worldwide population of adults aged 65 and older is expected to expand. It is
also important that the product can be produced in large enough quantities
and quickly enough to meet these requirements throughout time. This is
especially true in the PI, where the medicine is often lifesaving and requires
constant access. These challenges in the industrial sector necessitate a new set
of tactics to deal with them. Through the use of digitalization, new and more
 1.5 Opportunities 11

effective ways to fulfill increased production demand may be found through

the use of digitalization, which improves manufacturing processes and speeds
them up while maintaining product quality.

1.5.2 The product’s quality

Pharmaceutical companies must collect operational data to ensure the quality
of their products. On the other hand, many firms are still using paper-based
systems, which increases the likelihood of human error in data collection
and management. As a result, it is more difficult to absorb this information
in written form. By reducing human errors and enhancing data collection
efficiency, digitalization technology can help decrease data entry errors. For
example, pharmaceutical companies may use digitalization methods such
as machine learning to acquire, standardize, and analyze data from many
sources. When a batch is finished, basic quality assurance reports are imme-
diately available [37, 38]. To sum up, digitalization has the potential to
increase quality control’s efficiency and reliability. Early batch results are
now available during the completion of the manufacturing process by the
application of digitalization [39].

1.5.3 Control
The quality control standards at the PI are among the most demanding in
the industry. From product development through packaging and labeling to
equipment cleaning, every step in the process must be strictly controlled.
The pharmaceutical industry frequently employs the batch process, in which
products are manufactured in batches rather than continually. One disad-
vantage is that even a minor mistake might ruin an entire batch. Negative
consequences can include serious bodily injury, penalties, and litigation, as
well as a considerable loss of reputation if a defective batch is not discovered
by the manufacturer in time.
Effective batch control is needed to avoid these and other potentially
harmful outcomes. Digitalization makes it possible to better manage the
process and boost output in this case [40]. Digitalization can also assist
you in streamlining your production’s packaging phase. It’s easier to find
methods to improve your packaging process when it’s managed, monitored,
and visualized in the same manner that batch manufacturing can be. You
may also monitor and oversee your business from any location by accessing
data remotely. The pharmaceutical industry’s profitability relies heavily on
the digitalization of control tasks. Profitability is immediately increased by
12 Digitalization in the Pharmaceutical Industry: Prioritization Throughout

reducing the consumption of raw materials, human resources, and time, as

well as reducing the risk of low-quality final products because of digitally
automated control systems [40].

1.5.4 Cost-effectiveness
Efficiency may be described as the time, money, and resources needed by
a business to produce a specific amount of output. As a result, productivity
and efficiency are inseparably linked. As a result of digitalization, you’ll be
able to get a complete picture of your operating efficiency. The data and
reports you collect can be used to pinpoint areas in which your procedures
and infrastructure need to be enhanced. Your organization can also use it
to automate some processes. If you use digitalization, you can do the same
amount of work with less time, effort, and resources. With real-time alerts,
for example, operators can reply quickly with automated warnings [41, 42].
The pharmaceutical industry relies heavily on validation due to the stringent
rules and regulations that must be followed. In this industry, digitalization
also contributes to efficiency [43]. You don’t have to review or update your
processes before you can change or enhance them, which saves you time and
money [43].

1.6 Challenges
Supply chain and operational improvements for pharmaceutical firms face
several challenges. Because of the quick rate of technological change, they
must work with a wide range of external partners throughout the supply chain
to find solutions [44]. To overcome long-standing working patterns and the
resistance of organizations and employees used to decades-old procedures,
businesses will have to be exceedingly transparent. Additionally, there’s a lot
of hype and possible dangers to be aware of [45]. There are various crucial
success factors on this journey. As a starting point, enterprises should famil-
iarize themselves thoroughly with the ecosystem and the rapidly evolving
technology inside it. Companies in the pharmaceutical industry must also
have the appropriate resources, such as a diverse team of specialists and
investment funds, to be successful. The supply chain must be completely
connected, and players must work with their partners to do so.
For the most part, companies must recognize that this is a process
that requires choosing a few activities, adopting an experimental mentality,
and learning by doing. The pharmaceutical industry will also face several
 1.7 Execution of the Digital Transformation 13

important challenges. Cybersecurity is one of the most pressing issues in

digital operations [46, 47].

1.7 Execution of the Digital Transformation

The pharmaceutical industry will be affected by technological advancements.
Because of the digitalization of industrial production, the manufacturing
process may be more self-organized, and useful data can be collected [48].
This is made possible by current information and communication technology.
Preparing for the future requires pharmaceutical and biotech firms to take into
consideration technological advancements such as digitalization [36]. A good
illustration of this is the need for CDMOs to stay on top of these changes.
When they get involved early in the process, they have the opportunity to
become a valuable partner for their consumers. The following criteria and
aspects must be addressed to achieve a successful implementation as outlined
in the next paragraphs.

1.7.1 Focus on value

Digitalization is a term that encompasses a broad range of data in CDMOs.
Data analytics software in R&D, for example, is not linked to the value chain.
It is necessary to categorize digitalization to have a clear view of the problem.
When it comes to digitalization at a visual inspection workstation, it is like
switching from a paper book to a tablet. Employees would instead utilize a
tablet to submit the findings of their inspections into the Enterprise Resource
Planning System (ERPS). A more complex solution, such as integrating
formerly paper-based duties into the new application, is also possible [49].
Using analog to digital data transmission in a laboratory, for example, may
be linked. Measurement equipment data would be automatically sent to the
software, where it would be stored and processed for future use. Digitalization
has led to several new trends and technologies, including machine learning,
artificial intelligence, blockchain, and big data. Despite their immense poten-
tial, these technologies should only be used when necessary [50]. Projects
should be chosen based on whether or not they will improve efficiency
and effectiveness and thus add value to the company and its all-important
partners, such as customers and suppliers, rather than on how often and how
many times they happen. The pharmaceutical industry will be affected by
technological advancements. Because of the digitalization of industrial pro-
duction, the manufacturing process may be more self-organized, and useful
14 Digitalization in the Pharmaceutical Industry: Prioritization Throughout

data can be collected [48]. This is made possible by current information and
communication technology. Preparing for the future requires pharmaceutical
and biotech firms to take into account technological advancements such as
digitalization [36]. A good illustration of this is the need for CDMOs to
stay on top of these changes. When they get involved early in the process,
they have the opportunity to become a valuable partner for their consumers.
The following criteria and aspects must be addressed to achieve a successful
implementation as outlined in the next paragraphs.

1.7.2 Holding the adaptability

While standardization can assist a CDMO in minimizing the complexity of its
entire operation, flexibility is required to meet the demands of varied clients.
It is possible to adjust paper-based procedures to handle numerous filling
techniques depending on the customer’s requirements. As an alternative, a
digital system may limit flexibility by standardizing procedures so that they
can be managed by the system [49]. In their manufacturing requirements,
clients of a CDMO, for example, may use a variety of terminologies. If
they are not standardized, different wordings lead to a plethora of process
variances that must be documented digitally. Uniformity and flexibility can
be achieved by using pre-programmed text modules with all the essential
components. CDMOs can stay adaptable even if they are digitalized, but it
is important to keep this in mind while designing systems [51].

1.7.3 Prioritize the quality

In the world of high-priced injectables, the first and most important need is
quality. As a result, patients are getting the same medications that CDMOs
produce for their pharmaceutical and biotechnology clients. Because pharma
digitalization boosts productivity while simultaneously enhancing safety and
convenience, one way to get there is to focus on the global supply chain up to
implementation and contemplate several single pharmaceutical manufactur-
ing stages overall. However, digitalization will not be completed linearly and
must instead be tackled as a comprehensive program. As a result of several
subprojects, the phases of the process inside an organization become increas-
ingly intertwined. Pharmaceutical companies, in particular, are particularly
hard hit by this. To ensure compliance with regulations, even minor changes
in procedures must be taken into consideration. The quality and efficiency of
these operations can always be better, even if they are done well.
 1.7 Execution of the Digital Transformation 15

1.7.4 Standardization of process

In the world of high-priced injectables, the first and most important need is
quality. As a result, patients are getting the same medications that CDMOs
produce for their pharmaceutical and biotechnological clients. Because
pharma digitalization boosts productivity while simultaneously enhancing
safety and convenience, one way to get there is to focus on the global supply
chain up to implementation and contemplate several single pharmaceutical
manufacturing stages overall. However, digitalization will not be completed
linearly and must instead be tackled as a comprehensive program. As a
result of several subprojects, the phases of the process inside an organization
become increasingly intertwined. Pharmaceutical companies, in particular,
are particularly hard hit by this. To ensure compliance with regulations, even
minor changes in procedures must be taken into consideration. Even if they
are done well, the quality and efficiency of these operations can always be
improved. Digitalization in the pharmaceutical industry has the potential to
improve both the security and the efficiency of documentation processes. By
definition, CDMOs are separate from their biopharmaceutical customers, and
these distinctions may become more apparent as digitalization takes hold. The
utilization of laboratory testing equipment is one example. Laboratory testing
equipment is determined by customers, not CDMOs [52].
In the wake of the wide range of testing approaches, net connectivity
and execution of processes over the digital platform have become more
challenging. As a consequence of the wide variety of goods and services
that CDMOs provide, they often have to employ a wide variety of process
variations, including a wide range of documentation techniques. Attempting
to implement all of these paper-based documentation methods into the digital
system at once would result in a major loss of system reliability and effi-
ciency. As a result, harmonizing and standardizing procedures is essential
before using software to digitalize activities. In most cases, digitalization
is not completed in a single effort. Instead, it’s considered a multi-project,
all-encompassing initiative. Interdependence and operational linkages are
common among these smaller initiatives. So, it is important to identify the
presence of any synergies or project dependencies. Even more difficult than
one may think is defining who controls the corporate practices. Therefore, it
is important to figure out what cross-divisional responsibilities there are and
who is in charge of them to digitize operations [53].
16 Digitalization in the Pharmaceutical Industry: Prioritization Throughout

1.7.5 An illustration of digitalization

There is a slew of extra-legal and administrative hurdles to jump over
first. Following the production process, every filled item procured by the
client is subjected to a final graphical examination. The aseptically prefilled
cartridges, vials, and syringes are subjected to an independent quality exami-
nation after compounding and filling and before packaging. For illustration’s
sake, consider the Vetter Pharma Corporation. The inspection reports con-
taining all the findings were reported before the introduction of the System
Application and Products system. There are around 60,000 manufacturing
standards that SAP produces each year for use by the Visual Inspection team.
It was then the shift coordinator’s responsibility to manually enter the results
into the SAP software systems and batch analysis. When it comes to adopting
and implementing digitalization, employees can be classified as either digital
or non-digital natives. This includes management, employees who will be
touched by this new policy, and their union representatives, as well as those
who support or oppose it. Any time soon is better than never when it comes
to setting up a dedicated transformation team [54].

1.8 Conclusions
In today’s technological, industrial, and economic climate, the digitalization
of manufacturing processes is universally accepted as essential. Because of
this, pharmaceutical sector digitalization is being held back by the resistance
of PI, which has led to delayed progress. Lower prices, improved quality, and
reduced capacity restrictions are some of the advantages of digitalization in
PI. For the most part, pharmaceutical businesses have been loath to utilize
arithmetical manufacturing methods because they think their systems, data,
and employees are not ready for it now. However, many firms have realized
that waiting is no longer an option and have begun to experiment with
digitalization. Using a digital platform has various advantages, including
the ability to track multiple manufacturing components, collect data, and
discuss experiment findings in real-time. When it comes to digitalization,
pharmaceutical companies and CDMOs have a lot in common. Commodities
and operations of a CDMO can be improved through digitalization if done
effectively. Digitalization in the pharmaceutical sector can enhance product
and process quality when implemented correctly. This involves dealing with
complexity while being adaptable for our customers, providing a smooth-
out modification for all employees, and improving the whole value chain for
 References 17

CDMOs. To improve pharmaceutical development, contemporary CDMOs

may establish stronger personal relationships with the many professions they
serve by centralizing all of their services.

Acknowledgments
I’d like to express my gratitude to my co-authors for their contributions of
expertise and effort, as well as their participation in compiling the work.

Conflicts of Interest
There are no conflicts of interest declared by the authors.

Funding
No funding required

References
[1] Faraj, S., Renno, W., & Bhardwaj, A. (2021). Unto the breach: What
the COVID-19 pandemic exposes about digitalization. Information and
Organization, 31(1), 100337. DOI: 10.1016/j.infoandorg.2021.100337
[2] Iglehart, J. K. (2014). Connected health: emerging disruptive technolo-
gies. health affairs, 33(2), 190-190. DOI: 10.1377/hlthaff.2014.0042
[3] Fecha, P. M. S. (2017). The Return of the Investment of the Digital Chan-
nels in Pharmaceutical Industry (Doctoral dissertation, Universidade de
Coimbra).
[4] Schaufelberger, D. E., Koleck, M. P., Beutler, J. A., Vatakis, A. M.,
Alvarado, A. B., Andrews, P., ... & Forenza, S. (1991). The large-scale
isolation of bryostatin 1 from Bugula neritina following current good
manufacturing practices. Journal of natural products, 54(5), 1265-1270.
DOI: 10.1021/np50077a004
[5] Anthony Jnr, B., & Abbas Petersen, S. (2021). Examining the digitalisa-
tion of virtual enterprises amidst the COVID-19 pandemic: a systematic
and meta-analysis. Enterprise Information Systems, 15(5), 617-650.
DOI: https://doi.org/10.1080/17517575.2020.1829075
[6] Ngamvichaikit, A. (2021). Leveraging design thinking for pharma-
ceutical digital marketing. Asian J. Business Res, 2021, 11. DOI:
10.14707/ajbr.210102
18 Digitalization in the Pharmaceutical Industry: Prioritization Throughout

[7] Sehlstedt, U., Bohlin, N., de Maré, F., & Beetz, R. (2016).
Embracing digital health in the pharmaceutical industry. Interna-
tional Journal of Healthcare Management, 9(3), 145-148. DOI:
https://doi.org/10.1080/20479700.2016.1197513
[8] Lakshmi, B., & Patel, S. (2020). Digital Marketing in Pharmaceutical
Industry–An Overview and Assessment.
[9] Lakshmi, B., & Patel, S. (2020). Digital Marketing in Pharmaceutical
Industry–An Overview and Assessment.
[10] Rosenbaum, M. S., Ramírez, G. C., Edwards, K., Kim, J., Campbell,
J. M., & Bickle, M. C. (2017). The digitization of health care retail-
ing. Journal of Research in Interactive Marketing. DOI: 10.1108/JRIM-
07-2017-0058
[11] van Velthoven, M. H., Cordon, C., & Challagalla, G. (2019). Digitization
of healthcare organizations: the digital health landscape and information
theory. International journal of medical informatics, 124, 49-57. DOI:
10.1016/j.ijmedinf.2019.01.007
[12] Cramer, M. M. (2006). Food plant sanitation: design, main-
tenance, and good manufacturing practices. CRC Press. DOI:
https://doi.org/10.1201/9781420005943
[13] Patel, K. T., & Chotai, N. P. (2011). Documentation and records: harmo-
nized GMP requirements. Journal of young pharmacists, 3(2), 138-150.
DOI: 10.4103/0975-1483.80303
[14] Patel, K. T., & Chotai, N. P. (2008). Pharmaceutical GMP: past, present,
and future–a review. Die Pharmazie-An International Journal of Phar-
maceutical Sciences, 63(4), 251-255. DOI: 10.1691/ph.2008.7319
[15] World Health Organization. (2007). WHO guidelines on good manufac-
turing practices (GMP) for herbal medicines. World Health Organiza-
tion.
[16] Harris, J., & Hill, R. (2010, April). Building a trusted image for embed-
ded systems. In Proceedings of the Sixth Annual Workshop on Cyber
Security and Information Intelligence Research (pp. 1-4).
[17] Rangarajan, A. (2015). The FDA and Worldwide Current Good
Manufacturing Practices and Quality System Requirements: Guide-
book for Finished Pharmaceuticals. Quality Progress, 48(4), 60.
https://asq.org/quality-press/display-item?item=H1458
[18] Haleem, R. M., Salem, M. Y., Fatahallah, F. A., & Abdelfat-
tah, L. E. (2015). Quality in the pharmaceutical industry–A lit-
erature review. Saudi pharmaceutical journal, 23(5), 463-469.
DOI: 10.1016/j.jsps.2013.11.004
 References 19

[19] Abhinaya, N., Thunga, G., Muddukrishna, B. S., Pai, R., Shenoy, U.
R., Khan, S., & Pai, K. G. (2019). Research on effective manage-
ment of manufacturing defects to avoid product recalls: a challenge to
pharmaceutical industry. Research Journal of Pharmacy and Technol-
ogy, 12(12), 6124-6132. DOI: 10.5958/0974-360X.2019.01064.3
[20] Abou-El-Enein, M., Römhild, A., Kaiser, D., Beier, C., Bauer, G., Volk,
H. D., & Reinke, P. (2013). Good Manufacturing Practices (GMP)
manufacturing of advanced therapy medicinal products: a novel tailored
model for optimizing performance and estimating costs. Cytother-
apy, 15(3), 362-383. DOI: 10.1016/j.jcyt.2012.09.006
[21] Taylor, P. (2008). Pharmaceutical excipients: where now for GMP. RAJ
Pharma, 19(12), 815-818. DOI: 10.1007/s40005-017-0354-4
[22] Kumar, N., & Jha, A. (2019). Application of principles of supply chain
management to the pharmaceutical good transportation practices. Inter-
national Journal of Pharmaceutical and Healthcare Marketing. DOI:
10.1108/IJPHM-09-2017-0048
[23] George, B. V. C. D. (2012). Improvement of manufacturing operations at
a pharmaceutical company. A lean manufacturing approaches. J. Manuf.
Technol. Manag, 23(1), 56-75. DOI: https://doi.org/10.5772/59027
[24] Lee, F. S., Wang, X., & Fu, P. P. (2010). Quality assurance and safety
protection of traditional Chinese herbs as dietary supplements. Funct.
Foods East, 431. DOI: 10.1080/10590500902885676
[25] Joseph, D. N. (Ed.). (2000). Good Manufacturing Practices for Phar-
maceuticals: A Plan for Total Quality Control from Manufacturer to
Consumer. CRC Press.
[26] Zacharia, Z. G., & Mentzer, J. T. (2004). Logistics salience in a chang-
ing environment. Journal of Business Logistics, 25(1), 187-210. DOI:
10.1108/IJLM-10-2012-0113
[27] Phelps, C. E., & Madhavan, G. (2017). Using multicriteria approaches
to assess the value of health care. Value in Health, 20(2), 251-255. DOI:
10.1016/j.jval.2016.11.011
[28] Krekora, M. (2008). Contract manufacturing of medicines. Kluwer Law
International BV.
[29] Aghayan, H. R., Arjmand, B., & Burger, S. R. (2016). GMP facilities for
clinical cell therapy product manufacturing: a brief review of require-
ments and design considerations. Perinatal Tissue-Derived Stem Cells,
215-227. DOI: 10.5812/ans.68497
[30] Reinhardt, I. C., Oliveira, J. C., & Ring, D. T. (2021). Industry 4.0 and
the future of the pharmaceutical industry. Pharm. Eng.
20 Digitalization in the Pharmaceutical Industry: Prioritization Throughout

[31] Jaiganesh, V., & Sudhahar, J. C. (2013). Sketching out the hidden lean
management principles in the pharmaceutical manufacturing. Interna-
tional Journal of Scientific and Research Publications, 3(2), 1-12.
[32] NAYEREH, N., JORDI, B., & VESAL, T. (2012). Good
Manufacturing Practice: A New Approach for the 21st
Century. (3), 37-44.
[33] Karmacharya, J. B. (2014). Good manufacturing practices (GMP)
for medicinal products. Promising Pharmaceuticals, 101-148. DOI:
10.5772/49096
[34] Peng, Z., Wu, D., & Zheng, Q. (2013). A level-value estimation
method and stochastic implementation for global optimization. Journal
of Optimization Theory and Applications, 156(2), 493-523.
[35] Vugigi, S. K., Thoithi, G. N., Ogaji, J. I., & Onuonga, S. O. (2019). Good
manufacturing practices in the Kenyan pharmaceutical industry and
impact of facility upgrading on domestic and international sales. East
and Central African Journal of Pharmaceutical Sciences, 22(3),
77-84.
[36] Awad, A., Trenfield, S. J., Gaisford, S., & Basit, A. W.
(2018). 3D printed medicines: A new branch of digital
healthcare. International journal of pharmaceutics, 548(1), 586-596.
DOI: 10.1016/j.ijpharm.2018.07.024
[37] Capel, A. J., Rimington, R. P., Lewis, M. P., & Christie, S.
D. (2018). 3D printing for chemical, pharmaceutical and biologi-
cal applications. Nature Reviews Chemistry, 2(12), 422-436. DOI:
https://doi.org/10.1038/s41570-018-0058-y
[38] Patidar, A., Vinchurkar, K., & Balekar, N. (2018). Digitalisation in
Pharmacy. International Journal of Research in Pharmacy and Phar-
maceutical Sciences, 3(5), 37-43.
[39] Shah, N. (2004). Pharmaceutical supply chains: key issues and strategies
for optimisation. Computers & chemical engineering, 28(6-7), 929-941.
DOI: 10.1016/j.compchemeng.2003.09.022
[40] Lexchin, J., Bero, L. A., Djulbegovic, B., & Clark, O. (2003).
Pharmaceutical industry sponsorship and research outcome and
quality: systematic review. bmj, 326(7400), 1167-1170. DOI:
10.1136/bmj.326.7400.1167
[41] Alloghani, M., Al-Jumeily, D., Hussain, A., Aljaaf, A. J., Mustafina,
J., & Petrov, E. (2018, September). Healthcare services innovations
based on the state-of-the-art technology trend industry 4.0. In 2018 11th
 References 21

International Conference on Developments in eSystems Engineering

(DeSE) (pp. 64-70). IEEE. DOI: 10.1109/DeSE.2018.00016
[42] Steinwandter, V., Borchert, D., & Herwig, C. (2019). Data science tools
and applications on the way to Pharma 4.0. Drug discovery today, 24(9),
1795-1805. DOI: 10.1016/j.drudis.2019.06.005
[43] Arden, N. S., Fisher, A. C., Tyner, K., Lawrence, X. Y., Lee, S. L.,
& Kopcha, M. (2021). Industry 4.0 for pharmaceutical manufacturing:
Preparing for the smart factories of the future. International Journal of
Pharmaceutics, 602, 120554. DOI: 10.1016/j.ijpharm.2021.120554
[44] Sarkis, M., Bernardi, A., Shah, N., & Papathanasiou, M. M.
(2021). Emerging challenges and opportunities in pharmaceuti-
cal manufacturing and distribution. Processes, 9(3), 457. DOI:
https://doi.org/10.3390/pr9030457
[45] Chowdary, B. V., & George, D. (2012). Improvement of manufac-
turing operations at a pharmaceutical company: a lean manufacturing
approach. Journal of Manufacturing Technology Management. DOI:
https://doi.org/10.5772/59027
[46] Pandya, E. J., & Shah, K. V. (2013). CONTRACT MANUFACTURING
IN PHARMA INDUSTRY. Pharma Science Monitor, 4(3).
[47] Sokolov, M. (2020). Decision making and risk management in bio-
pharmaceutical engineering—opportunities in the age of covid-19 and
digitalization. Industrial & Engineering Chemistry Research, 59(40),
17587-17592. DOI: 10.1021/acs.iecr.0c02994
[48] Rantanen, J., & Khinast, J. (2015). The future of pharmaceutical
manufacturing sciences. Journal of pharmaceutical sciences, 104(11),
3612-3638. DOI: 10.1002/jps.24594
[49] Ganesh, S. (2020). Continuous Pharmaceutical Manufacturing: Systems
Integration for Process Operations Management (Doctoral dissertation,
Purdue University Graduate School).
[50] Mendenhall, D. W., & Kontny, M. J. (2010). CDMO Industry Update.
[51] Hurter, P., Thomas, H., Nadig, D., Emiabata-Smith, D., & Paone,
A. (2013). Implementing continuous manufacturing to streamline and
accelerate drug development. AAPS newsmagazine, 16, 15-19.
[52] Coyle, D., & Nguyen, D. (2020). No plant, no problem? Facto-
ryless manufacturing, economic measurement and national manu-
facturing policies. Review of International Political Economy, 1-21.
DOI: https://doi.org/10.1080/09692290.2020.1778502
[53] May, M. (2021). Adaptability of CDMOs Sorely Tested by COVID-
19: surviving and thriving though COVID-19-imposed rigors, contract
22 Digitalization in the Pharmaceutical Industry: Prioritization Throughout

development and manufacturing organizations are confident of meeting

future challenges. Genetic Engineering & Biotechnology News, 41(6),
60-62. https://www.genengnews.com/insights/adaptability-of-cdmos-
sorely-tested-by-covid-19/
[54] Chircu, A. M., Sultanow, E., & Sözer, L. D. (2017). A reference archi-
tecture for digitalization in the pharmaceutical industry. INFORMATIK
2017. DOI: 10.18420/in2017_205

Biographies of Authors

Sudhanshu Mishra

Sudhanshu Mishra received his M. Pharm (Pharmaceutics) from Rajiv

Gandhi Proudyogiki Vishwavidyalaya and is presently employed as a teach-
ing faculty member at the Madan Mohan Malaviya University of Technology
in Gorakhpur. During his M. Pharm studies, he concentrated on developing
a herbal topical formulation for the treatment of arthritis. At present, he is
working on a variety of literature projects, including authoring review articles
for various innovative approaches and technologies for treating chronic dis-
orders. He has taken part in international seminars, conferences, workshops,
and oral presentations, among other things. This book chapter is one of the
most influential contributions to his interest in technology and future study.
Digitalization in the Pharmaceutical Industry: Prioritization Throughout
the Digital Transformation
Faraj, S. , Renno, W. , & Bhardwaj, A. (2021). Unto the breach: What the COVID-19 pandemic
exposes about digitalization. Information and Organization, 31(1), 100337. DOI:
10.1016/j.infoandorg.2021.100337
Iglehart, J. K. (2014). Connected health: emerging disruptive technologies. health affairs, 33(2),
190–190. DOI: 10.1377/hlthaff.2014.0042
Fecha, P. M. S. (2017). The Return of the Investment of the Digital Channels in Pharmaceutical
Industry (Doctoral dissertation, Universidade de Coimbra).
Schaufelberger, D. E. , Koleck, M. P. , Beutler, J. A. , Vatakis, A. M. , Alvarado, A. B. , Andrews,
P. , ... & Forenza, S. (1991). The large-scale isolation of bryostatin 1 from Bugula neritina
following current good manufacturing practices. Journal of natural products, 54(5), 1265–1270.
DOI: 10.1021/np50077a004
Anthony Jr, B. , & Abbas Petersen, S. (2021). Examining the digitalisation of virtual enterprises
amidst the COVID-19 pandemic: a systematic and meta-analysis. Enterprise Information
Systems, 15(5), 617–650. DOI: https://doi.org/10.1080/17517575.2020.1829075
Ngamvichaikit, A. (2021). Leveraging design thinking for pharmaceutical digital marketing. Asian
J. Business Res, 2021, 11. DOI: 10.14707/ajbr.210102
Sehlstedt, U. , Bohlin, N. , de Maré, F. , & Beetz, R. (2016). Embracing digital health in the
pharmaceutical industry. International Journal of Healthcare Management, 9(3), 145–148. DOI:
https://doi.org/10.1080/20479700.2016.1197513
Lakshmi, B. , & Patel, S. (2020). Digital Marketing in Pharmaceutical Industry–An Overview and
Assessment.
Lakshmi, B. , & Patel, S. (2020). Digital Marketing in Pharmaceutical Industry–An Overview and
Assessment.
Rosenbaum, M. S. , Ramírez, G. C. , Edwards, K. , Kim, J. , Campbell, J. M. , & Bickle, M. C.
(2017). The digitization of health care retailing. Journal of Research in Interactive Marketing.
DOI: 10.1108/JRIM07-2017-0058
van Velthoven, M. H. , Cordon, C. , & Challagalla, G. (2019). Digitization of healthcare
organizations: the digital health landscape and information theory. International journal of
medical informatics, 124, 49–57. DOI: 10.1016/j.ijmedinf.2019.01.007
Cramer, M. M. (2006). Food plant sanitation: design, maintenance, and good manufacturing
practices. CRC Press. DOI: https://doi.org/10.1201/9781420005943
Patel, K. T. , & Chotai, N. P. (2011). Documentation and records: harmonized GMP
requirements. Journal of young pharmacists, 3(2), 138–150. DOI: 10.4103/0975-1483.80303
Patel, K. T. , & Chotai, N. P. (2008). Pharmaceutical GMP: past, present, and future–a review.
Die Pharmazie-An International Journal of Pharmaceutical Sciences, 63(4), 251–255. DOI:
10.1691/ph.2008.7319
World Health Organization . (2007). WHO guidelines on good manufacturing practices (GMP)
for herbal medicines. World Health Organization.
Harris, J. , & Hill, R. (2010, April). Building a trusted image for embedded systems. In
Proceedings of the Sixth Annual Workshop on Cyber Security and Information Intelligence
Research (pp. 1–4).
Rangarajan, A. (2015). The FDA and Worldwide Current Good Manufacturing Practices and
Quality System Requirements: Guidebook for Finished Pharmaceuticals. Quality Progress,
48(4), 60. https://asq.org/quality-press/display-item?item=H1458
Haleem, R. M. , Salem, M. Y. , Fatahallah, F. A. , & Abdelfattah, L. E. (2015). Quality in the
pharmaceutical industry–A literature review. Saudi pharmaceutical journal, 23(5), 463–469.
DOI: 10.1016/j.jsps.2013.11.004
Abhinaya, N. , Thunga, G. , Muddukrishna, B. S. , Pai, R. , Shenoy, U. R. , Khan, S. , & Pai, K.
G. (2019). Research on effective management of manufacturing defects to avoid product
recalls: a challenge to pharmaceutical industry. Research Journal of Pharmacy and Technology,
12(12), 6124–6132. DOI: 10.5958/0974-360X.2019.01064.3
Abou-El-Enein, M. , Römhild, A. , Kaiser, D. , Beier, C. , Bauer, G. , Volk, H. D. , & Reinke, P.
(2013). Good Manufacturing Practices (GMP) manufacturing of advanced therapy medicinal
products: a novel tailored model for optimizing performance and estimating costs. Cytotherapy,
15(3), 362–383. DOI: 10.1016/j.jcyt.2012.09.006
Taylor, P. (2008). Pharmaceutical excipients: where now for GMP. RAJ Pharma, 19(12),
815–818. DOI: 10.1007/s40005–017–0354–4
Kumar, N. , & Jha, A. (2019). Application of principles of supply chain management to the
pharmaceutical good transportation practices. International Journal of Pharmaceutical and
Healthcare Marketing. DOI: 10.1108/IJPHM-09-2017-0048
George, B. V. C. D. (2012). Improvement of manufacturing operations at a pharmaceutical
company. A lean manufacturing approaches. J. Manuf. Technol. Manag, 23(1), 56–75. DOI:
https://doi.org/10.5772/59027
Lee, F. S. , Wang, X. , & Fu, P. P. (2010). Quality assurance and safety protection of traditional
Chinese herbs as dietary supplements. Funct. Foods East, 431. DOI:
10.1080/10590500902885676
Joseph, D. N. . (Ed.). (2000). Good Manufacturing Practices for Pharmaceuticals: A Plan for
Total Quality Control from Manufacturer to Consumer. CRC Press.
Zacharia, Z. G. , & Mentzer, J. T. (2004). Logistics salience in a changing environment. Journal
of Business Logistics, 25(1), 187–210. DOI: 10.1108/IJLM-10-2012-0113
Phelps, C. E. , & Madhavan, G. (2017). Using multicriteria approaches to assess the value of
health care. Value in Health, 20(2), 251–255. DOI: 10.1016/j.jval.2016.11.011
Krekora, M. (2008). Contract manufacturing of medicines. Kluwer Law International BV.
Aghayan, H. R. , Arjmand, B. , & Burger, S. R. (2016). GMP facilities for clinical cell therapy
product manufacturing: a brief review of requirements and design considerations. Perinatal
Tissue-Derived Stem Cells, 215–227. DOI: 10.5812/ans.68497
Reinhardt, I. C. , Oliveira, J. C. , & Ring, D. T. (2021). Industry 4.0 and the future of the
pharmaceutical industry. Pharm. Eng.
Jaiganesh, V. , & Sudhahar, J. C. (2013). Sketching out the hidden lean management principles
in the pharmaceutical manufacturing. International Journal of Scientific and Research
Publications, 3(2), 1–12.
Nayereh, N. , Jordi, B. , & Vesal, T. (2012). Good Manufacturing Practice: A New Approach for
the 21st Century. (3), 37–44.
Karmacharya, J. B. (2014). Good manufacturing practices (GMP) for medicinal products.
Promising Pharmaceuticals, 101–148. DOI: 10.5772/49096
Peng, Z. , Wu, D. , & Zheng, Q. (2013). A level-value estimation method and stochastic
implementation for global optimization. Journal of Optimization Theory and Applications, 156(2),
493–523.
Vugigi, S. K. , Thoithi, G. N. , Ogaji, J. I. , & Onuonga, S. O. (2019). Good manufacturing
practices in the Kenyan pharmaceutical industry and impact of facility upgrading on domestic
and international sales. East and Central African Journal of Pharmaceutical Sciences, 22(3),
77–84.
Awad, A. , Trenfield, S. J. , Gaisford, S. , & Basit, A. W. (2018). 3D printed medicines: A new
branch of digital healthcare. International journal of pharmaceutics, 548(1), 586–596. DOI:
10.1016/j.ijpharm.2018.07.024
Capel, A. J. , Rimington, R. P. , Lewis, M. P. , & Christie, S. D. (2018). 3D printing for chemical,
pharmaceutical and biological applications. Nature Reviews Chemistry, 2(12), 422–436. DOI:
https://doi.org/10.1038/s41570-018-0058-y
Patidar, A. , Vinchurkar, K. , & Balekar, N. (2018). Digitalisation in Pharmacy. International
Journal of Research in Pharmacy and Pharmaceutical Sciences, 3(5), 37–43.
Shah, N. (2004). Pharmaceutical supply chains: key issues and strategies for optimisation.
Computers & chemical engineering, 28(6–7), 929–941. DOI:
10.1016/j.compchemeng.2003.09.022
Lexchin, J. , Bero, L. A. , Djulbegovic, B. , & Clark, O. (2003). Pharmaceutical industry
sponsorship and research outcome and quality: systematic review. bmj, 326(7400), 1167–1170.
DOI: 10.1136/bmj.326.7400.1167
Alloghani, M. , Al-Jumeily, D. , Hussain, A. , Aljaaf, A. J. , Mustafina, J. , & Petrov, E. (2018,
September). Healthcare services innovations based on the state-of-the-art technology trend
industry 4.0. In 2018 11th International Conference on Developments in eSystems Engineering
(DeSE) (pp. 64–70). IEEE. DOI: 10.1109/DeSE.2018.00016
Steinwandter, V. , Borchert, D. , & Herwig, C. (2019). Data science tools and applications on the
way to Pharma 4.0. Drug discovery today, 24(9), 1795–1805. DOI:
10.1016/j.drudis.2019.06.005
Arden, N. S. , Fisher, A. C. , Tyner, K. , Lawrence, X. Y. , Lee, S. L. , & Kopcha, M. (2021).
Industry 4.0 for pharmaceutical manufacturing: Preparing for the smart factories of the future.
International Journal of Pharmaceutics, 602, 120554. DOI: 10.1016/j.ijpharm.2021.120554
Sarkis, M. , Bernardi, A. , Shah, N. , & Papathanasiou, M. M. (2021). Emerging challenges and
opportunities in pharmaceutical manufacturing and distribution. Processes, 9(3), 457. DOI:
https://doi.org/10.3390/pr9030457
Chowdary, B. V. , & George, D. (2012). Improvement of manufacturing operations at a
pharmaceutical company: a lean manufacturing approach. Journal of Manufacturing Technology
Management. DOI: https://doi.org/10.5772/59027
Pandya, E. J. , & Shah, K. V. (2013). Contract Manufacturing In Pharma Industry. Pharma
Science Monitor, 4(3).
Sokolov, M. (2020). Decision making and risk management in biopharmaceutical
engineering—opportunities in the age of covid-19 and digitalization. Industrial & Engineering
Chemistry Research, 59(40), 17587–17592. DOI: 10.1021/acs.iecr.0c02994
Rantanen, J. , & Khinast, J. (2015). The future of pharmaceutical manufacturing sciences.
Journal of pharmaceutical sciences, 104(11), 3612–3638. DOI: 10.1002/jps.24594
Ganesh, S. (2020). Continuous Pharmaceutical Manufacturing: Systems Integration for Process
Operations Management (Doctoral dissertation, Purdue University Graduate School).
Mendenhall, D. W. , & Kontny, M. J. (2010). CDMO Industry Update.
Hurter, P. , Thomas, H. , Nadig, D. , Emiabata-Smith, D. , & Paone, A. (2013). Implementing
continuous manufacturing to streamline and accelerate drug development. AAPS
newsmagazine, 16, 15–19.
Coyle, D. , & Nguyen, D. (2020). No plant, no problem? Factoryless manufacturing, economic
measurement and national manufacturing policies. Review of International Political Economy,
1–21. DOI: https://doi.org/10.1080/09692290.2020.1778502
May, M. (2021). Adaptability of CDMOs Sorely Tested by COVID19: surviving and thriving
though COVID-19-imposed rigors, contract development and manufacturing organizations are
confident of meeting future challenges. Genetic Engineering & Biotechnology News, 41(6),
60–62. https://www.genengnews.com/insights/adaptability-of-cdmossorely-tested-by-covid-19/
Chircu, A. M. , Sultanow, E. , & Sözer, L. D. (2017). A reference architecture for digitalization in
the pharmaceutical industry. INFORMATIK 2017. DOI: 10.18420/in2017_205

Applications of Industry 4.0 in the Pharmaceutical Sector

Paul, S. , Rabbani, M. S. , Kundu, R. K. and Zaman, S. M. R. -2014) “A review of smart
technology (Smart Grid) and its features,” in the Proceedings of the International Conference on
Non-Conventional Energy (ICONCE 2014) Kalyani, India, 200–203.
Adhikari, I. , and Singhal, N. (2020) Industry 4.0 preparedness in Indian pharmaceutical
companies - A review and agenda for future research. MDIM Business Review . 1-1, 39–45.
Eurotransis: The Industrial Revolution . Was it so important?. Available at:
https://eurotransis.com/en/the-industrial-revolution-was-it-soimportant/ [accessed Jan 5, 2022].
Mohajan, H. K. (2019) The First Industrial Revolution: Creation of a New Global Human Era.
Journal of Social Sciences and Humanities . 5-4, 377–387.
Groumpo, P. P. (2021) A Critical Historical and Scientific Overview of all Industrial Revolutions.
IFAC-PapersOnLine, 54-13, 464–471. DOI: https://doi.org/10.1016/j.ifacol.2021.10.492.
Kagermann, H. , Helbig, J. , Hellinger, A. , Wahlster, W. (2013) Recommendations for
Implementing the Strategic Initiative Industry 4.0: Securing the Future of German Manufacturing
Industry. Final Report of the Industry 4.0 Working Group Forschungsunion .
Mohd, J. , Haleem A. (2019) Industry 4.0 applications in medical field: A brief review. Curr. Med.
Res. Pract . 9,102–109. DOI: https://doi.org/10.1016/j.cmrp.2019.04.001.
Sharma, A. , and Singh, B. J. (2020) Evolution of Industrial Revolutions: A Review.
International Journal of Innovative Technology and Exploring Engineering , 9. 66–73.
Recommendations for Implementing the Strategic Initiative Industries 4.0 : Final Report of the
Industries 4.0 Working Group. Available at:
https://www.din.de/blob/76902/e8cac883f42bf28536e7e8165993f1fd /recommendations-for-
implementing-industry-4-0-data.pdf [accessed Jan 5, 2022].
Crnjac, M. , Veža, I. (2017) From concept to the introduction of Industry 4.0. Int. J. Ind. Eng.
Manag. 8-1, 21–30.
Epicor :What is Industry 4.0—the Industrial Internet of Things (IIoT)?. Available at:
https://www.epicor.com/en-in/resources/articles/what-isindustry-4-0/ [accessed Jan 5, 2022].
Qin, J. , Liu, Y. , Grosvenor, R. A. (2016) Categorical Framework of Manufacturing for Industry
4.0 and beyond. Procedia CIRP . 52, 173–178. DOI:
https://doi.org/10.1016/j.procir.2016.08.005.
Mrugalska, B. , Wyrwicka, M. K. (2017) Towards Lean Production in Industry 4.0. Procedia Eng.
182, 466–473. DOI: https://doi.org/10.101 6/j.proeng.2017.03.135.
Market & Market : Industry 4.0 Market. Available at:
https://www.marketsandmarkets.com/Market-Reports/industry-4-market-102536746.html
[accessed Jan 5, 2022].
Adebayo, A. O. , Chaubey, M. S. , Numbu, L. P. (2019) Industry 4.0: The fourth industrial
revolution and how it relates to the application of Internet of Things (IoT). J. multidiscip. eng. sci.
technol. 5-2, 2477–2482.
LabhGroup : 6 Key Benefits of Industry 4.0 for Businesses. Available at:
https://labhgroup.com/insights/6-benefits-of-industry-4-0/ [accessed Jan 5, 2022].
The Main Benefits and Challenges of Industry 4.0 Adoption in Manufacturing . Available at:
https://www.infopulse.com/blog/the-mainbenefits-and-challenges-of-industry-4-0-adoption-in-
manufacturing [accessed Jan 5, 2022].
Industry 4.0 And Smart Factory : How These Can Benefit Businesses. Available at:
https://www.tm-robot.com/en/blog/industry-4-smart-factor-business-benefits/ [accessed Jan, 6
2022].
Prescient Technologies : Benefits of Industry 4.0. Available at: https://www.pre-
scient.com/knowledge-center/industry-4-0/benefits-of-ind ustry-4-0.html [accessed Jan 6, 2022].
Woboton: 5 Key Benefits of Industry 4.0 for Factories. Available at: https://woboton.com/5-key-
benefits-of-industry-40-for-factories/ [accessed Jan 6, 2022].
Industrial Internet of things (IIoT) and Industry 4.0 : Are you ready for it?. Available at:
https://radixweb.com/blog/what-is-industry-4-0 [accessed Jan 5, 2022].
How can Industry 4.0 benefit my business? . Available at: https://www.bdc.ca/en/articles-
tools/technology/invest-technology/how-can-indust ry-benefit-my-business [accessed Jan 5,
2022].
SLCONTROLS : Benefits of Industry 4.0. Available at: https://slcontrols.com/en/benefits-of-
industry-4-0/ [accessed Jan 6, 2022].
Gajdzik, B. , Grabowska, S. , Saniuk, S. (2021) A Theoretical Framework for Industry 4.0 and its
Implementation with Selected Practical Schedules. Energies . 14-4, 940. DOI:
https://doi.org/10.3390/en14040940.
Guru99: What is Big Data? Introduction , Types, Characteristics, Examples. Available at:
https://www.guru99.com/what-is-big-data.html [accessed Jan 6, 2022].
Witkowski, K. (2017) Internet of Things, Big Data, Industry 4.0 - Innovative Solutions in Logistics
and Supply Chains Management. Procedia Eng. 182, 763–769. DOI:
https://doi.org/10.1016/j.proeng.2017.03.1 97.
Builtin:17 Big Data Examples and Applications. Available at: https://builtin.com/big-data/big-
data-examples-applications [accessed Jan 6, 2022].
Zhong, R. Y. , Xu, X. , Klotz, E. , Newman, S. T. N. (2017) Intelligent Manufacturing in the
Context of Industry 4.0: A Review. Engineering . 3-5, 616–630. DOI:
https://doi.org/10.1016/J.ENG.2017.05.015.
Builtin: 27 Top Internet of Things Examples You Should Know. Available at:
https://builtin.com/internet-things/iot-examples [accessed Jan 6, 2022].
Tay, S. I. , Lee, T. C. , Hamid, N. A. A. , Ahmad, A. N. A. (2018) An Overview of Industry 4.0:
Definition, Components, and Government Initiatives. J. Adv. Res. Dyn. Control Syst. 10-14,
1379–1387.
SAP: What is Industry 4.0?. Available at: https://insights.sap.com/whatis-industry-4-0/ [accessed
Jan 6, 2022].
Machinemterics: Emerging Industry 4.0 Technologies with Real-World Examples. Available at:
https://www.machinemetrics.com/blog/industry-4-0-technologies [accessed Jan 6, 2022].
Vaidya, S. , Ambad, P. , and Bhosle, S. (2018) Industry 4.0 - A Glimpse. Procedia Manuf . 20,
233–238. DOI: https://doi.org/10.1016/j.promfg.2018.02.034.
Netcov: What is Cloud Computing?. Available at: https://www.netcov.com/what-is-cloud-
computing/_ [accessed Jan 6, 2022].
StudiousGuy: 11 Examples of Augmented Reality in Everyday Life. Available at:
https://studiousguy.com/examples-augmented-reality/ [accessed Jan 6, 2022].
Dilberoglu, U. M. , Gharehpapagh, B. , Yaman, U. , Dolen, M. (2017) The Role of Additive
Manufacturing in the Era of Industry 4.0. Procedia Manuf . 11, 545–554. DOI:
https://doi.org/10.1016/j.promfg.2017.07.1 48.
NeoMetrix Technologies : 7 Examples of 3D Printing in the World Today. Available at:
https://3dscanningservices.net/blog/7-examples-of3d-printing-in-the-world-today/ [accessed Jan
7, 2022].
Woodcock, J. (2004) The Concept of Pharmaceutical Quality. Am. Pharm. Rev. 7-6, 10–15.
Stegemann, S. (2016) The future of pharmaceutical manufacturing in the context of the
scientific, social, technological and economic evolution. Eur. J. Pharm. Sci. 90, 8–13. DOI:
10.1016/j.ejps.2015.11.003.
Weichhart, G. , Molina, A. , Chen, D. , Whitman, L. , and Vernadat, F. (2015) Challenges and
Current Developments for sensing, Smart and Sustainable Enterprise Systems, Computers in
Industry. Comput Ind. 79, 34–46, DOI: 10.1016/j.compind.2015.07.002.
Reinhardt, I. C. , Oliveira, J. C. , and Ring, D. T. (2021) Industry 4. 0 and the Future of the
Pharmaceutical Industry. Pharm. Eng. 41-2.
Herwig, C. , Woelbeling, C. , Zimmer, C. (2017) A Holistic Approach to Production Control.
Pharm. Eng.
Markarian, J. (2018) Pharma 4.0. Pharm. Technol. 42-4. 1–24.
Interfacing: What is Pharma 4.0?. Available at: https://www.interfacing.com/pharma-4-0
[accessed Jan 6, 2022].
Vimachem IIOT Pharma 4. 0 AI Platform : A practical guide to pharma 4. 0 realization, Available
at: https://www.vimachem.com/resources/p harma-4-0/ [accessed Jan 7, 2022].
From Industrie4. 0 to Pharma 4. 0 Operating model and The Holistic ICH Control Strategy.
Available at https://gosgmp.ru/download/Materia ly/ivgmp/2019-09-23/04-en/Volbeling_angl.pdf
[accessed Jan 6, 2022].
Manzano, T. , and Langer, G. (2018) Getting Ready for Pharma 4.0TM. Pharm. Eng . 72–79.
ISPE Connecting Pharmaceutical Knowledge , Pharma 4.0TM: Hype or Reality?. Available at:
https://ispe.org/pharmaceutical-engineering/julyaugust-2018/pharma-40tm-hype-or-reality
[accessed Jan 7, 2022].
Inada, Y. (2019) Continuous Manufacturing Development in Pharmaceutical and Fine
Chemicals Industries. Mitsui & Co. Global Strategic Studies Institute Monthly Report.
U.S. Food and Drug Administration , Modernizing the Way Drugs Are Made: A Transition to
Continuous Manufacturing. Available at: https://www.fda.gov/drugs/news-events-human-
drugs/modernizing-way-dr ugs-are-made-transition-continuous-manufacturing [accessed Jan 7,
2022].
Tefen Management Consulting : The Impact of Industry 4. 0 on the Pharma Industry. Available
at: https://www.tefen.com/insights/industr
ies/Patient_Care/the_impact_of_industry_40_on_the_pharma_industry [accessed Jan 6, 2022].
Domokos, A. , Nagy, B. , Szilágyi, B. , Marosi, G. and Nagy, Z. K. (2021) Integrated Continuous
Pharmaceutical Technologies—A Review. Org. Process Res. Dev . 25-4, 721–739. DOI:
https://doi.org/10.1021/acs.op rd.0c00504.
Hock, S. C. , Siang, T. K. and Wah, C. L. (2021) Continuous manufacturing versus batch
manufacturing: benefits, opportunities and challenges for manufacturers and regulators. GaBI
Journal.10-1, 44–56. DOI: 10.5639/gabij.2021.1001.004
John Klaess , 8 Trends in Pharmaceutical Manufacturing to Watch in 2022, Available at:
https://tulip.co/blog/pharmaceutical-manufacturingtrends-to-watch/ [accessed Jan 8, 2022].
Veeva: How Digital Quality Management is Transforming Pharma Manufacturing, Available at:
https://www.veeva.com/wp-content/uploads/2 020/05/Transforming-Pharma-Manufacturing
[accessed Jan 6, 2022].
Branke, J. , Farid, S. S. , and Shah, N. (2016) Industry 4.0: A vision for personalized medicine
supply chains?. Cell gene ther. Insights . 263–270.DOI: 10.18609/cgti.2016.027.
Narayanan, H. et al. (2020) Bioprocessing in the Digital Age: The Role of Process Models.
Biotechnol J . 15-1, e1900172. DOI: 10.1002/biot.201900172.
Hariry, R. E. , Barenji, R. V. , and Paradkar A. (2022) From Industry 4. 0 to Pharma 4.0:
Handbook of Smart Materials, Technologies, and Devices. Drug Discov. Today . 27-1, 315-
325.DOI: 10.1007/978-3-03058675-1_4-1.
Digitization, automation, and online testing : The future of pharma quality control. McKinsey &
Company . Available at: https://www.mckinsey.com/industries/life-sciences/our-
insights/digitization-automation-and-online-testing-the-future-of-pharma-quality-control
[accessed Jan 8, 2022].
Grumbach, E. Emerging Technologies Required for Pharma 4.0. Available at:
https://www.technologynetworks.com/drug-discovery/articles/emerging-technologies-required-
for-pharma-40-346220 [accessed Jan 6, 2022].
Hole, G. , Hole, A. S. , and McFalone-Shaw, I. (2021). Digitalization in pharmaceutical industry:
What to focus on under the digital implementation process?. Int J Pharm X . 3-100095. DOI:
https://doi.org/10.1016/j.ijpx.2021.100095
Krishnamurthy, S. Pharma 4.0: Redefining Product Development and Regulatory Operations.
Pharmexec.com . Available at: https://www.pharmexec.com/view/pharma-4-0-redefining-
product-development-and-regulatory-operations [accessed Jan 7, 2022].
Alagarsamy, S. , Kandasamy, R. , Subbiah, L. , and Selvamani, P. (2019) Applications of
Internet of Things in Pharmaceutical Industry. SSRN Electronic Journal . 1–14. DOI:
10.2139/ssrn.3441059.
Gralla, P. Speeding drug discovery with AI and big data. Available at:
https://www.hpe.com/us/en/insights/articles/speeding-drug-discoverywith-ai-and-big-data-
1802.html [accessed Jan 7, 2022].
Tripathi, M. K. , et al. (2021) Evolving scenario of big data and Artificial Intelligence (AI) in drug
discovery. Mol Divers. 25, 1439–1460. DOI: https://doi.org/10.1007/s11030-021-10256-w.
Abel, J. Digital Transformation of Pharma and Biotech. Arc Report Abstract. Available at:
https://www.arcweb.com/blog/digitaltransformation?pharma-biotech [accessed 7, 2022].
Pharma IQ: Automation , IoT and the future of smarter research environments. Available at:
https://www.pharma-iq.com/preclinical-discoveryand-development/news/automation-iot-and-the-
future-of-smarterresea rch-environment [accessed Jan 7, 2022].
Jingshan, L. , Carayon, P. (2021) Health Care 4.0: A vision for smart and connected health
care, IISE Trans Healthc Syst Eng . 11-3, 171–180. DOI: 10.1080/24725579.2021.1884627.
Paul, S. et al. (2021) Industry 4.0 Applications for Medical/Healthcare Services. J. Sens.
Actuator Netw . 10-3, 43. DOI: https://doi.org/10.3390/jsan10030043.
Jayaraman, P. P. et al. (2019) Healthcare 4.0: A review of frontiers in digital health. WIREs Data
Min Knowl Discov . 10-2, e1350. DOI: https://doi.org/10.1002/widm.1350.
Wetterneck, T. B. et al. (2011). Factors contributing to an increase in duplicate medication order
errors after CPOE implementation. J Am Med Inform Assoc . 18-6, 774-82. DOI:
10.1136/amiajnl-2011-000255.
Nematollahi, M. et al. (2016) Economic and social collaborative decision-making on visit interval
and service level in a two-echelon pharmaceutical supply chain. J. Clean. Prod. 142-4,
3956–3969. DOI:10.1016/j.jclepro.2016.10.062.
Trappey, A. J. C. , Trappey, C. V. , Fan, C. Y. , Hsu, A. P. T. , Li, X. K. , Lee, I. J. Y. (2017). IoT
patent roadmap for smart logistic service provision in the context of Industry 4.0. J. Chin. Inst.
Eng . 40-7, 1–10. DOI:10.1080/02533839.2017.1362325.
Hofmann, E. , Rüsch, M. (2017) Industry 4. 0 and the current status as well as future prospects
on logistics. Comput Ind . 89, 23–34. DOI: https://doi.org/10.1016/j.compind.2017.04.002.
Ding, B. (2018) Pharma Industry 4.0: Literature review and research opportunities in sustainable
pharmaceutical supply chains. Process Saf Environ Prot. 119,115–130. DOI:
https://doi.org/10.1016/j.psep.2018. 06.031.
Mohamed B. D. , Hassini, E. and Bahroun, Z. (2019) Internet of things and supply chain
management: A literature review. Int. J. Prod. Res . 57:15–16, 4719-4742. DOI:
10.1080/00207543.2017.1402140.
Toronto Institute of Pharmaceutical Technology : 3 Ways Pharma 4. 0 Could Change
Pharmaceutical Quality Assurance and Quality Control. Available at:
https://www.tipt.com/blog/3-ways-pharma-4-0could-change-pharmaceutical-quality-assurance-
and-quality-control/ [accessed Jan 8, 2022].
Srikrishna S. 5. 0 Ways Quality 4. 0 Will Improve Manufacturing. Available at:
https://www.pda.org/pda-letter-portal/home/fullarticle/5.0-ways-quality-4.0-will-improve-
manufacturing [accessed Jan 8, 2022].
Pharmaceutical online : Achieving Integrated Quality Through A Continued Process Verification
Program. Available at: https://www.pharmaceuticalonline.com/doc/achieving-integrated-quality-
through-a-continued-process-verification-program-0001 [accessed Jan 8, 2022].
Innopharma technology : What Is Quality 4.0?. Available at:
https://www.innopharmatechnology.com/news/revolutionise-quality-through-quality-4 [accessed
Jan 8, 2022].
Five things to consider for building an Industry 4.0-compatible supply chain . Available at:
https://www.pharmaceutical-technology.com/spon sored/building-industry-40-compatible-
supply-chain/ [accessed Jan 8, 2022].
Arden, N. S. et al. (2021) Industry 4. 0 for pharmaceutical manufacturing: Preparing for the
smart factories of the future, Int. J. Pharm . 602, 120554. DOI:
https://doi.org/10.1016/j.ijpharm.2021.120554.
Gardner, E. The next industrial revolution: Packaging and ‘Industry 4.0’, Packaging Gateway.
Available at: https://www.packaginggateway.com/features/next-industrial-revolution packaging-
industry-40/, [accessed Jan 8, 2022].
Hammer, C. (2018) Digitisation & Industry 4. 0 in Pharma Production. ONdrugDelivery
Magazine . 83, 81–83.
Startups Insights : 5 Top Emerging Pharma 4. 0 Impacting The Industry, Available at:
https://www.startus-insights.com/innovators-guide/5-topemerging-pharma-4-0-startups-
impacting-the-industry/ [accessed Jan 8, 2022].
QbDVision , Available at: https://www.qbdvision.com/# [accessed Jan 9, 2022].
Electrosan Technologies. Available at: https://electrosan.co.in/ [accessed Jan 9, 2022].
Gosilico, Available at: https://www.linkedin.com/company/gosilico/ [accessed Jan 9, 2022].
Smart factory , Available at: https://www.smartfactory.it/flexim-en.html [accessed Jan 9, 2022].

Blockchain in the Pharmaceutical Industry: Opportunities and

Challenges
Siyal, A. A. , Junejo, A. Z. , Zawish, M. , Ahmed, K. , Khalil, A. , & Soursou, G. (2019).
Applications of blockchain technology in medicine and healthcare: Challenges and future
perspectives. Cryptography, 3(1), 3.
Griebel, L. , Prokosch, H. U. , Köpcke, F. , Toddenroth, D. , Christoph, J. , Leb, I. , ... &
Sedlmayr, M. (2015). A scoping review of cloud computing in healthcare. BMC medical
informatics and decision making, 15(1), 1–16.
Bhatti, A. , Siyal, A. A. , Mehdi, A. , Shah, H. , Kumar, H. , & Bohyo, M. A. (2018, February).
Development of cost-effective tele-monitoring system for remote area patients. In 2018
International Conference on Engineering and Emerging Technologies (ICEET) (pp. 1–7). IEEE.
Zhang, P. , White, J. , Schmidt, D. C. , Lenz, G. , & Rosenbloom, S. T. (2018). FHIRChain:
applying blockchain to securely and scalably share clinical data. Computational and structural
biotechnology journal, 16, 267–278.
Zhang, J. , Xue, N. , & Huang, X. (2016). A secure system for pervasive social network-based
healthcare. Ieee Access, 4, 9239–9250.
Kuo, T. T. , Kim, H. E. , & Ohno-Machado, L. (2017). Blockchain distributed ledger technologies
for biomedical and health care applications. Journal of the American Medical Informatics
Association, 24(6), 1211–1220.
Griggs, K. N. , Ossipova, O. , Kohlios, C. P. , Baccarini, A. N. , Howson, E. A. , & Hayajneh, T.
(2018). Healthcare blockchain system using smart contracts for secure automated remote
patient monitoring. Journal of medical systems, 42(7), 1–7.
Chen, Y. , Ding, S. , Xu, Z. , Zheng, H. , & Yang, S. (2019). Blockchainbased medical records
secure storage and medical service framework. Journal of medical systems, 43(1), 1–9.
Wang, S. , Wang, J. , Wang, X. , Qiu, T. , Yuan, Y. , Ouyang, L. , ... & Wang, F. Y. (2018).
Blockchain-powered parallel healthcare systems based on the ACP approach. IEEE
Transactions on Computational Social Systems, 5(4), 942–950.
Nakamoto, S. (2008). Bitcoin: A peer-to-peer electronic cash system. Decentralized Business
Review, 21260.
A. Jeffries . Blockchain is meaningless.
https://www.theverge.com/2018/3/7/17091766/blockchain-bitcoin-ethereum-cryptocurrency-
meaning, Mar. 2018.
Walch, A. (2017). The Path of the Blockchain Lexicon (and the Law) 36 Review of Banking &
Financial Law 713. University College London, 239.
Bogoeva, A. (2018). Blockchain Technology in Healthcare: Opportunities and Challenges
(Doctoral dissertation, Master Thesis, University of Mannheim).
ISO/TC 307 - Blockchain and distributed ledger technologies.
https://www.iso.org/committee/6266604/x/catalogue/.
Seebacher, S. , & Schüritz, R. (2017, May). Blockchain technology as an enabler of service
systems: A structured literature review. In International conference on exploring services
science (pp. 12–23). Springer, Cham.
Sultan, K. , Ruhi, U. , & Lakhani, R. (2018). Conceptualizing blockchains: Characteristics &
applications. arXiv preprint arXiv:1806.03693.
Kruijff, J. D. , & Weigand, H. (2017, June). Understanding the blockchain using enterprise
ontology. In International Conference on Advanced Information Systems Engineering (pp.
29–43). Springer, Cham.
Z. V. Naumann . The Evolution of the Cryptographic Hash Function in Blockchains.
https://medium.com/shokone/hash-no-not-that-kind-the-crypto-kind-2e8bf616aa24, Oct. 2017.
IBM Knowledge Center - Symmetric cryptography.
https://www.ibm.com/support/knowledgecenter/en/SSB23S_1.1.0.14/gtps7/s7symm.html.
IBM Knowledge Center - Public key cryptography.
https://www.ibm.com/support/knowledgecenter/en/SSB23S_1.1.0.14/gtps7/s7pkey.html.
DiffieHellman key exchange.
https://en.wikipedia.org/w/index.php?title=Diffie%E2%80%93Hellman_key_exchange&oldid=85
8357713, Sept. 2018. Page Version ID: 858357713.
Sun, J. , Yan, J. , & Zhang, K. Z. (2016). Blockchain-based sharing services: What blockchain
technology can contribute to smart cities. Financial Innovation, 2(1), 1–9.
Kruijff, J. D. , & Weigand, H. (2017, June). Understanding the blockchain using enterprise
ontology. In International Conference on Advanced Information Systems Engineering (pp.
29–43). Springer, Cham.
Mougayar, W. (2016). The business blockchain: promise, practice, and application of the next
Internet technology. John Wiley & Sons.
Gervais, A. , Karame, G. O. , Wüst, K. , Glykantzis, V. , Ritzdorf, H. , & Capkun, S. (2016,
October). On the security and performance of proof of work blockchains. In Proceedings of the
2016 ACM SIGSAC conference on computer and communications security (pp. 3–16).
Narayanan, A. , Bonneau, J. , Felten, E. , Miller, A. , & Goldfeder, S. (2016). Bitcoin and
cryptocurrency technologies: a comprehensive introduction. Princeton University Press.
Bade, P. V. (2019). Pro-active market opportunity identification as a key element in the
development of innovation strategy (Doctoral dissertation, Wien).
Kuo, T. T. , Kim, H. E. , & Ohno-Machado, L. (2017). Blockchain distributed ledger technologies
for biomedical and health care applications. Journal of the American Medical Informatics
Association, 24(6), 1211–1220.
Xia, Q. I. , Sifah, E. B. , Asamoah, K. O. , Gao, J. , Du, X. , & Guizani, M. (2017). MeDShare:
Trust-less medical data sharing among cloud service providers via blockchain. IEEE access, 5,
14757–14767.
Heston, T. (2017). A case study in blockchain healthcare innovation.
How Blockchain Will Revolutionise Clinical Trials, June 2018. Available
online:https://pharmaphorum.com/views-and-analysis/howblockchain-will-revolutionise-clinical-
trials-clinical-trials/ (accessed on 20 November 2018).
Moe Alsumidaie , Blockchain Concepts Emerge in Clinical Trials, Applied Clinical Trials, May
2018. Available online:http://www.appliedclinicaltrialsonline.com/blockchain-concepts-emerge-
clinical-trials (accessed on 15 October 2018).
Benchoufi, M. , Porcher, R. , & Ravaud, P. (2017). Blockchain protocols in clinical trials:
Transparency and traceability of consent. F1000Research, 6.
Clauson, K. A. , Breeden, E. A. , Davidson, C. , & Mackey, T. K. (2018). Leveraging Blockchain
Technology to Enhance Supply Chain Management in Healthcare:: An exploration of challenges
and opportunities in the health supply chain. Blockchain in healthcare today.
Mauri, R. Blockchain for Fraud Prevention: Industry Use Cases. July 2017. Available online:
https://www.ibm.com/blogs/blockchain/2017/07/blockchain-for-fraud-prevention-industry-use-
cases/ (accessed on 16 October 2018).
Swan, M. (2015). Blockchain thinking: The brain as a decentralized autonomous corporation
[commentary]. IEEE Technology and Society Magazine, 34(4), 41–52.
Taylor, P. Applying Blockchain Technology to Medicine Traceability; April 2016. Available
online: https://www.securingindustry.com/pharm aceuticals/applying-blockchain-technology-to-
medicinetraceability/s40/a2766/ (accessed on 16 October 2018).
Plotnikov, V. , & Kuznetsova, V. (2018). The prospects for the use of digital technology
“blockchain” in the pharmaceutical market. In MATEC web of conferences (Vol. 193, p. 02029).
EDP Sciences.
Sylim, P. , Liu, F. , Marcelo, A. , & Fontelo, P. (2018). Blockchain technology for detecting
falsified and substandard drugs in distribution: pharmaceutical supply chain intervention. JMIR
research protocols, 7(9), e10163.
Guzman Trujllo, C. G. (2018). The role of blockchain in the pharmaceutical industry supply
chain as a tool for reducing the flow of counterfeit drugs (Doctoral dissertation, Dublin Business
School).
Fernández-Caramés, T. M. , & Fraga-Lamas, P. (2018). A Review on the Use of Blockchain for
the Internet of Things. Ieee Access, 6, 3297933001.
Investopedia “Blockchains”. Available online: https://www.investopedia.com/terms/1/51-
attack.asp (accessed on 20 October 2018).
Hertig, A. Blockchain’s Once-Feared 51 Percent Attack Is Now Becoming Regular. June 2018.
Available online: https://www.coindesk.com/blockchains-feared-51-attack-nowbecoming-regular/
(accessed on 20 October 2018).
Esposito, C. , De Santis, A. , Tortora, G. , Chang, H. , & Choo, K. K. R. (2018). Blockchain: A
panacea for healthcare cloud-based data security and privacy?. IEEE Cloud Computing, 5(1),
31–37.
McKinlay, J. Blockchain: Background Challenges and Legal Issues; DLA Piper Publications:
London, UK, 2016.
Kamel Boulos, M. N. , Wilson, J. T. , & Clauson, K. A. (2018). Geospatial blockchain: promises,
challenges, and scenarios in health and healthcare. International Journal of Health
Geographics, 17(1), 1–10.
Mackey, T. K. , Kuo, T. T. , Gummadi, B. , Clauson, K. A. , Church, G. , Grishin, D. , ... &
Palombini, M. (2019). ‘Fit-for-purpose?’–challenges and opportunities for applications of
blockchain technology in the future of healthcare. BMC medicine, 17(1), 1–17.

Patient Monitoring using Blockchain

Nakamoto, S. : ‘Bitcoin: A peer-to-peer electronic cash system, 2008.
Johnston, D. ; Yilmaz, S. O. ; Kandah, J. ; Bentenitis, N. ; Hashemi, F. ; Gross, R. ; Wilkinson,
S. ; Mason, S. ; ‘The general theory of decentralized applications, dapps’, GitHub, 2014, 9.
Enderle, J. ; Blanchard, S. ; Bronzino, J. ; Introduction to Biomedical Engineering. Elesevier
2005, 505–548.
Shahriyar, R. ; Bari, M. F. ; Kundu, G. ; Ahamed, S. I. ; Akbar, M. M. ; Intelligent Mobile Health
Monitoring System (IMHMS). Journal of Control and Automation, 2009, 2, 3.
Franklin, S. W. ; Rajan, S. E. ; Personal Area Network for Biomedical Monitoring Systems Using
Human Body as a Transmission Medium, Journal of Bio-Science and BioTechnology. 2010, 2.
Athavan, K. ; Balasubramanian, G. ; Jagadeeshwaran, S. ; and Dinesh, N. ; Automatic
ambulance rescue system. Int J Adv Technol Eng Res. 2012, 86–92.
Bourouis, A. ; Feham, M. ; Ubiquitous mobile health monitoring. 2011, 3(3), 74–82.
Chacko, A. ; Hayajneh, T. ; Security and privacy issues with IoT in healthcare. EAI Endorsed
Transactions on Pervasive Health and Technology, 2018, 4(14).
Zheng, Z. ; Shaoan, X. ; Hongning, D. ; Xiangping, C. ; Huaimin, W. ; An overview of blockchain
technology: Architecture, consensus, and future trends. In 2017 IEEE International Congress on
Big Data (BigData Congress). 2017, 557–564.
Kuo, T. Ting ; Hyeon, E. K. ; Lucila, O. M. ; Blockchain distributed ledger technologies for
biomedical and health care applications. Journal of the American Medical Informatics
Association. 2017, 6, 1211–1220.
Daniel, J. ; Arman, S. ; Mohammed, A. ; Saman, S. ; Ben, A. ; Blockchain Technology,
Cognitive Computing, and Healthcare Innovations. Journal of Advances in Information
Technology. 2017 8, 34–39.
Mettler, Matthias , Blockchain technology in healthcare: The revolution starts here. In 2016
IEEE 18th International Conference on e-Health Networking, Applications and Services
(Healthcom), 2016, 1–3.
Chelladurai, U. ; Pandian, S. ; A novel blockchain based electronic health record automation
system for healthcare, J. Ambient Intell. Humanized Comput. 2021, 1–6.
Zhang, P. ; Schmidt, D. C. ; White, J. ; Lenz, G. ; Blockchain technology use cases in
healthcare, in: Advances in Computers, Elsevier, 2018, 111, 1–41.
Sadiku, M. ; Eze, K. ; Musa, S. “Blockchain technology in healthcare.International Journal of
Advances in Scientific Research and Engineering. 2018, 4, 154–159.
Tandon, A. ; Dhir, A. N. ; Islam, Mantym , A.; Blockchain in healthcare: A systematic literature
review, synthesizing framework and future research agenda. Computers in Industry. 2020, 122,
103–290.
P. J. P. A. T. C. Gaynor, M. ; Tuttle, N. J. ; Adoption of blockchain in health care. Journal of
medical Internet research, 2020, 150–155.
Agbo, C. C. ; Mahmoud, Q. H. ; Eklund, J. M. Blockchain Technology in Healthcare: A
Systematic Review. Healthcare. 2019, 7, 56.
Senthamilarasi, C. ; Jansi Rani, J. ; Vidhya, B. ; and Aritha, H. ; 2018. A smart patient health
monitoring system using IoT. International Journal of Pure and Applied Mathematics. 2018, 119,
59–70.
Alexandru, A. ; Nicolae, B. ; Elena, Ş. ; Paul, C. H. ; and Andrei, Z. ; An IoT based system for
remote patient monitoring. In Procedings of the 17th International Carpathian Control
Conference (ICCC). 2016, 1–6.
Muhammad, T. ; Muhammad, S. ; Shakoor, M. ; and Muhammad, S. ; A lightweight
authentication and authorization framework for blockchainenabled IoT network in health-
informatics. Sustainability.2020, 12, 1721.
Pros and Cons of Telemedicine | eVisit Telehealth Solutions. (n.d.). Retrieved March 01, 2018,
from https://evisit.com/10-pros-and-cons-oftelemedicine/
Sood, S. ; Mbarika, V. ; Jugoo, S. ; Dookhy, R. ; Doarn, C. R. ; Prakash, N. ; and Merrell, R. C. ;
What is telemedicine? A collection of 104 peerreviewed perspectives and theoretical
underpinnings. Telemedicine and e-Health, 2007, 13, (5), 573–590.
What is telemedicine? - Definition from WhatIs.com. (n.d.). Retrieved March 01, 2018, from
http://searchhealthit.techtarget.com/definition/te lemedicine
IOS - Health. (n.d.). Retrieved March 01, 2018, from https://www.apple.com/ios/health/
Zhang, P. ; White, J. ; Schmidt, D. C. ; Lenz, G. ; and Rosenbloom, S. T. ; ‘FHIRChain: Applying
Blockchain to Securely and Scalably Share Clinical Data, Elsevier. 2019, 168–175.
Hong, N. D. ; Zibin; and Yan, Z. ; Blockchain for Internet of Things: A Survey. Internet of Things
Journal. 2019, 6, 8076–8094.
Ana, R. ; Cristian, M. ; Jaime, C. ; Enrique, S. ; and Manuel, D. ; On blockchain and its
integration with IoT. Challenges and opportunities. Future Generation Computer Systems. 2018,
88, 173–190.
Hoe, T. Y. ; Ming F. N. ; Soh, P. ; Seng, K. C. ; Ali, C. ; and Jamal, A. ; IoT Based Real-Time
Remote Patient Monitoring System. 16th IEEE International Colloquium on Signal Processing
Its Applications (CSPA). 2020, 176–179.
Potential of AI in the Advancement of the Pharmaceutical Industry
Arvapalli, S. , and Sharma, J. (2019). Artificial intelligence in pharma industry: A review. Int. J.
Innov. Pharm. Sci. Res. 7(10), 37–50.
Sethuraman, N. (2020). Artificial Intelligence: A new paradigm for pharmaceutical applications in
formulations development. Indian J. Pharm. Educ. Res. 54(4), 843–846.
Shanbhogue, M. H. , Thirumaleshwar, S. , Tm, P. K. , and Kumar, S. H. (2021). Artificial
intelligence in pharmaceutical field-A critical review. Curr. Drug Deliv. 18(10), 1421–1431.
Vyas, M. , Thakur, S. , Riyaz, B. , Bansal, K. K. , Tomar, B. , and Mishra, V. (2018). Artificial
intelligence: the beginning of a new era in pharmacy profession. Asian J. Pharm. 12(2), 72–76.
Hunter, J. (2016). Adopting AI is essential for a sustainable pharma industry. Drug Discov.
World Winter 2017, 69–71.
C. I. F. N. I. F. B. Digital healthcare s.l.gpbullhound. 2013:91643080.
Eren, A. , Subasi, A. , and Coskun, O. (2008). A decision support system for telemedicine
through the mobile telecommunications platform. J. Med. Syst. 32(1), 31–35.
Manne, R. (2021). Machine learning techniques in drug discovery and development. Int. J. Appl.
Res. 7(4), 21–28.
Salman, M. , Ahmed, A. W. , Khan, A. , Raza, B. , and Latif, K. (2017). Artificial intelligence in
biomedical domain an overview of AI based innovations in medical. Int. J. Adv. Comput. Sci.
Appl. 8, 319–327.
Erguzel, T. T. , and Ozekes, S. (2014). Artificial intelligence approaches in psychiatric disorders.
Journal of Neurobehavioral Studies 1, 52–53.
Paul, D. , Sanap, G. , Shenoy, S. , Kalyane, D. , Kalia, K. , and Tekade, R. K. (2021). Artificial
intelligence in drug discovery and development. Drug Discov. Today 26(1), 80–93.
Mak, K. K. , and Pichika, M. R. (2019). Artificial intelligence in drug development: present status
and future prospects. Drug Discov. Today 24(3), 773–780.
Borisa, P. , Singh, D. , and Rathore, K. S. (2020). Impact of artificial intelligence on pharma
industry. Manipal Journal of Pharmaceutical Sciences 6(1), 54–59.
Patel, V. , and Shah, M. (2021). A comprehensive study on artificial intelligence and machine
learning in drug discovery and drug development. Intelligent Medicine.
Cui, R. , and Zhu, F. (2020). Ultrasound modified polysaccharides: A review of structure,
physicochemical properties, biological activities and food applications. Trends Food Sci.
Technol. 107, 491–508.
Soto, A. J. , Ponzoni, I. , and Vazquez, G. E. (2007). Predicting physicochemical properties for
drug design using clustering and neural network learning. In: Brazilian Symposium on
Bioinformatics, 46–57.
Toccaceli, P. , Nouretdinov, I. , and Gammerman, A. (2017). Conformal prediction of biological
activity of chemical compounds. Ann. Math. Artif. Intell. 81(1), 105–123.
Correia, J. , Resende, T. , Baptista, D. , and Rocha, M. (2019). Artificial intelligence in biological
activity prediction. In International Conference on Practical Applications of Computational
Biology & Bioinformatics, Springer, Cham, 164–172.
Kim, H. , Kim, E. , Lee, I. , Bae, B. , Park, M. , and Nam, H. (2020). artificial intelligence in drug
discovery: A comprehensive review of data-driven and machine learning approaches.
Biotechnol. Bioprocess Eng. 25(6), 895–930.
Podlewska, S. , and Kafel, R. (2018). Metstabon—online platform for metabolic stability
predictions. Int. J. Mol. Sci. 19(4), 1–16.
Basile, A. O. , Yahi, A. , and Tatonetti, N. P. (2019). Artificial intelligence for drug toxicity and
safety. Trends Pharmacol. Sci. 40(9), 624–635.
Feng, J. , Lurati, L. , Ouyang, H. , Robinson, T. , Wang, Y. , Yuan, S. , and Young, S. S. (2003).
Predictive toxicology: benchmarking molecular descriptors and statistical methods. J. Chem. Inf.
Comput. Sci. 43(5), 1463–1470.
Zhang, L. , Zhang, H. , Ai, H. , Hu, H. , Li, S. , Zhao, J. , and Liu, H. (2018). Applications of
machine learning methods in drug toxicity prediction. Curr. Top. Med. Chem. 18(12), 987–997.
Xu, Y. , Pei, J. , and Lai, L. (2017). Deep learning based regression and multiclass models for
acute oral toxicity prediction with automatic chemical feature extraction. J. Chem. Inf. Model
57(11), 2672–2685.
Latek, D. , Ekonomiuk, D. , and Kolinski, A. (2007). Protein structure prediction: combining de
novo modeling with sparse experimental data. J. Comput. Chem. 28(10), 1668–1676.
Manoochehri, H. E. , Pillai, A. , and Nourani, M. (2019, November). Graph convolutional
networks for predicting drug-protein interactions. In 2019 IEEE International Conference on
Bioinformatics and Biomedicine (BIBM) (pp. 1223–1225). IEEE.
Chan, H. S. , Shan, H. , Dahoun, T. , Vogel, H. , and Yuan, S. (2019). Advancing drug discovery
via artificial intelligence. Trends Pharmacol. Sci. 40(8), 592–604.
Blaschke, T. , Arús-Pous, J. , Chen, H. , Margreitter, C. , Tyrchan, C. , Engkvist, O. ,
Papadopoulos, K. , and Patronov, A. (2020). REINVENT 2.0: an AI tool for de novo drug design.
J. Chem. Inf. Model. 60(12), 5918–5922.
Arús-Pous, J. , Johansson, S. V. , Prykhodko, O. , Bjerrum, E. J. , Tyrchan, C. , Reymond, J. L.
, Chen, H. , and Engkvist, O. (2019). Randomized SMILES strings improve the quality of
molecular generative models. J. Cheminform. 11(1), 1–13.
Mirbabaie, M. , Stieglitz, S. , and Frick, N. R. (2021). Artificial intelligence in disease
diagnostics: A critical review and classification on the current state of research guiding future
direction. Health Technol. 11(4), 693–731.
Mitchell, T. , Cohen, W. , Hruschka, E. , Talukdar, P. , Yang, B. , Betteridge, J. , Carlson, A. ,
Dalvi, B. , Gardner, M. , Kisiel, B. , and Krishnamurthy, J. (2018). Never-ending learning.
Commun. ACM 61(5), 103–115.
Yan, Y. , Zhang, J. W. , Zang, G. Y. , and Pu, J. (2019). Never-ending learning. J. Geriatr.
Cardiol. 16(8), 585–591.
Krittanawong, C. , Zhang, H. , Wang, Z. , Aydar, M. , and Kitai, T. (2017). Artificial intelligence in
precision cardiovascular medicine. J. Am. Coll. Cardiol. 69(21), 2657–2664.
Samad, M. D. , Ulloa, A. , Wehner, G. J. , Jing, L. , Hartzel, D. , Good, C. W. , Williams, B. A. ,
Haggerty, C. M. and Fornwalt, B. K. (2019). Predicting survival from large echocardiography
and electronic health record datasets: optimization with machine learning. JACC Cardiovasc.
Imaging 12(4), 681–689.
Huang, S. , Yang, J. , Fong, S. , and Zhao, Q. (2020). Artificial intelligence in cancer diagnosis
and prognosis: Opportunities and challenges. Cancer Lett. 471, 61–71.
Obermeyer, Z. , and Emanuel, E. J. (2016). Predicting the future—big data, machine learning,
and clinical medicine. N. Engl. J. Med. 375(13), 1216–1219.
Bi, W. L. , Hosny, A. , Schabath, M. B. , Giger, M. L. , Birkbak, N. J. , Mehrtash, A. , Allison, T. ,
Arnaout, O. , Abbosh, C. , Dunn, I. F. , and Mak, R. H. (2019). Artificial intelligence in cancer
imaging: clinical challenges and applications. CA Cancer J. Clin. 69(2), 127–157.
McGranahan, N. , and Swanton, C. (2017). Clonal heterogeneity and tumor evolution: past,
present, and the future. Cell 168(4), 613–628.
Li, X. , Zhang, S. , Zhang, Q. , Wei, X. , Pan, Y. , Zhao, J. , Xin, X. , Qin, C. , Wang, X. , Li, J. ,
and Yang, F. (2019). Diagnosis of thyroid cancer using deep convolutional neural network
models applied to sonographic images: a retrospective, multicohort, diagnostic study. Lancet
Oncol. 20(2), 193–201.
Kar, D. , and Halder, S. (2019). Early Detection of Brain Tumor by Using K-Means Clustering,
Convolutional Neural Network and Support Vector Machine without any Imaging Test. In 2019
International Conference on Information Technology (ICIT) (pp. 59–64). IEEE.
Zhang, Y. , Jiang, B. , Zhang, L. , Greuter, M. J. , de Boc, G. H. , Zhang, H. , and Xie, X. (2022).
Lung nodule detectability of artificial intelligenceassisted CT image reading in lung cancer
screening. Artificial Intelligence 18(3), 327–334.
Rainey, C. , McConnell, J. , Hughes, C. , Bond, R. , and McFadden, S. (2021). Artificial
Intelligence for diagnosis of fractures on plain radiographs: a scoping review of current
literature. Intelligence-Based Medicine 5.
https://healthitanalytics.com/news/usingartificialintelligencetoidentifyfractures-on-x-rays
Voelker, R. (2018). Diagnosing fractures with AI. Jama 320(1), 23–23.
Murata, K. , Endo, K. , Aihara, T. , Suzuki, H. , Sawaji, Y. , Matsuoka, Y. , Nishimura, H. ,
Takamatsu, T. , Konishi, T. , Maekawa, A. , and Yamauchi, H. (2020). Artificial intelligence for
the detection of vertebral fractures on plain spinal radiography. Sci. Rep. 10(1), 1–8.
Xiong, Y. , Ba, X. , Hou, A. , Zhang, K. , Chen, L. , and Li, T. (2018). Automatic detection of
mycobacterium tuberculosis using artificial intelligence. J. Thorac. Dis. 10(3), 1936–1940.
Qin, Z. Z. , Sander, M. S. , Rai, B. , Titahong, C. N. , Sudrungrot, S. , Laah, S. N. , Adhikari, L.
M. , Carter, E. J. , Puri, L. , Codlin, A. J. , and Creswell, J. (2019). Using artificial intelligence to
read chest radiographs for tuberculosis detection: A multi-site evaluation of the diagnostic
accuracy of three deep learning systems. Sci. Rep. 9(1), 1–10.
Jamal, S. , Khubaib, M. , Gangwar, R. , Grover, S. , Grover, A. , and Hasnain, S. E. (2020).
Artificial Intelligence and Machine learning based prediction of resistant and susceptible
mutations in Mycobacterium tuberculosis. Sci. Rep. 10(1), 1–16.
Singla, R. , Singla, A. , Gupta, Y. , and Kalra, S. (2019). Artificial intelligence/machine learning
in diabetes care. Indian J. Endocrinol. Metab. 23(4), 495–497.
Ellahham, S. (2020). Artificial intelligence: the future for diabetes care. Am. J. Med. 133(8),
895–900.
Dankwa-Mullan, I. , Rivo, M. , Sepulveda, M. , Park, Y. , Snowdon, J. , and Rhee, K. (2019).
Transforming diabetes care through artificial intelligence: the future is here. Popul. Health
Manag. 22(3), 229–242.
Soun, J. E. , Chow, D. S. , Nagamine, M. , Takhtawala, R. S. , Filippi, C. G. , Yu, W. , and
Chang, P. D. (2021). Artificial intelligence and acute stroke imaging. Am. J. Neuroradiol. 42(1),
2–11.
Ding, L. , Liu, C. , Li, Z. , and Wang, Y. (2020). Incorporating artificial intelligence into stroke
care and research. Stroke, 51(12), 351–354.
Murray, N. M. , Unberath, M. , Hager, G. D. , and Hui, F. K. (2020). Artificial intelligence to
diagnose ischemic stroke and identify large vessel occlusions: a systematic review. J.
Neurointerv. Surg. 12(2), 156–164.
De, A. , Sarda, A. , Gupta, S. , and Das, S. (2020). Use of artificial intelligence in dermatology.
Indian J. Dermatol. 65(5), 352–357.
De Guzman, L. C. , Maglaque, R. P. C. , Torres, V. M. B. , Zapido, S. P. A. , and Cordel, M. O. ,
2015, December. Design and evaluation of a multi-model, multi-level artificial neural network for
eczema skin lesion detection. In 2015 3rd International conference on artificial intelligence,
modelling and simulation (AIMS) (pp. 42–47). IEEE.
Shrivastava, V. K. , Londhe, N. D. , Sonawane, R. S. , and Suri, J. S. (2017). A novel and robust
Bayesian approach for segmentation of psoriasis lesions and its risk stratification. Comput.
Methods Programs Biomed. 150, 9–22.
Scannell, J. W. , Blanckley, A. , Boldon, H. , and Warrington, B. (2012). Diagnosing the decline
in pharmaceutical R&D efficiency. Nat. Rev. Drug Discov. 11, 191−200.
DiMasi, J. A. , Grabowski, H. G. , and Hansen, R. W. (2016). Innovation in the pharmaceutical
industry: New estimates of R&D costs. J. Health Econ. 47, 20−33.
Zhavoronkov, A. , Ivanenkov, Y. A. , Aliper, A. , Veselov, M. S. , Aladinskiy, V. A. , Aladinskaya,
A. V. , Terentiev, V. A. , Polykovskiy, D. A. , Kuznetsov, M. D. , Asadulaev, A. , and Volkov, Y.
(2019). Deep learning enables rapid identification of potent DDR1 kinase inhibitors. Nat.
Biotechnol. 37(9), 1038–1040.
Walters, W. P. , and Murcko, M. (2020). Assessing the impact of generative AI on medicinal
chemistry. Nat. Biotechnol. 38, 143−145.
Paul, S. M. , Mytelka, D. S. , Dunwiddie, C. T. , Persinger, C. C. , Munos, B. H. , Lindborg, S. R.
, and Schacht, A. L. (2010). How to improve R&D productivity: the pharmaceutical industry’s
grand challenge. Nat. Rev. Drug Discov. 9(3), 203–214.
Lamberti, M. J. (2019). A study on the application and use of artificial intelligence to support
drug development. Clin. Ther. 41, 1414–1426.
https://hbr.org/2017/06/if-your-company-isnt-goodat-analytics-its-notready-for-ai
Kaitin, K. I. (2019). Artificial intelligence and patient-centric approaches to advance
pharmaceutical innovation. Clin. Ther. 41(8), 1406–1407.
www.mckinsey.com/industries/retail/our-insights/how-retailers-cankeep-up-with-consumers
https://hbr.org/2016/11/what-artificial-intelligencecan-and-cant-doright-now
https://renci.org/wp-content/uploads/2015/11/SCi-Discovery-BigDataFINAL-11.23.15.pdf
https://hbr.org/2018/12/why-companies-that-waitto-adopt-ai-maynever-catch-up
Davenport T. H. , and Ronanki R. (2018). Artificial intelligence for the real world. Harvard Bus.
Rev. 96, 108–116.
Use of Artificial Intelligence and Robotics: Making the Drug
Development Process Easier
Paul, D. , Sanap, G. , Shenoy, S. , Kalyane, D. , Kalia, K. and Tekade, R. K. , 2021. Artificial
intelligence in drug discovery and development. Drug Discovery Today, 26(1), p.80.
Blasiak, A. , Khong, J. and Kee, T. , 2020. CURATE. AI: optimizing personalized medicine with
artificial intelligence. SLAS TECHNOLOGY: Translating Life Sciences Innovation, 25(2),
pp.95–105.
Mak K.-K. , Pichika M. R. Artificial intelligence in drug development: present status and future
prospects. Drug Discovery Today. 2019;24:773–780.
Sellwood, M. A. , Ahmed, M. , Segler, M. H. and Brown, N. , 2018. Artificial intelligence in drug
discovery. Future medicinal chemistry, 10(17), pp.2025–2028.
Zhu H. Big data and artificial intelligence modeling for drug discovery. Annu. Rev. Pharmacol.
Toxicol. 2020;60:573–589.
Ciallella H. L. , Zhu H. Advancing computational toxicology in the big data era by artificial
intelligence: data-driven and mechanism-driven modeling for chemical toxicity. Chem. Res.
Toxicol. 2019;32:536–547.
Zang, Q. , Mansouri, K. , Williams, A. J. , Judson, R. S. , Allen, D. G. , Casey, W. M. and
Kleinstreuer, N. C. , 2017. In silico prediction of physicochemical properties of environmental
chemicals using molecular fingerprints and machine learning. Journal of chemical information
and modeling, 57(1), pp.36–49.
Yang, X. , Wang, Y. , Byrne, R. , Schneider, G. and Yang, S. , 2019. Concepts of artificial
intelligence for computer-assisted drug discovery. Chemical reviews, 119(18), pp.10520–10594.
Hessler, G. and Baringhaus, K. H. , 2018. Artificial intelligence in drug design. Molecules,
23(10), p.2520.
Ramesh, A. N. , Kambhampati, C. , Monson, J. R. and Drew, P. J. , 2004. Artificial intelligence
in medicine. Annals of the Royal College of Surgeons of England, 86(5), p.334.
https://github.com/deepchem/deepchem
http://www.bioinf.jku.at/research/DeepTox
https://github.com/Merck/DeepNeuralNet-QSAR
https://pubs.acs.org/doi/full/10.1021/acscentsci.8b00507
http://hitdexter2.zbh.uni-hamburg.de/
https://zenodo.org/record/1481731
https://deepmind.com/blog/alphafold
http://refhub.elsevier.com/S0016-5107(20)34466-7/sref1
http://refhub.elsevier.com/S0016-5107(20)34466-7/sref2
http://refhub.elsevier.com/S0016-5107(20)34466-7/sref7
http://refhub.elsevier.com/S0016-5107(20)34466-7/sref8
http://refhub.elsevier.com/S0016-5107(20)34466-7/sref10
http://refhub.elsevier.com/S0016-5107(20)34466-7/sref14
http://refhub.elsevier.com/S0016-5107(20)34466-7/sref16
Piñero, J. , Ramírez-Anguita, J. M. , Saüch-Pitarch, J. , Ronzano, F. , Centeno, E. , Sanz, F.
and Furlong, L. I. , 2020. The DisGeNET knowledge platform for disease genomics: 2019
update. Nucleic acids research, 48(D1), pp.D845–D855.
Vasaikar, S. V. , P. Straub , J. Wang , and B. Zhang (2018) LinkedOmics: analyzing multi-omics
data within and across 32 cancer types. Nucleic Acids Res. 46: D956–D963.
Meyers, R. M. , Bryan, J. G. , McFarland, J. M. , Weir, B. A. , Sizemore, A. E. , Xu, H. , Dharia,
N. V. , Montgomery, P. G. , Cowley, G. S. , Pantel, S. and Goodale, A. , 2017. Computational
correction of copy number effect improves specificity of CRISPR–Cas9 essentiality screens in
cancer cells. Nature genetics, 49(12), pp.1779–1784.
Tsherniak, A. , F. Vazquez , P. G. Montgomery , B. A. Weir , G. Kryukov , G. S. Cowley , S. Gill
, W. F. Harrington , S. Pantel , J. M. Krill-Burger , R. M. Meyers , L. Ali , A. Goodale , Y. Lee , G.
Jiang , J. Hsiao , W. F. J. Gerath , S. Howell , E. Merkel , M. Ghandi , L. A. Garraway , D. E.
Root , T. R. Golub , J. S. Boehm , and W. C. Hahn (2017) Defining a cancer dependency map.
Cell. 170: 564–576.e16.
Wang, Y. , S. Zhang , F. Li , Y. Zhou , Y. Zhang , Z. Wang , R. Zhang , J. Zhu , Y. Ren , Y. Tan ,
C. Qin , Y. Li , X. Li , Y. Chen , and F. Zhu (2020) Therapeutic target database 2020: enriched
resource for facilitating research and early development of targeted therapeutics. Nucleic Acids
Res. 48: D1031–D1041.
Camarillo, D. B. , Krummel, T. M. and Salisbury Jr, J. K. , 2004. Robotic technology in surgery:
past, present, and future. The American Journal of Surgery, 188(4), pp.2–15.
A robot with improved absolute positioning accuracy for CT guided stereotactic brain surgery.
Kwoh YS, Hou J, Jonckheere EA, Hayati SIEEE Trans Biomed Eng. 1988 Feb; 35(2):153–160.
Beasley, R. A. , 2012. Medical robots: current systems and research directions. Journal of
Robotics, 2012.
Song, E. K. and Seon, J. K. , 2012. Computer assisted orthopedic surgery in TKA. Recent
Advances in Hip and Knee Arthroplasty.
http://surgrob.blogspot.com/2008/12/integrated-surgical-systemsinc.html
M. Hoeckelmann , I. Rudas , P. Fiorini , F. Kirchner , and T. Haidegger , “Current capabilities
and development potential in surgical robotics,” International Journal of Advanced Robotic
Systems, vol. 12, no. 5, p. 61, 2015.
F. Pugin , P. Bucher , and P. Morel , “History of robotic surgery: from AESOP and ZEUS to da
Vinci,” Journal of Visceral Surgery, vol. 148, no. 5, pp. e3–e8, 2011.
M. Hoeckelmann , I. Rudas , P. Fiorini , F. Kirchner , and T. Haidegger , “Current capabilities
and development potential in surgical robotics,” International Journal of Advanced Robotic
Systems, vol. 12, no. 5, p. 61, 2015.
I. Gibbs , “Frameless image-guided intracranial and extracranial radiosurgery using the
Cyberknife™ robotic system,” Cancer/Radiothérapie, vol. 10, no. 5, pp. 283–287, 2006.
W. Siebert , S. Mai , R. Kober , and P. Heeckt , “Technique and first clinical results of robot-
assisted total knee replacement,” The Knee, vol. 9, no. 3, pp. 173–180, 2002.
K. Cleary , A. Melzer , V. Watson , G. Kronreif , and D. Stoianovici , “Interventional robotic
systems: applications and technology state of the art,” Minimally Invasive Therapy & Allied
Technologies, vol. 15, no. 2, pp. 101–113, 2006.
D. Stoianovici , K. Cleary , A. Patriciu et al. , “Acubot: a robot for radiological interventions,”
IEEE Transactions on Robotics and Automation, vol. 19, no. 5, pp. 927–930, 2003.
M. Bucolo , A. Buscarino , A. Spinosa , G. Stella , and L. Fortuna , “Human machine models for
remote control of ultrasound scan equipment,” in Proceedings of the IEEE International
Conference on HumanMachine Systems (ICHMS), pp. 1–6, Rome, Italy, April 2020.
J. Kettenbach and G. Kronreif , “Robotic systems for percutaneous needle-guided
interventions,” Minimally Invasive Therapy & Allied Technologies, vol. 24, no. 1, pp. 45–53,
2014.
M. Lefranc and J. Peltier , “Evaluation of the ROSA™ Spine robot for minimally invasive surgical
procedures,” Expert Review of Medical Devices, vol. 13, no. 10, pp. 899–906, 2016.
https://www.zimmerbiomet.com/en/products-and-solutions/zbedge/robotics/rosa-brain.html
D. Maberley , M. Beelen , J. Smit et al. , “A comparison of robotic and manual surgery for
internal limiting membrane peeling,” Graefe’s Archive for Clinical and Experimental
Ophthalmology, vol. 258, no. 4, pp. 773–778, 2020.
Dogangil, G. , Davies, B. L. , & Rodriguez y Baena, F. (2010). A review of medical roboticsfor
minimally invasive soft tissue surgery. Proceedings of the Institution of Mechanical Engineers.
Part H, Journal of Engineering in Medicine, 224(5), 653–679. doi:
10.1243/09544119JEIM591PMID:20718269
Beasley, R. A. (2012). Medical robots: Current systems and research directions. Journal of
Robotics, 2012, 1–14. doi: 10.1155/2012/401613
Schulz, A. P. , Seide, K. , Queitsch, C. , von Haugwitz, A. , Meiners, J. , Kienast, B. , & Jürgens,
C. et al. (2007). Results of total hip replacement using the Robodoc surgical assistant system:
Clinical outcome and evaluation of complications for 97 procedures. International Journal of
Medical Robotics and Computer Assisted Surgery, 3(4), 301–306. doi:
10.1002/rcs.161PMID:18000945
Ballantyne, G. H. (2002). Robotic surgery, telerobotic surgery, telepresence, and telementoring.
Surgical Endoscopy, 16(10), 1389–1402. doi: 10.1007/s00464-001-8283-7PMID:12140630
Stark, M. , Benhidjeb, T. , Gidaro, S. and Morales, E. R. , 2012. The future of telesurgery: a
universal system with haptic sensation. Journal of the Turkish German Gynecological
Association, 13(1), p.74.
Gomes, P. , 2011. Surgical robotics: Reviewing the past, analysing the present, imagining the
future. Robotics and Computer-Integrated Manufacturing, 27(2), pp.261–266.
https://www.zs.com/insights/is-data-science-the-treatment-forinefficiencies-in-clinical-trial-
operations
Deore, A. B. , Dhumane, J. R. , Wagh, R. and Sonawane, R. , 2019. The stages of drug
discovery and development process. Asian Journal of Pharmaceutical Research and
Development, 7(6), pp.62–67.
Costa, G. G. , Cardoso, K. C. , Del Bem, L. E. , Lima, A. C. , Cunha, M. A. , de Campos-Leite,
L. , Vicentini, R. , Papes, F. , Moreira, R. C. , Yunes, J. A. and Campos, F. A. , 2010.
Transcriptome analysis of the oil-rich seed of the bioenergy crop Jatropha curcas L. BMC
genomics, 11(1), pp.1–9.
Winkler, H. , 2003. Target validation requirements in the pharmaceutical industry. Targets, 2(3),
pp.69–71.
Hutson, M. , 2019. AI protein-folding algorithms solve structures faster than ever. Nature.
Bhatt, T. K. and Nimesh, S . eds., 2021. The Design and Development of Novel Drugs and
Vaccines: Principles and Protocols. Academic Press.
Pound, P. and Ritskes-Hoitinga, M. , 2018. Is it possible to overcome issues of external validity
in preclinical animal research? Why most animal models are bound to fail. Journal of
translational medicine, 16(1), pp.1–8.
Bender, A. and Cortés-Ciriano, I. , 2021. Artificial intelligence in drug discovery: what is realistic,
what are illusions? Part 1: ways to make an impact, and why we are not there yet. Drug
discovery today, 26(2), pp.511–524.
Schneider, G. and Clark, D. E. , 2019. Angew. Chem. Int. Ed., 58, pp.10792–10803.
Singh, A. V. , Ansari, M. H. D. , Laux, P. and Luch, A. , 2019. Micronanorobots: important
considerations when developing novel drug delivery platforms. Expert opinion on drug delivery,
16(11), pp.12591275.
Li, J. , de Ávila, B. E. F. , Gao, W. , Zhang, L. and Wang, J. , 2017. Micro/nanorobots for
biomedicine: Delivery, surgery, sensing, and detoxification. Science Robotics, 2(4).
Felfoul, O. , Mohammadi, M. , Taherkhani, S. , De Lanauze, D. , Xu, Y. Z. , Loghin, D. , Essa, S.
, Jancik, S. , Houle, D. , Lafleur, M. and Gaboury, L. , 2016. Magneto-aerotactic bacteria deliver
drug-containing nanoliposomes to tumour hypoxic regions. Nature nanotechnology, 11(11),
pp.941–947.
Li, J. , de Ávila, B. E. F. , Gao, W. , Zhang, L. and Wang, J. , 2017. Micro/nanorobots for
biomedicine: Delivery, surgery, sensing, and detoxification. Science Robotics, 2(4).
Wang, W. , Li, S. , Mair, L. , Ahmed, S. , Huang, T. J. and Mallouk, T. E. , 2014. Acoustic
propulsion of nanorod motors inside living cells. Angewandte Chemie International Edition,
53(12), pp.3201–3204.
Kei Cheang, U. , Lee, K. , Julius, A. A. and Kim, M. J. , 2014. Multiplerobot drug delivery
strategy through coordinated teams of microswimmers. Applied physics letters, 105(8),
p.083705.
da Silva Luz, G. V. , Barros, K. V. G. , de Araújo, F. V. C. , da Silva, G. B. , da Silva, P. A. F. ,
Condori, R. C. I. and Mattos, L. , 2016. Nanorobotics in drug delivery systems for treatment of
cancer: a review. J Mat Sci Eng A, 6, pp.167–180.
Hussan Reza, K. , Asiwarya, G. , Radhika, G. and Bardalai, D. , 2011. Nanorobots: The future
Trend of Drug Delivery and Therapeutics. International Journal of Pharmaceutical Sciences
Review and Research, 10(1), pp.60–68.
Freitas Jr, R. A. , 2009. Medical Nanorobotics: The Long-Term Goal for Nanomedicine.
Nanomedicine design of particles, sensors, motors, implants, robots and devices. Artech
House, Norwood Ma, pp.367–392.
Tewabe, A. , Abate, A. , Tamrie, M. , Seyfu, A. and Siraj, E. A. , 2021. Targeted drug
delivery—from magic bullet to nanomedicine: Principles, challenges, and future perspectives.
Journal of Multidisciplinary Healthcare, 14, p.1711.
Freitas, R. A. , 2006. Pharmacytes: An ideal vehicle for targeted drug delivery. Journal of
Nanoscience and Nanotechnology, 6(9–10), pp.2769–2775.
Hariharan, R. and Manohar, J. , 2010, December. Nanorobotics as medicament:(Perfect
solution for cancer). In Interact-2010 (pp. 4–7). IEEE.
Sandhiya, S. , Dkhar, S. A. and Surendiran, A. , 2009. Emerging trends of nanomedicine–an
overview. Fundamental & clinical pharmacology, 23(3), pp.263–269.
Chaudhari, P. M. and Shekokare, H. L. , PHARMACEUTICAL SCIENCES.
Eshaghian-Wilner, M. M. ed., 2009. Bio-inspired and nanoscale integrated computing (Vol. 1).
John Wiley & Sons.
Hassanzadeh, P. , Atyabi, F. and Dinarvand, R. , 2019. The significance of artificial intelligence
in drug delivery system design. Advanced drug delivery reviews, 151, pp.169–190.
Colombo, S. , 2020. Applications of artificial intelligence in drug delivery and pharmaceutical
development. In Artificial Intelligence in Healthcare (pp. 85–116). Academic Press.
https://www.santannapisa.it/en/news/implantable-robots-and-magneticcapsules-diabetes-
treatment-study-published-science-robotics
Alfonta, L. , 2021. Bioelectrochemistry and the Singularity Point “I Robot”?. Israel Journal of
Chemistry, 61(1–2), pp.60–67.
https://www.emergency-live.com/news/implantable-robots-andmagnetic-capsules-the-new-
frontier-of-insulin-infusion-in-diabetics/
Paul, D. , Sanap, G. , Shenoy, S. , Kalyane, D. , Kalia, K. and Tekade, R. K. , 2021. Artificial
intelligence in drug discovery and development. Drug Discovery Today, 26(1), p.80.
Tsigelny, I. F. , 2019. Artificial intelligence in drug combination therapy. Briefings in
bioinformatics, 20(4), pp.1434–1448.
Li, X. , Xu, Y. , Cui, H. , Huang, T. , Wang, D. , Lian, B. , Li, W. , Qin, G. , Chen, L. and Xie, L. ,
2017. Prediction of synergistic anti-cancer drug combinations based on drug target network and
drug induced gene expression profiles. Artificial intelligence in medicine, 83, pp.35–43.
Patel, G. M. , Patel, G. C. , Patel, R. B. , Patel, J. K. and Patel, M. , 2006. Nanorobot: a versatile
tool in nanomedicine. Journal of drug targeting, 14(2), pp.63–67.
Richardson, J. J. and Caruso, F. , 2020. Nanomedicine toward 2040. Nano letters, 20(3),
pp.1481–1482.
Rifaioglu, A. S. , Atas, H. , Martin, M. J. , Cetin-Atalay, R. , Atalay, V. and Dogan, T. , 2019.
Recent applications of deep learning and˘ machine intelligence on in silico drug discovery:
methods, tools and databases. Briefings in bioinformatics, 20(5), pp.1878–1912.
Arora, K. and Bist, A. S. , 2020. Artificial intelligence based drug discovery techniques for covid-
19 detection. Aptisi Transactions On Technopreneurship (ATT), 2(2), pp.120–126.
Minnich, A. J. , McLoughlin, K. , Tse, M. , Deng, J. , Weber, A. , Murad, N. , Madej, B. D. ,
Ramsundar, B. , Rush, T. , Calad-Thomson, S. and Brase, J. , 2020. AMPL: a data-driven
modeling pipeline for drug discovery. Journal of chemical information and modeling, 60(4),
pp.19551968.
Ma, J. , Sheridan, R. P. , Liaw, A. , Dahl, G. E. and Svetnik, V. , 2015. Deep neural nets as a
method for quantitative structure–activity relationships. Journal of chemical information and
modeling, 55(2), pp.263–274.
Xu, Y. , 2022. Deep Neural Networks for QSAR. In Artificial Intelligence in Drug Design (pp.
233–260). Humana, New York, NY.
Hu, S. , Chen, P. , Gu, P. and Wang, B. , 2020. A deep learning-based chemical system for
QSAR prediction. IEEE journal of biomedical and health informatics, 24(10), pp.3020–3028.
Mayr, A. , Klambauer, G. , Unterthiner, T. and Hochreiter, S. , 2016. DeepTox: toxicity prediction
using deep learning. Frontiers in Environmental Science, 3, p.80.
Batool, M. , Ahmad, B. and Choi, S. , 2019. A structure-based drug discovery paradigm.
International journal of molecular sciences, 20(11), p.2783.
Yang, X. , Wang, Y. , Byrne, R. , Schneider, G. and Yang, S. , 2019. Concepts of artificial
intelligence for computer-assisted drug discovery. Chemical reviews, 119(18), pp.10520–10594.
Zhao, L. , Ciallella, H. L. , Aleksunes, L. M. and Zhu, H. , 2020. Advancing computer-aided drug
discovery (CADD) by big data and data-driven machine learning modeling. Drug discovery
today.
Jiang, D. , Wu, Z. , Hsieh, C. Y. , Chen, G. , Liao, B. , Wang, Z. , Shen, C. , Cao, D. , Wu, J. and
Hou, T. , 2021. Could graph neural networks learn better molecular representation for drug
discovery? A comparison study of descriptor-based and graph-based models. Journal of
cheminformatics, 13(1), pp.1–23.
Han, K. , Lakshminarayanan, B. and Liu, J. , 2021. Reliable Graph Neural Networks for Drug
Discovery Under Distributional Shift. arXiv preprint arXiv:2111.12951.
Feinberg, E. N. , Sur, D. , Wu, Z. , Husic, B. E. , Mai, H. , Li, Y. , Sun, S. , Yang, J. ,
Ramsundar, B. and Pande, V. S. , 2018. PotentialNet for molecular property prediction. ACS
central science, 4(11), pp.15201530.
https://medium.com/@pandelab/step-change-improvement-inmolecular-property-prediction-
with-potentialnet-f431ffa32a2c
Correia, J. , Resende, T. , Baptista, D. and Rocha, M. , 2019, June. Artificial intelligence in
biological activity prediction. In International Conference on Practical Applications of
Computational Biology & Bioinformatics (pp. 164–172). Springer, Cham.
Pérez Santín, E. , Rodríguez Solana, R. , González García, M. , García Suárez, M. D. M. ,
Blanco Díaz, G. D. , Cima Cabal, M. D. , Moreno Rojas, J. M. and López Sánchez, J. I. , 2021.
Toxicity prediction based on artificial intelligence: A multidisciplinary overview. Wiley
Interdisciplinary Reviews: Computational Molecular Science, p.e1516.
Zang, Q. , Mansouri, K. , Williams, A. J. , Judson, R. S. , Allen, D. G. , Casey, W. M. and
Kleinstreuer, N. C. , 2017. In silico prediction of physicochemical properties of environmental
chemicals using molecular fingerprints and machine learning. Journal of chemical information
and modeling, 57(1), pp.36–49.
Jordan, A. M. , 2018. Artificial intelligence in drug design—the storm before the calm?. ACS
medicinal chemistry letters, 9(12), pp.1150–1152.
Arabi, A. A. , 2021. Artificial intelligence in drug design: algorithms, applications, challenges and
ethics. Future Drug Discovery, (0), p.FDD59.
Tanoli, Z. , Vähä-Koskela, M. and Aittokallio, T. , 2021. Artificial intelligence, machine learning,
and drug repurposing in cancer. Expert opinion on drug discovery, pp.1–13.
Selvaraj, G. , Kaliamurthi, S. , Peslherbe, G. H. and Wei, D. Q. , Application of Artificial
Intelligence in Drug Repurposing: A Mini-Review.
Chaudhari, R. , Fong, L. W. , Tan, Z. , Huang, B. and Zhang, S. , 2020. An up-to-date overview
of computational polypharmacology in modern drug discovery. Expert opinion on drug
discovery, 15(9), pp.1025–1044.
Li, Z. , Li, X. , Liu, X. , Fu, Z. , Xiong, Z. , Wu, X. , Tan, X. , Zhao, J. , Zhong, F. , Wan, X. and
Luo, X. , 2019. KinomeX: a web application for predicting kinome-wide polypharmacology effect
of small molecules. Bioinformatics, 35(24), pp.5354–5356.

Pharmaceutical Packaging: New Impulse through Artificial Intelligence

Kondapi, D. (2022, March 16). Pharmaceutical packaging: How automation & digitization have
influence. https://www.industr.com/en/pharmaceutical-packaging-how-automation-digitisation-
have-influence-2645258
Girshick, R. , Donahue, J. , Darrell, T. , & Malik, J. (2014). RCNN: Regions with CNN features.
Proceedings of the Ieee Conference on Computer Vision and Pattern Recognition.
http://gwylab.com/pdf/rcnn_chs.pdf
Gross, A. (202 CE, February 13). How AI can keep pharma safe - European Pharmaceutical
Manufacturer. European Pharmaceutical Manufacturer.
https://pharmaceuticalmanufacturer.media/pharmaceutical-industry-insights/how-ai-can/
Girshick, R. , Donahue, J. , Darrell, T. , & Malik, J. (2013a). Rich feature hierarchies for accurate
object detection and semantic segmentation. Proceedings of the IEEE Computer Society
Conference on Computer Vision and Pattern Recognition, 580–587.
https://doi.org/10.48550/arxiv.1311.2524
[1311.2524] Rich Feature Hierarchies for Accurate Object Detection and Semantic
Segmentation. (n.d.). Retrieved April 19, 2022, from https://arxiv.org/abs/1311.2524
Yousefi, H. , Su, H. M. , Imani, S. M. , Alkhaldi, K. , Filipe, C. D. , & Didar, T. F. (2019).
Intelligent Food Packaging: A Review of Smart Sensing Technologies for Monitoring Food
Quality. ACS Sensors, 4(4), 808–821.
https://doi.org/10.1021/ACSSENSORS.9B00440/ASSET/IMAGES/MEDIUM/SE-2019-
00440B_0007.Gif
Zhang, H. , Wei, X. , Chan-Park, M. B. , & Wang, M. (2022). Colorimetric Sensors Based on
Multifunctional Polymers for Highly Sensitive Detection of Food Spoilage. ACS Food Science &
Technology, 2(4), 703–711. https://doi.org/10.1021/ACSFOODSCITECH.2C00019
Pharmaceutical Trend in 2019: New Impulses Through Artificial Intelligence – Interpack. (n.d.).
Retrieved April 1, 2022, from
https://www.interpack.com/en/Discover/TIGHTLY_PACKED_Magazine/PHARMACEUTICS_PA
CKAGING/News/Pharmaceutical_Trend_in_2019_New_Impulses_through_Artificial_Intelligenc
e
Zhu, Y. , Li, G. , Wang, R. , Tang, S. , Su, H. , & Cao, K. (2021a). Intelligent fault diagnosis of
hydraulic piston pump combining improved LeNet-5 and PSO hyperparameter optimization.
Applied Acoustics, 183. https://doi.org/10.1016/J.APACOUST.2021.108336
Essid, O. , Laga, H. , & Samir, C. (2018). Automatic detection and classification of
manufacturing defects in metal boxes using deep neural networks. Plos One, 13(11), e0203192.
https://doi.org/10.1371/JOURNAL.PONE.0203192
Sa, J. , Li, Z. , Yang, Q. , & Chen, X. (2020). Packaging defect detection system based on
machine vision and deep learning. 2020 5th International Conference on Computer and
Communication Systems, ICCC
Hajizadeh, S. , Núñez, A. , & Tax, D. M. J. (2016). Semi-supervised Rail Defect Detection from
Imbalanced Image Data. IFAC-Papers Online, 49(3), 78–83.
https://doi.org/10.1016/J.IFACOL.2016.07.014
Zhong, G. , Wang, L. N. , Ling, X. , & Dong, J. (2016). An overview on data representation
learning: From traditional feature learning to recent deep learning. Journal of Finance and Data
Science, 2(4), 265–278. ht tps://doi.org/10.1016/J.JFDS.2017.05.001
Liu, Y. , Chen, S. , Tinglong, T. , & Zhao, M. (2017a). Defect inspection of medicine vials using
LBP features and SVM classifier. 2017 2nd International Conference on Image, Vision and
Computing, ICIVC 2017, 41–45. https://doi.org/10.1109/ICIVC.2017.7984515
Defect Inspection of Medicine Vials Using LBP Features and SVM Classifier | Semantic
Scholar. (n.d.). Retrieved April 19, 2022, from https://www.semanticscholar.org/paper/Defect-
inspection-of-medicine-vials-using-LBP-and-Liu-
Chen/436a612c17a470cfd82a8d3a4b10c1658fd8c51a
Liu, Y. , Chen, S. , Tinglong, T. , & Zhao, M. (2017b). Defect inspection of medicine vials using
LBP features and SVM classifier. 2017 2nd International Conference on Image, Vision and
Computing, ICIVC 2017, 41–45. https://doi.org/10.1109/ICIVC.2017.7984515
Feng, Y. , Tang, T. , & Chen, S. (2019). A Method of Penicillin Bottle Defect Inspection Based
on BP. Neural Network. Communications in Computer and Information Science, 1043, 31–40.
https://doi.org/10.1007/978-981-13-9917-6_4/FIGURES/12
Golnabi, H. , & Asadpour, A. (2007). Design and application of industrial machine vision
systems. Robotics and Computer-Integrated Manufacturing, 23(6), 630–637.
https://doi.org/10.1016/J.RCIM.2007.02.005
Wu, Y. , & Lu, Y. (2019). An intelligent machine vision system for detecting surface defects on
packing boxes based on support vector machine. Measurement and Control (United Kingdom),
52(7–8), 1102–1110. https://doi.org/10.1177/0020294019858175
Bahaghighat, M. , Akbari, L. , & Xin, Q. (2019). A machine learning based approach for counting
blister cards within drug packages. IEEE Access, 7, 83785–83796.
https://doi.org/10.1109/ACCESS.2019.2924445
Orun, A. , & Smith, G. (2017). Micro-Structural Analysis of Tablet Surface Layers by Intelligent
Laser Speckle Classification (ILSC) Technique: an Application in the Study of both Surface
Defects and Subsurface Granule Structures. Journal of Pharmaceutical Innovation, 12(4),
296–308. https://doi.org/10.1007/S12247-017-9290-0/FIGURES/10
Yost, E. , Chalus, P. , Zhang, S. , Peter, S. , & Narang, A. S. (2019). Quantitative X-Ray
Microcomputed Tomography Assessment of Internal Tablet Defects. Journal of Pharmaceutical
Sciences, 108(5), 1818–1830. https://doi.org/10.1016/J.XPHS.2018.12.024
Sheng, Z. , & Wang, G. (2022a). Fast Method of Detecting Packaging Bottle Defects Based on
ECA-EfficientDet. Journal of Sensors, 2022. https://doi.org/10.1155/2022/9518910
Marques, G. , Agarwal, D. , & de la Torre Díez, I. (2020). Automated medical diagnosis of
COVID-19 through EfficientNet convolutional neural network. Applied Soft Computing Journal,
96. https://doi.org/10.1016/J.ASOC.2020.106691
van der Wal, D. , Jhun, I. , Laklouk, I. , Nirschl, J. , Richer, L. , Rojansky, R. , Theparee, T. ,
Wheeler, J. , Sander, J. , Feng, F. , Mohamad, O. , Savarese, S. , Socher, R. , & Esteva, A.
(2021). Biological data annotation via a human-augmenting AI-based labeling system. Npj
Digital Medicine 2021 4:1, 4(1), 1–7. https://doi.org/10.1038/s41746-021-00520-6
Lecun, Y. , Bengio, Y. , & Hinton, G. (2015). Deep learning. Nature, 521(7553), 436–444.
https://doi.org/10.1038/nature14539
Gong, Y. , Liu, L. , Yang, M. , & Bourdev, L. (2014a). Compressing Deep Convolutional
Networks using Vector Quantization. https://doi.org/10.48550/arxiv.1412.6115
Ramachandran, P. , Zoph, B. , & Le, Q. V. (2017a). Searching for Activation Functions.
http://arxiv.org/abs/1710.05941
Sheng, Z. , & Wang, G. (2022a). Fast Method of Detecting Packaging Bottle Defects Based on
ECA-EfficientDet. Journal of Sensors, 2022. https://doi.org/10.1155/2022/9518910
Sa, J. , Li, Z. , Yang, Q. , & Chen, X. (2020). Packaging defect detection system based on
machine vision and deep learning. 2020 5th International Conference on Computer and
Communication Systems, Icccs 2020, 404–408.
https://doi.org/10.1109/ICCCS49078.2020.9118413
Introducing Deep Learning with MATLAB - MATLAB & Simulink. (n.d.). Retrieved April 19, 2022,
from https://in.mathworks.com/campaigns/offers/deep-learning-with-
matlab.html?ef_id=CjwKCAjwu_mSBhAYEiwA5BBmf-FDPbPb5-
IW2xTkFbA8z4pkB160lz8bX8EKOpLYSPq4XiECWAYWGxoCjVgQAvD_BwE:G:s&s_kwcid=AL
!8664!3!227584766104!b!!g!!%2Bconvolutional%20%2Bneural%20%2Bnetworks&s_eid=psn_4
5581054546&q=+convolutional%20+neural%20+networks&gclid=CjwKCAjwu_mSBhAYEiwA5B
Bmf-FDPbPb5-IW2xTkFbA8z4pkB160lz8bX8EKOpLYSPq4XiECWAYWGxoCjVgQAvD_BwE
Gong, Y. , Liu, L. , Yang, M. , & Bourdev, L. (2014b). Compressing Deep Convolutional
Networks using Vector Quantization http://arxiv.org/abs/1412.6115
Gong, Y. , Liu, L. , Yang, M. , & Bourdev, L. (2014a). Compressing Deep Convolutional
Networks using Vector Quantization. https://doi.org/10.48550/arxiv.1412.6115
Wang, Y. , Liu, M. , Zheng, P. , Yang, H. , & Zou, J. (2020). A smart surface inspection system
using faster R-CNN in cloud-edge computing environment. Advanced Engineering Informatics,
43, 101037. https://doi.org/10.1016/J.AEI.2020.101037
Misra, D. (2019). Mish: A Self Regularized Non-Monotonic Activation Function.
http://arxiv.org/abs/1908.08681
Sheng, Z. , & Wang, G. (2022b). Fast Method of Detecting Packaging Bottle Defects Based on
ECA-EfficientDet. Journal of Sensors, 2022. https://doi.org/10.1155/2022/9518910
Ramachandran, P. , Zoph, B. , & Le, Q. V. (2017b). Searching for Activation Functions.
http://arxiv.org/abs/1710.05941
Tsao, W.-C. , & Tu, Y.-H. (2017). 1137 I www.irmbrjournal . International Review of
Management and Business Research, 6, 3. www.irmbrjournal.com
Kwon, Y. J. , Kim, J. G. , Seo, J. , Lee, D. H. , & Kim, D. S. (2007). A tabu search algorithm
using the Voronoi diagram for the capacitated vehicle routing problem. Proceedings - The 2007
International Conference on Computational Science and Its Applications, ICCSA 2007,
480–485. ht tps://doi.org/10.1109/ICCSA.2007.86
(15) (PDF) Expert Robots for Automatic Packaging and Processing. (n.d.). Retrieved April 19,
2022, from https://www.researchgate.net/publication/236201867_Expert_robots_for_automatic-
packaging-and-processing
The QR-code Reorganization in Illegible Snapshots Taken by Mobile Phones | Semantic
Scholar. (n.d.). Retrieved April 19, 2022, from https://www.semanticscholar.org/paper/The-QR-
code-reorganization-in-illegible-snapshots-Sun-
Sun/72c84093173e5ddd27eeed7d94a206d006176a58
Zhu, Y. , Li, G. , Wang, R. , Tang, S. , Su, H. , & Cao, K. (2021b). Intelligent fault diagnosis of
hydraulic piston pump combining improveLeNet5 and PSO hyperparameter optimization.
Applied Acoustics, 183. https://doi.org/10.1016/J.APACOUST.2021.108336
Wang, Z. , Zhao, W. , Du, W. , Li, N. , & Wang, J. (2021). Datadriven fault diagnosis method
based on the conversion of erosion operation signals into images and convolutional neural
network. Process Safety and Environmental Protection, 149, 591–601.
https://doi.org/10.1016/J.PSEP.2021.03.016
Gao, Z. , Zhang, Y. , & Li, Y. (2020). Extracting features from infrared images using
convolutional neural networks and transfer learning infrared Physics and Technology, 105.
https://doi.org/10.1016/J.INFRARED.2020.103237
Krizhevsky, A. , Sutskever, I. , & Hinton, G. E. (2017). ImageNet classification with deep
convolutional neural networks. Communications of the ACM, 60(6), 84–90.
https://doi.org/10.1145/3065386
LeCun, Y. , Bottou, L. , Bengio, Y. , & Haffner, P. (1998). Gradient-based learning applied to
document recognition. Proceedings of the IEEE, 86(11), 2278–2323.
https://doi.org/10.1109/5.726791
Ramachandran, P. , Zoph, B. , & Le, Q. V. (2017c). Searching for Activation Functions.
http://arxiv.org/abs/1710.05941
Virtual Reality (VR) & Augmented Reality (AR) Technologies for Tourism and Hospitality
Industry | Nayyar | International Journal of Engineering & Technology. (n.d.). Retrieved April 19,
2022, from https://www.sciencepubco.com/index.php/ijet/article/view/11855
Azuma, R. , Baillot, Y. , Behringer, R. , Feiner, S. , Julier, S. , & MacIntyre, B. (2001). Recent
advances in augmented reality. IEEE Computer Graphics and Applications, 21(6), 34–47.
https://doi.org/10.1109/38.963459
Akçayır, M. , & Akçayır, G. (2017). Advantages and challenges associated with augmented
reality for education: A systematic review of the literature. Educational Research Review, 20,
1–11. https://doi.org/10.1016/J.EDUREV.2016.11.002

Digital Assistant in the Pharmaceutical Field for Advancing Healthcare

Systems
Keplar, K. E. , Urbanski, C. J. , and Kania, D. S. (2005) Update on personal digital assistant
applications for the healthcare provider. Ann. Pharmacother. 39(5), 892–907.
Lindquist, A. , Johansson, P. , Petersson, G. , Saveman, B. I. , and Nilsson, G. (2008) The use
of the Personal Digital Assistant (PDA) among personnel and students in health care: A review.
J. Med. Internet Res. 10(4), 1–15.
Lee, D. , and Yoon, S. N. (2021) Application of artificial intelligencebased technologies in the
healthcare industry: Opportunities and challenges. Int. J. Environ. Res. Public Health 18(1),
1–18.
https://www.prnewswire.com/in/news-releases/allianz-partnersexpands-its-digital-health-
assistant-to-ten-markets-in-asia-pacific805482211.html
Pastorino, R. , De Vito, C. , Migliara, G. , Glocker, K. , Binenbaum, I. , Ricciardi, W. , and
Boccia, S. (2019) Benefits and challenges of Big Data in healthcare: an overview of the
European initiatives. Eur. J. Public Health 29(3), 23–27.
Hermon, R. , and Williams, P. A. (2014) Big data in healthcare: What is it used for? 40–49.
Bohr, A. , and Memarzadeh, K. (2020) The rise of artificial intelligence in healthcare
applications. In Artificial Intelligence in healthcare (pp. 25–60). Academic Press.
Singhal, S. , and Carlton, S. (2019) The era of exponential improvement in healthcare.
McKinsey & Company 1–16.
Khezr, S. , Moniruzzaman, M. , Yassine, A. , and Benlamri, R. (2019) Blockchain technology in
healthcare: A comprehensive review and directions for future research. Appl. Sci. 9(9), 1–28.
Haleem, A. , Javaid, M. , Singh, R. P. , Suman, R. , and Rab, S. (2021) Blockchain technology
applications in healthcare: An overview. International Journal of Intelligent Networks 2,
130–139.
Liang, X. , Zhao, J. , Shetty, S. , Liu, J. , and Li, D. (2017) Integrating blockchain for data
sharing and collaboration in mobile healthcare applications. In 2017 IEEE 28th annual
international symposium on personal, indoor, and mobile radiocommunications (PIMRC) (pp.
1–5). IEEE.
Javaid, M. , and Khan, I. H. (2021) Internet of Things (IoT) enabled healthcare helps to take the
challenges of COVID-19 Pandemic. J. Oral Biol. Craniofac. Res. 11(2), 209–214.
Kelly, J. T. , Campbell, K. L. , Gong, E. , and Scuffham, P. (2020) The Internet of Things: Impact
and implications for health care delivery. J. Med. Internet Res. 22(11), 1–11.
Weinstein, R. S. , Lopez, A. M. , Joseph, B. A. , Erps, K. A. , Holcomb, M. , Barker, G. P. , and
Krupinski, E. A. (2014) Telemedicine, telehealth, and mobile health applications that work:
opportunities and barriers. Am. J. Med. 127(3), 183–187.
Haleem, A. , Javaid, M. , Singh, R. P. , and Suman, R. (2021) Telemedicine for healthcare:
Capabilities, features, barriers, and applications. Sensors International, 2, 1–12.
Weightman, M. (2020) Digital psychotherapy as an effective and timely treatment option for
depression and anxiety disorders: Implications for rural and remote practice. J. Int. Med. Res.
48(6), 1–7.
Batterham, P. J. , Sunderland, M. , Calear, A. L. , Davey, C. G. , Christensen, H. , Teesson, M. ,
Kay-Lambkin, F. , Andrews, G. , Mitchell, P. B. , Herrman, H. , and Butow, P. N. (2015)
Developing a roadmap for the translation of e-mental health services for depression. Aust. N. Z.
J. Psychiatry, 49(9), 776–784.
You, Y. , and Gui, X. (2020) Self-Diagnosis through AI-enabled Chatbotbased Symptom
Checkers: User Experiences and Design Considerations. AMIA Annu. Symp. Proc. 2020,
1354–1363.
Faris, H. , Habib, M. , Faris, M. , Elayan, H. , and Alomari, A. (2021) An intelligent multimodal
medical diagnosis system based on patients’ medical questions and structured symptoms for
telemedicine. Inform. Med. Unlocked, 23, 1–12.
https://developer.infermedica.com/docs/introductionv
Burke, L. E. , Conroy, M. B. , Sereika, S. M. , Elci, O. U. , Styn, M. A. , Acharya, S. D. , Sevick,
M. A. , Ewing, L. J. , and Glanz, K. (2011) The effect of electronic self-monitoring on weight loss
and dietary intake: a randomized behavioral weight loss trial. Obesity 19(2), 338–344.
Sevick, M. A. , Zickmund, S. , Korytkowski, M. , Piraino, B. , Sereika, S. , Mihalko, S. ,
Snetselaar, L. , Stumbo, P. , Hausmann, L. , Ren, D. , and Marsh, R. (2008) Design, feasibility,
and acceptability of an intervention using personal digital assistant-based self-monitoring in
managing type 2 diabetes. Contemp. Clin. Trials, 29(3), 396–409.
Acharya, S. D. , Elci, O. U. , Sereika, S. M. , Styn, M. A. , and Burke, L. E. (2011) Using a
personal digital assistant for self-monitoring influences diet quality in comparison to a standard
paper record among overweight/obese adults. J. Am. Diet. Assoc. 111(4), 583–588.
Ambinder, E. P. (2005) Electronic health records. J. Oncol. Pract. 1(2), 57–63.
https://www.healthit.gov/faq/what-electronic-health-record-her
Bajpai, N. , and Wadhwa, M. (2020) India’s National Digital Health Mission. 1–28.
Tang, P. C. , and McDonald, C. J. (2006) Electronic health record systems. In Biomedical
informatics (pp. 447–475). Springer, New York, NY.
Pryor, T. (1983) Gardner RM. Clayton PD and Warner HR: The HELP system. J. 87-102.
Octo Barnett, G. (1989) The application of computer-based medicalrecord systems in
ambulatory practice. In Implementing Health Care Information Systems, 85–99.
Ozair, F. F. , Jamshed, N. , Sharma, A. , and Aggarwal, P. (2015) Ethical issues in electronic
health records: A general overview. Perspect. Clin. Res. 6(2), 73–76.
Vance, B. , Tomblin, B. , Studney, J. , and Coustasse, A. (2015) Benefits and barriers for
adoption of personal health records. Business and Health Administration Association Annual
Conference, at the 51st Annual Midwest Business Administration Association International
Conference, Chicago, IL, 1–16.
Sharp, L. K. , Carvalho, P. , Southward, M. , Schmidt, M. L. , Jabine, L. N. , Stolley, M. R. , and
Gerber, B. S. (2014) Electronic personal health records for childhood cancer survivors: an
exploratory study. J. Adolesc. Young Adult Oncol. 3(3), 117–122.
Scherger, J. E. (2005) Primary care needs a new model of office practice. BMJ, 330(7504),
358–E359.
Fuji, K. T. , Abbott, A. A. , Galt, K. A. , Drincic, A. , Kraft, M. , and Kasha, T. (2012) Standalone
personal health records in the United States: meeting patient desires. Health Technol. 2(3),
197–205.
Gubbi, J. , Buyya, R. , Marusic, S. , and Palaniswami, M. (2013) Internet of Things (IoT): A
vision, architectural elements, and future directions. Future Gener. Comput. Syst. 29(7),
1645–1660.
Li, S. , Da Xu, L. , and Zhao, S. (2018) 5G Internet of Things: A survey. J. Ind. Inf. Integr. 10,
1–9.
https://www.mayoclinic.org/healthy-lifestyle/consumer-health/in-depth/personal-health-
record/art-20047273
https://www.limswiki.org/index.php/Medical_practice_management_system
Davey, S. , and Davey, A. (2015) Effect of practice management softwares among physicians of
developing countries with special reference to Indian scenario by Mixed Method Technique. J.
Family Med. Prim. Care 4(2), 208–216.
http://www.binaryspectrum.com/industries/healthcare/focusareas/practice_management_softwa
re-val.html
Ta, V. D. , Liu, C. M. , and Nkabinde, G. W. (2016, July) Big data stream computing in
healthcare real-time analytics. In 2016 IEEE international conference on cloud computing and
big data analysis (ICCCBDA) (pp. 37–42). IEEE.
Marx, V. (2013) The big challenges of big data. Nature 498(7453), 255260.
Vayena, E. , and Gasser, U. (2016) Strictly biomedical? Sketching the ethics of the big data
ecosystem in biomedicine. In The ethics of biomedical big data (pp. 17–39). Springer, Cham.
Ienca, M. , Vayena, E. , and Blasimme, A. (2018) Big data and dementia: charting the route
ahead for research, ethics, and policy. Front. Med. 5, 1–7.
Luo, J. , Wu, M. , Gopukumar, D. , and Zhao, Y. (2016) Big data application in biomedical
research and health care: a literature review. Biomed. Inform. Insights 8, 1–10.
Schuster, S. C. (2008) Next-generation sequencing transforms today’s biology. Nat. Methods,
5(1), 16–18.
Morozova, O. , and Marra, M. A. (2008) Applications of next-generation sequencing
technologies in functional genomics. Genomics 92(5), 255264.
Taylor, R. C. . (2010) An overview of the Hadoop/MapReduce/HBase framework and its current
applications in bioinformatics. BMC Bioinform. 11(12), 1–6.
Reis, B. Y. , Kohane, I. S. , and Mandl, K. D. (2009) Longitudinal histories as predictors of future
diagnoses of domestic abuse: modelling study. Bmj. 339. 849.
Murdoch, T. B. , and Detsky, A. S. (2013) The inevitable application of big data to health care.
Jama 309(13), 1351–1352.
Rallapalli, S. , Gondkar, R. , and Ketavarapu, U. P. K. (2016) Impact of processing and
analyzing healthcare big data on cloud computing environment by implementing hadoop cluster.
Procedia Comput. Sci. 85, 16–22.
Beakta, R. (2015) Big data and hadoop: A review paper. Int. J. Comput. Sci. Inf. Technol. 2(2),
13–15.
Augustine, D. P. (2014) Leveraging big data analytics and Hadoop in developing India’s
healthcare services. Int. J. Comput. Appl. 89(16), 4450.
Sharma, S. , Chen, K. , and Sheth, A. (2018) Toward practical privacypreserving analytics for
IoT and cloud-based healthcare systems. IEEE Internet Comput. 22(2), 42–51.
Dalal, P. , Aggarwal, G. , and Tejasvee, S. (2020, April) Internet of Things (IoT) in Healthcare
System: IA3 (Idea, Architecture, Advantages and Applications). In Proceedings of the
International Conference on Innovative Computing & Communications (ICICC), 1–6.
Ibrahim, A. U. , Al-Turjman, F. , Sa'id, Z. , and Ozsoz, M. (2020) Futuristic CRISPR-based
biosensing in the cloud and internet of things era: an overview. Multimed. Tools Appl. 1–29.
Duan, R. , Chen, X. , and Xing, T. (2011, October) A QoS architecture for IOT. In 2011
International Conference on Internet of Things and 4th International Conference on Cyber,
Physical and Social Computing (pp. 717–720). IEEE.
Khattak, H. A. , Shah, M. A. , Khan, S. , Ali, I. , and Imran, M. (2019) Perception layer security in
Internet of Things. Future Gener. Comput. Syst. 100, 144–164.
Yang, Z. , Yue, Y. , Yang, Y. , Peng, Y. , Wang, X. and Liu, W. (2011, July) Study and
application on the architecture and key technologies for IOT. In 2011 International Conference
on Multimedia Technology (pp. 747–751). IEEE.
Urien, P. , Elrharbi, S. , Nyamy, D. , Chabanne, H. , Icart, T. , Lecocq, F. , Pépin, C. , Toumi, K.
, Bouet, M. , Pujolle, G. and Krzanik, P. (2009, November) HIP-Tags architecture
implementation for the Internet of Things. In 2009 First Asian Himalayas International
Conference on Internet (pp. 1–5). IEEE.
Sun, X. , and Ansari, N. (2017) Traffic load balancing among brokers at the IoT application
layer. IEEE Trans. Netw. Serv. Manag. 15(1), 489502.
Zhong, C. L. , Zhu, Z. and Huang, R. G. (2015, August) Study on the IOT architecture and
gateway technology. In 2015 14th International Symposium on Distributed Computing and
Applications for Business Engineering and Science (DCABES) (pp. 196–199). IEEE.
Rong, G. , Mendez, A. , Assi, E. B. , Zhao, B. , and Sawan, M. (2020) Artificial intelligence in
healthcare: review and prediction case studies. Engineering 6(3), 291–301.
Hudec, M. , and Smutny, Z. (2017) RUDO: A home ambient intelligence system for blind
people. Sensors 17(8), 1–45.
Man, D. W. K. , Tam, S. F. , and Hui-Chan, C. W. Y. (2003) Learning to live independently with
expert systems in memory rehabilitation. NeuroRehabilitation 18(1), 21–29.
Wei, Y. , Zhou, J. , Wang, Y. , Liu, Y. , Liu, Q. , Luo, J. , Wang, C. , Ren, F. , and Huang, L.
(2020) A review of algorithm & hardware design for AI-based biomedical applications. IEEE
transactions on biomedical circuits and systems, 14(2), pp.145-163.
Shukla, S. , Lakhmani, A. , and Agarwal, A. K. (2016, April) Approaches of artificial intelligence
in biomedical image processing: A leading tool between computer vision & biological vision. In
2016 International Conference on Advances in Computing, Communication, & Automation
(ICACCA)(Spring) (pp. 1–6). IEEE.
Blasimme, A. , and Vayena, E. (2019) The ethics of AI in biomedical research, patient care and
public health. Patient Care and Public Health (April 9, 2019). In Oxford Handbook of Ethics of
Artificial Intelligence, Forthcoming, 703–718.
Davenport, T. , and Kalakota, R. (2019) The potential for artificial intelligence in healthcare.
Future Healthcare Journal 6(2), 94–98.
Park, S. H. , and Han, K. (2018) Methodologic guide for evaluating clinical performance and
effect of artificial intelligence technology for medical diagnosis and prediction. Radiology 286(3),
800–809.
Yu, C. , and Helwig, E. J. (2021) The role of AI technology in prediction, diagnosis and
treatment of colorectal cancer. Artif. Intell. Rev. 55, 323–343.
Yu, J. , Park, S. , Kwon, S. H. , Ho, C. M. B. , Pyo, C. S. , and Lee, H. (2020) AI-based stroke
disease prediction system using real-time electromyography signals. Appl. Sci. 10, 1–19.
Krittanawong, C. , Zhang, H. , Wang, Z. , Aydar, M. , and Kitai, T. (2017) Artificial intelligence in
precision cardiovascular medicine. J. Am. Coll. Cardiol. 69(21), 2657–2664.
Wood, G. (2014) Ethereum: A secure decentralised generalised transaction ledger. Ethereum
Project Yellow Paper 151(2014), 1–32.
Fekih, R. B. , and Lahami, M. (2020, June) Application of blockchain technology in healthcare: A
comprehensive study. In International Conference on Smart Homes and Health Telematics (pp.
268–276). Springer, Cham.
Siyal, A. A. , Junejo, A. Z. , Zawish, M. , Ahmed, K. , Khalil, A. , and Soursou, G. (2019)
Applications of blockchain technology in medicine and healthcare: Challenges and future
perspectives. Cryptography 3(1), 1–16.
Hathaliya, J. , Sharma, P. , Tanwar, S. , and Gupta, R . (2019, December) Blockchain-based
remote patient monitoring in healthcare 4.0. In 2019 IEEE 9th International Conference on
Advanced Computing (IACC) (pp. 87–91). IEEE.
Gupta, R. , Tanwar, S. , Kumar, N. , and Tyagi, S. (2020) Blockchainbased security attack
resilience schemes for autonomous vehicles in industry 4.0: A systematic review. Comput.
Electr. Eng. 86, 1–15.
Griggs, K. N. , Ossipova, O. , Kohlios, C. P. , Baccarini, A. N. , Howson, E. A. , and Hayajneh,
T. (2018) Healthcare blockchain system using smart contracts for secure automated remote
patient monitoring. J. Med. Syst. 42(7), 1–7.
Uddin, M. A. , Stranieri, A. , Gondal, I. , and Balasubramanian, V. (2019, October.) A
decentralized patient agent controlled blockchain for remote patient monitoring. In 2019
International Conference on Wireless and Mobile Computing, Networking and Communications
(WiMob) (pp. 18). IEEE.
Bocek, T. , Rodrigues, B. B. , Strasser, T. , and Stiller, B. (2017, May) Blockchains everywhere-
a use-case of blockchains in the pharma supply-chain. In 2017 IFIP/IEEE symposium on
integrated network and service management (IM) (pp. 772–777). IEEE.
Sylim, P. , Liu, F. , Marcelo, A. , and Fontelo, P. (2018) Blockchain technology for detecting
falsified and substandard drugs in distribution: pharmaceutical supply chain intervention. Jmir
Res. Protoc. 7(9), 1–13.
Haq, I. , and Esuka, O. M. (2018) Blockchain technology in pharmaceutical industry to prevent
counterfeit drugs. Int. J. Comput. Appl. 180(25), 8–12.
Jamil, F. , Hang, L. , Kim, K. , and Kim, D. (2019) A novel medical blockchain model for drug
supply chain integrity management in a smart hospital. Electronics 8(5), 1–32.
Xu, X. , Weber, I. , Staples, M. , Zhu, L. , Bosch, J. , Bass, L. , Pautasso, C. , and Rimba, P.
(2017, April) A taxonomy of blockchain-based systems for architecture design. In 2017 IEEE
international conference on software architecture (ICSA) (pp. 243–252). IEEE.
He, X. , Alqahtani, S. , and Gamble, R. (2018, July) Toward privacyassured health insurance
claims. In 2018 IEEE International Conference on Internet of Things (iThings) and IEEE Green
Computing and Communications (GreenCom) and IEEE Cyber, Physical and Social Computing
(CPSCom) and IEEE Smart Data (SmartData) (pp. 1634–1641). IEEE.
Thenmozhi, M. , Dhanalakshmi, R. , Geetha, S. and Valli, R. (2021) Implementing blockchain
technologies for health insurance claim processing in hospitals. Mater. Today: Proc. 1–4.
Saldamli, G. , Reddy, V. , Bojja, K. S. , Gururaja, M. K. , Doddaveerappa, Y. , and Tawalbeh, L.
(2020, April) Health care insurance fraud detection using blockchain. In 2020 Seventh
International Conference on Software Defined Systems (SDS) (pp. 145–152). IEEE.
Dasgupta, A. , and Deb, S. (2008) Telemedicine: A new horizon in public health in India. Indian
J. Community Med. 33(1), 3–8.
Hjelm, N. M. (2005) Benefits and drawbacks of telemedicine. J. Telemed. Telecare 11(2),
60–70.
Zhang, Y. , Bai, J. , Zhou, X. , Dai, B. , Cui, Z. , Lin, J. , Ding, C. , Zhang, P. , Yu, B. , Ye, L. ,
and Shen, D. (1997) First trial of home ECG and blood pressure telemonitoring system in
Macau. Telemed. J. 3(1), 67–72.
Craig, J. , and Petterson, V. (2005) Introduction to the practice of telemedicine. J. Telemed.
Telecare 11(1), 3–9.

Deep Learning Techniques and Drug Release

Yusuf, A. , Sebastien, B. , Samira, E. , Charlie, G. , Brendan, L. , Eric, M. , Cosmic, P. , and
Alfredo, S. (2016). Deep Learning. Chapter 1, Introduction.
Xu, Y. , Dai, Z. , Chen, F. , Gao, S. , Pei, J. , and Lai, L. (2015) Deep learning for drug-induced
liver injury. J. Chem. Inf. Model.. 55, 2085–2093.
Bengio, Y. , Courville, A. , and Vincent, P. (2013) Representation learning: a review and new
perspectives. IEEE Transactions on Pattern Analysis and Machine Intelligence. 35, 1798–1828.
LeCun, Y. , Bengio, Y. , and Hinton, G. (2015) Deep learning. Nature. 521, 436–444.
Schmidhuber, J. (2015). Deep learning in neural networks: an overview. Neural. Netw. 61,
85–117.
Krizhevsky, A. , Sutskever, I. , and Hinton, G.E. (2012) Imagenet classification with deep
convolutional neural networks. Advances in Neural Information Processing Systems. 25.
Hinton, G. , Deng, L. , Yu, D. , Dahl, G.E. , Mohamed, A.R. , Jaitly, N. , Senior, A. , Vanhoucke,
V. , Nguyen, P. , Sainath, T.N. , and Kingsbury, B. (2012) Deep neural networks for acoustic
modeling in speech recognition: the shared views of four research groups. IEEE Signal
Processing Magazine. 29, 82–97.
Jin, S. , Zeng, X. , Xia, F. , Huang, W. , and Liu, X. (2021) Application of deep learning methods
in biological networks. Briefings in Bioinformatics. 22, 1902–1917.
Winnicka, K. (2021). Advanced materials in drug release and drug delivery systems. Materials.
14, 1042.
Kalaiselvi, T. , & Padmapriya, S. T. (2021). Brain tumor diagnostic system—a deep learning
application. Machine Vision Inspection Systems, Volume 2: Machine Learning-Based
Approaches, 69–90.
Lusci, A. , Pollastri, G. , and Baldi, Pierre . (2013) Deep architectures and deep learning in
chemoinformatics: the prediction of aqueous solubility for drug-like molecules. J. Chem. Inform.
Model.. 53, 1563–1575.
Mamoshina, P. , Vieira, A. , Putin, E. , and Zhavoronkov, A. (2016) Applications of deep
learning in biomedicine. Mol. Pharm. 13, 1445–1454.
Xu, Y. , Zhou, Y. , Sekula, P. , and Ding, L. (2021) Machine learning in construction: from
shallow to deep learning. Dev. Built. Environ. 6, 100045.
Kim, I.-W. , Oh, J.M. (2017) Deep learning: from chemoinformatics to precision medicine. J.
Pharm. Invest. 47, 317–323.
Schmidhuber, J. (2015). Deep learning in neural networks: an overview. Neura.l Netw. 61,
85–117.
Zawbaa, H.M. , Szlęk, J. , Grosan, C. , Jachowicz, R. , and Mendyk, A. (2016) Computational
intelligence modeling of the macromolecules release from PLGA microspheres—focus on
feature selection. PLoS. One. 11, e0157610.
Scannell, J.W. , Blanckley, A. , Boldon, H. , and Warrington, B. (2012) Diagnosing the decline in
pharmaceutical R&D efficiency. Nat. Rev. Drug. Discov. 11, 191–200.
Lee, P. I. , & Li, J. X. (2010). Evolution of oral controlled release dosage forms. Oral controlled
release formulation design and drug delivery. John Wiley & Sons, Inc, 21–31.
Park, K. (2015) Drug delivery of the future: chasing the invisible gorilla. J. Control. Release.
240, 2–8.
Park, K. (2014) Controlled drug delivery systems: Past forward and future back. J. Control.
Release. 190, 3–8
Yang, Y. , Ye, Z. , Su, Y. , Zhao, Q. , Li, X. , and Ouyang, D. (2019). Deep learning for in vitro
prediction of pharmaceutical formulations. Acta pharmaceutica sinica B, 9(1), 177–185.
Xu, Y. , Dai, Z. , Chen, F. , Gao, S. , Pei, J. , and Lai, L. (2015). Deep learning for drug-induced
liver injury. Journal of chemical information and modeling, 55(10), 2085–2093.
Ramsundar, B. , Liu, B. , Wu, Z. , Verras, A. , Tudor, M. , Sheridan, R. P. , & Pande, V. (2017).
Is multitask deep learning practical for pharma?. Journal of chemical information and modeling,
57(8), 2068–2076.
Altae-Tran, H. , Ramsundar, B. , Pappu, A. S. , & Pande, V. (2017). Low data drug discovery
with one-shot learning. ACS central science, 3(4), 283–293.
Hosny, A. , Parmar, C. , Quackenbush, J. , Schwartz, L. H. , & Aerts, H. J. (2018). Artificial
intelligence in radiology. Nature Reviews Cancer, 18(8), 500–510.
Wu, N. , Phang, J. , Park, J. , Shen, Y. , Huang, Z. , Zorin, M. , & Geras, K. J. (2019). Deep
neural networks improve radiologists’ performance in breast cancer screening. IEEE
transactions on medical imaging, 39(4), 1184–1194.
McKinney, S. M. , Sieniek, M. , Godbole, V. , Godwin, J. , Antropova, N. , Ashrafian, H. , &
Shetty, S. (2020). International evaluation of an AI system for breast cancer screening. Nature,
577(7788), 89–94.
Zhavoronkov, A. , Ivanenkov, Y. A. , Aliper, A. , Veselov, M. S. , Aladinskiy, V. A. , Aladinskaya,
A. V. , ... & Aspuru-Guzik, A. (2019). Deep learning enables rapid identification of potent DDR1
kinase inhibitors. Nature biotechnology, 37(9), 1038–1040.
Stokes, J. M. , Yang, K. , Swanson, K. , Jin, W. , Cubillos-Ruiz, A. , Donghia, N. M. , & Collins,
J. J. (2020). A deep learning approach to antibiotic discovery. Cell, 180(4), 688–702.
Langner, S. , Häse, F. , Perea, J. D. , Stubhan, T. , Hauch, J. , Roch, L. M. , & Brabec, C. J.
(2020). Beyond ternary OPV: high-throughput experimentation and self-driving laboratories
optimize multicomponent systems. Advanced Materials, 32(14), 1907801.
MacLeod, B. P. , Parlane, F. G. , Morrissey, T. D. , Häse, F. , Roch, L. M. , Dettelbach, K. E. , &
Berlinguette, C. P. (2020). Self-driving laboratory for accelerated discovery of thin-film materials.
Science Advances, 6(20), eaaz8867.
McCoubrey, L. E. , Elbadawi, M. , Orlu, M. , Gaisford, S. , & Basit, A. W. (2021). Harnessing
machine learning for development of microbiome therapeutics. Gut Microbes, 13(1), 1872323.
Rafi, T. H. (2021). A Brief Review on Spiking Neural Network-A Biological Inspiration.
McCoubrey, L. E. , Elbadawi, M. , Orlu, M. , Gaisford, S. , & Basit, A. W. (2021). Harnessing
machine learning for development of microbiome therapeutics. Gut Microbes, 13(1), 1872323.
Schmidt, B. , & Hildebrandt, A. (2021). Deep learning in next-generation sequencing. Drug
Discovery Today, 26(1), 173–180.
Das, S. C. , & Prakash, A. (2021). A Systematic Review on Drug Delivery Systems Based on
Their Mechanism of Drug Release and Their Applications. International Journal for Research in
Applied Sciences and Biotechnology, 8(3), 55–63.
Cohen, S. (2021). The basics of machine learning: strategies and techniques. In Artificial
Intelligence and Deep Learning in Pathology (pp. 13–40). Elsevier.
Vamathevan, J. , Clark, D. , Czodrowski, P. , Dunham, I. , Ferran, E. , Lee, G. , & Zhao, S.
(2019). Applications of machine learning in drug discovery and development. Nature reviews
Drug discovery, 18(6), 463–477.
Kumar, V. , & Dogra, N. (2021). A comprehensive review on deep synergistic drug prediction
techniques for cancer. Archives of Computational Methods in Engineering, 1–19.
Lavecchia, A. (2019). Deep learning in drug discovery: opportunities, challenges and future
prospects. Drug discovery today, 24(10), 20172032.
Ching, T. , Himmelstein, D. S. , Beaulieu-Jones, B. K. , Kalinin, A. A. , Do, B. T. , Way, G. P. , &
Greene, C. S. (2018). Opportunities and obstacles for deep learning in biology and medicine.
Journal of the Royal Society Interface, 15(141), 20170387.
Piroozmand, F. , Mohammadipanah, F. , & Sajedi, H. (2020). Spectrum of deep learning
algorithms in drug discovery. Chemical Biology & Drug Design, 96(3), 886–901.
Yin, C. , Zhu, Y. , Fei, J. , & He, X. (2017). A deep learning approach for intrusion detection
using recurrent neural networks. Ieee Access, 5, 21954–21961.
Ju, C. , Bibaut, A. , & van der Laan, M. (2018). The relative performance of ensemble methods
with deep convolutional neural networks for image classification. Journal of Applied Statistics,
45(15), 2800–2818.
Shetty, D. , Varma, J. , Navi, S. , & Ahmed, M. (2020). Diving deep into deep learning: history,
evolution, types and applications. The International Journal on Media Management, 9.
2278–3075. Shetty, D. , Varma, J. , Navi, S. , & Ahmed, M. (2020). Diving deep into deep
learning: history, evolution, types and applications. The International Journal on Media
Management, 9, 2278–3075.
Akay, A. , & Hess, H. (2019). Deep learning: current and emerging applications in medicine and
technology. IEEE journal of biomedical and health informatics, 23(3), 906–920.
Janiesch, C. , Zschech, P. , & Heinrich, K. (2021). Machine learning and deep learning.
Electronic Markets, 31(3), 685–695.
Kathiresan, K. , Pattanayek, S. , & Umamaheswari. (2020) E. Stimulus of artificial neural
network in drug discovery, development and research. International Journal of Pharmacy and
Industrial Research. 10(01):4550.
Sadeeq, M. A. , & Abdulazeez, A. M. (2020, December). Neural networks architectures design,
and applications: A review. In 2020 International Conference on Advanced Science and
Engineering (ICOASE) (pp. 199–204). IEEE.
Schmidhuber, J. (2015). Deep learning in neural networks: An overview. Neural networks, 61,
85–117.
Hock, S. C. , Siang, T. K. , & Wah, C. L. (2021). Continuous manufacturing versus batch
manufacturing: benefits, opportunities and challenges for manufacturers and regulators.
Generics and Biosimilars Initiative Journal, 10(1), 1–14.
Aliper, A. , Plis, S. , Artemov, A. , Ulloa, A. , Mamoshina, P. , & Zhavoronkov, A. (2016). Deep
learning applications for predicting pharmacological properties of drugs and drug repurposing
using transcriptomic data. Molecular pharmaceutics, 13(7), 2524–2530.
Ahmad, J. , Farman, H. , & Jan, Z. (2019). Deep learning methods and applications. In Deep
learning: convergence to big data analytics (pp. 31–42). Springer, Singapore.
Cao, Y. , Geddes, T. A. , Yang, J. Y. H. , & Yang, P. (2020). Ensemble deep learning in
bioinformatics. Nature Machine Intelligence, 2(9), 500–508.
Jing, Y. , Bian, Y. , Hu, Z. , Wang, L. , & Xie, X. Q. S. (2018). Deep learning for drug design: an
artificial intelligence paradigm for drug discovery in the big data era. The AAPS Journal, 20(3),
1–10.
Manco, L. , Maffei, N. , Strolin, S. , Vichi, S. , Bottazzi, L. , & Strigari, L. (2021). Basic of
machine learning and deep learning in imaging for medical physicists. Physica Medica, 83,
194–205.
Shone, N. , Ngoc, T. N. , Phai, V. D. , & Shi, Q. (2018). A deep learning approach to network
intrusion detection. IEEE transactions on emerging topics in computational intelligence, 2(1),
41–50.
Gómez-Bombarelli, R. , Wei, J. N. , Duvenaud, D. , Hernández-Lobato, J. M. , Sánchez-
Lengeling, B. , Sheberla, D. , & Aspuru-Guzik, A. (2018). Automatic chemical design using a
data-driven continuous representation of molecules. ACS central science, 4(2), 268–276.
Goodfellow, I. , Pouget-Abadie, J. , Mirza, M. , Xu, B. , Warde-Farley, D. , Ozair, S. , ... &
Bengio, Y. (2014). Generative adversarial nets. Advances in neural information processing
systems, 27.
Sanchez-Lengeling, B. , Outeiral, C. , Guimaraes, G. L. , & AspuruGuzik, A. (2017). Optimizing
distributions over molecular space. An objective-reinforced generative adversarial network for
inverse-design chemistry (ORGANIC).
Peng, X. , Wang, L. , Wang, X. , & Qiao, Y. (2016). Bag of visual words and fusion methods for
action recognition: Comprehensive study and good practice. Computer Vision and Image
Understanding, 150. 109125.
Liu, A. A. , Su, Y. T. , Jia, P. P. , Gao, Z. , Hao, T. , & Yang, Z. X. (2014). Multiple/single-view
human action recognition via part-induced multitask structural learning. IEEE transactions on
cybernetics, 45(6), 1194–1208.
Keerthana, V. , Mohaideen, S. S. , Vigneshwaran, L. V. , & Kumar, M. S. (2022). Role of
artificial intelligence in drug development. International Journal of Research in Pharmaceutical
Sciences and Technology, 3(1), Awaiting-Awaiting.
Baştanlar, Y. , & Özuysal, M. (2014). Introduction to machine learning. miRNomics: MicroRNA
biology and computational analysis. 105128.
Wani, M. A. , Bhat, F. A. , Afzal, S. , & Khan, A. I. (2020). Unsupervised deep learning
architectures. In Advances in Deep Learning (pp. 77–94). Springer, Singapore.
Ibric, S. , Djuriš, J. , Parojčić, J. , & Djurić, Z. (2012). Artificial neural net-works in evaluation and
optimization of modified release solid dosage forms. Pharmaceutics, 4(4), 531–550.
Shorten, C. , Khoshgoftaar, T. M. , & Furht, B. (2021). Deep learning applications for COVID-19.
Journal of Big Data, 8(1), 1–54.
Bengio, Y. , Simard, P. , & Frasconi, P. (1994). Learning long-term dependencies with gradient
descent is difficult. IEEE transactions on neural networks, 5(2), 157–166.
Saleem, M. , Valle, H. E. , Brown, S. , Winters, V. I. , & Mahmood, A. (2018). The hiperwall tiled-
display wall system for big-data research. Journal of Big Data, 5(1), 1–45.
Han, R. , Yang, Y. , Li, X. , & Ouyang, D. (2018). Predicting oral disintegrating tablet
formulations by neural network techniques. Asian journal of pharmaceutical sciences, 13(4),
336–342.
Ekins, S. (2016). The next era: deep learning in pharmaceutical research. Pharmaceutical
research, 33(11), 2594–2603.
Wang, W. , Ye, Z. , Gao, H. , & Ouyang, D. (2021). Computational pharmaceutics-A new
paradigm of drug delivery. Journal of Controlled Release, 338, 119–136.
Simões, M. F. , Silva, G. , Pinto, A. C. , Fonseca, M. , Silva, N. E. , Pinto, R. M. , & Simões, S.
(2020). Artificial neural networks applied to quality-by-design: From formulation development to
clinical outcome. European Journal of Pharmaceutics and Biopharmaceutics. 152, 282–295.
Waheed, A. , Kumar, A. , and Bindu, H. (2020). Assessing the role of artificial intelligence in the
design of drug delivery systems. International Journal of Medical Science and Diagnosis
Research (IJMSDR). 4(12):22-27.
Grassi, M. , & Grassi, G. (2014). Application of mathematical modeling in sustained release
delivery systems. Expert opinion on drug delivery, 11(8), 1299–1321.
Chen, G. , Li, J. , Zhang, S. , Song, C. , Li, G. , Sun, Z. , ... & You, J. (2012). A sensitive and
efficient method to systematically detect two biophenols in medicinal herb, herbal products and
rat plasma based on thorough study of derivatization and its convenient application to
pharmacokinetics with semi-automated device. Journal of Chromatography A, 1249, 190–200.
Hassanzadeh, P. , Atyabi, F. , & Dinarvand, R. (2019). The significance of artificial intelligence
in drug delivery system design. Advanced drug delivery reviews, 151, 169–190.
Nagy, B. , Petra, D. , Galata, D. L. , Démuth, B. , Borbás, E. , Marosi, G. , ... & Farkas, A.
(2019). Application of artificial neural networks for Process Analytical Technology-based
dissolution testing. International Journal of Pharmaceutics, 567. 118464.
Bannigan, P. , Aldeghi, M. , Bao, Z. , Häse, F. , Aspuru-Guzik, A. , & Allen, C. (2021). Machine
learning directed drug formulation development. Advanced Drug Delivery Reviews, 175.
113806.
Sethuraman, N. (2020). Artificial Intelligence: A New Paradigm for Pharmaceutical Applications
in Formulations Development. Indian Journal of Pharmaceutical Education and Research,
54(4), 843–846.
Manne, R. (2021). Machine learning techniques in drug discovery and development.
International Journal of Applied Research, 7(4), 21–28.
Yang, Y. , Ye, Z. , Su, Y. , Zhao, Q. , Li, X. , & Ouyang, D. (2019). Deep learning for in vitro
prediction of pharmaceutical formulations. Acta pharmaceutica sinica B, 9(1), 177–185.
Lusci, A. , Pollastri, G. , & Baldi, P. (2013). Deep architectures and deep learning in
chemoinformatics: the prediction of aqueous solubility for drug-like molecules. Journal of
chemical information and modeling, 53(7), 1563–1575.
Hughes, T. B. , Miller, G. P. , & Swamidass, S. J. (2015). Modeling epoxidation of drug-like
molecules with a deep machine learning network. ACS central science, 1(4), 168–180.
Xu, Y. , Dai, Z. , Chen, F. , Gao, S. , Pei, J. , & Lai, L. (2015). Deep learning for drug-induced
liver injury. Journal of chemical information and modeling, 55(10), 2085–2093.
Ma, J. , Sheridan, R. P. , Liaw, A. , Dahl, G. E. , & Svetnik, V. (2015). Deep neural nets as a
method for quantitative structure-activity relationships. Journal of chemical information and
modeling, 55(2), 263–274.
Vanhaelen, Q. , Mamoshina, P. , Aliper, A. M. , Artemov, A. , Lezhnina, K. , Ozerov, I. , ... &
Zhavoronkov, A. (2017). Design of efficient computational workflows for in silico drug
repurposing. Drug Discovery Today, 22(2), 210–222.
Wilson, W. I. , Peng, Y. , & Augsburger, L. L. (2005). Generalization of a prototype intelligent
hybrid system for hard gelatin capsule formulation development. AAPS PharmSciTech, 6(3),
E449-E457.
Aguilar-Díaz, J. E. , García-Montoya, E. , Suñe-Negre, J. M. , PérezLozano, P. , Miñarro, M. , &
Ticó, J. R. (2012). Predicting orally disintegrating tablets formulations of ibuprophen tablets: an
application of the new SeDeM-ODT expert system. European journal of pharmaceutics and
biopharmaceutics, 80(3), 638–648.
Aguilar, J. E. , Montoya, E. G. , Lozano, P. P. , Negre, J. M. S. , Carmona, M. M. , & Grau, J. R.
T. (2013). New SeDeM-ODT expert system: An expert system for formulation of orodispersible
tablets obtained by direct compression. In Formulation tools for pharmaceutical development
(pp. 137–154). Woodhead Publishing.
Zhang, Z. H. (2013). Expert system for the development and formulation of push–pull osmotic
pump tablets containing poorly water-soluble drugs. In Formulation tools for pharmaceutical
development (pp. 73108). Woodhead Publishing.
Zhang, Z. H. , Dong, H. Y. , Peng, B. , Liu, H. F. , Li, C. L. , & Liang, M. (2011). Design of an
expert system for the development and formulation of push–pull osmotic pump tablets
containing poorly water-soluble drugs. International journal of pharmaceutics, 410(1–2), 41–47.
Chalortham, N. , Ruangrajitpakorn, T. , Supnithi, T. , & Leesawat, P. (2013). Oxpirt: ontology-
based expert system for production of a generic immediate release tablet. In Formulation tools
for pharmaceutical development (pp. 203–228). Woodhead Publishing.
Mendyk, A. , Szle¸k, J. & Jachowicz, R., (2013). ME_expert 2.0: a heuristic decision support
system for microemulsions formulation development. In Formulation tools for pharmaceutical
development (pp. 39–71). Woodhead Publishing.
Trnka, H. , Wu, J. X. , Van De Weert, M. , Grohganz, H. , & Rantanen, J. (2013). Fuzzy logic-
based expert system for evaluating cake quality of freeze-dried formulations. Journal of
Pharmaceutical Sciences, 102(12), 4364–4374.
Merzlikine, A. , Abramov, Y. A. , Kowsz, S. J. , Thomas, V. H. , & Mano, T. (2011). Development
of machine learning models of β-cyclodextrin and sulfobutylether-β-cyclodextrin complexation
free energies. Internationanl journal of pharmaceutics, 418(2), 207–216.
Salma, H. , Melha, Y. M. , Sonia, L. , Hamza, H. , & Salim, N. (2021). Efficient prediction of in
vitro piroxicam release and diffusion from topical films based on biopolymers using deep
learning models and generative adversarial networks. Journal of pharmaceutical sciences,
110(6), 2531–2543.
Prescott, J. H. , Lipka, S. , Baldwin, S. , Sheppard, N. F. , Maloney, J. M. , Coppeta, J. , &
Santini, J. T. (2006). Chronic, programmed polypeptide delivery from an implanted,
multireservoir microchip device. Nature biotechnology, 24(4), 437–438.
Farra, R. , Sheppard Jr, N. F. , McCabe, L. , Neer, R. M. , Anderson, J. M. , Santini Jr, J. T. , &
Langer, R. (2012). First-in-human testing of a wirelessly controlled drug delivery microchip.
Science translational medicine, 4(122), 122ra21–122ra21.
De Matas, M. , Shao, Q. , Richardson, C. H. , & Chrystyn, H. (2008). Evaluation of in vitro in
vivo correlations for dry powder inhaler delivery using artificial neural networks. European
Journal of Pharmaceutical Sciences, 33(1), 80–90.
Brier, M. E. , Zurada, J. M. , & Aronoff, G. R. (1995). Neural network predicted peak and trough
gentamicin concentrations. Pharmaceutical research, 12(3), 406–412.
Veng-Pedersen, P. , & Modi, N. B. (1993). Application of neural networks to
pharmacodynamics. Journal of pharmaceutical sciences, 82(9), 918–926.
Gobburu, J. V. , & Shelver, W. H. (1995). Quantitative structure– pharmacokinetic relationships
(QSPR) of beta blockers derived using neural networks. Journal of pharmaceutical sciences,
84(7), 862–865.
Dowell, J. A. , Hussain, A. , Devane, J. , & Young, D. (1999). Artificial neural networks applied
to the in vitro—in vivo correlation of an extended-release formulation: Initial trials and
experience. Journal of pharmaceutical sciences, 88(1), 154–160.
Parojčić, J. , Ibrić, S. , Djurić, Z. , Jovanović, M. , & Corrigan, O. I. (2007). An investigation into
the usefulness of generalized regression neural network analysis in the development of level A
in vitro–in vivo correlation. European journal of pharmaceutical sciences, 30(3–4), 264–272.
Tan, C. , & Degim, I. T. (2012). Development of sustained release for-˙ mulation of an
antithrombotic drug and application of fuzzy logic. Pharmaceutical Development and
Technology, 17(2), 242–250.
Chen, Y. , McCall, T. W. , Baichwal, A. R. , & Meyer, M. C. (1999). The application of an
artificial neural network and pharmacokinetic simulations in the design of controlled-release
dosage forms. Journal of controlled release, 59(1), 33–41.
Aktas, E. , Eroglu, H. , Kockan, U. , & Oner, L. (2013). Systematic development of pH-
independent controlled release tablets of carvedilol using central composite design and artificial
neural networks. Drug development and industrial pharmacy, 39(8), 1207–1216.
Chansanroj, K. , Petrovic, J. , Ibrić, S. , & Betz, G. (2011). Drug release´ control and system
understanding of sucrose esters matrix tablets by artificial neural networks. European journal of
pharmaceutical sciences, 44(3), 321–331.
Peh, K. K. , Lim, C. P. , Quek, S. S. , & Khoh, K. H. (2000). Use of artificial neural networks to
predict drug dissolution profiles and evaluation of network performance using similarity factor.
Pharmaceutical research, 17(11), 1384–1389.
Asadi, H. , Rostamizadeh, K. , Salari, D. , & Hamidi, M. (2011). Preparation of biodegradable
nanoparticles of tri-block PLA–PEG–PLA copolymer and determination of factors controlling the
particle size using artificial neural network. Journal of microencapsulation, 28(5), 406–416.
Lim, C. P. , San Quek, S. , & Peh, K. K. (2003). Prediction of drug release profiles using an
intelligent learning system: an experimental study in transdermal iontophoresis. Journal of
pharmaceutical and biomedical analysis, 31(1), 159–168.
Mendyk, A. , Jachowicz, R. , & Dorożyński, P. (2006). Artificial neural networks in the modelling
of drugs release profiles from hydrodynamically balanced system. Acta Poloniae
Pharmaceutica. Drug Research, 63(1).
Belic, A. , Grabnar, I. , Karba, R. , & Mrhar, A. (2003). Pathwaysˇ of paracetamol absorption
from layered excipient suppositories: artificial intelligence approach. European journal of drug
metabolism and pharmacokinetics, 28(1), 31–40.
Petrovic, J. , Ibríc, S. , Betz, G. , Parojícić, J. , & Ðurić, Z. (2009). Appli-´ cation of dynamic
neural networks in the modeling of drug release from polyethylene oxide matrix tablets.
European journal of pharmaceutical sciences, 38(2), 172–180.
Maltarollo, V. G. , Gertrudes, J. C. , Oliveira, P. R. , & Honorio, K. M. (2015). Applying machine
learning techniques for ADME-Tox prediction: a review. Expert opinion on drug metabolism &
toxicology, 11(2), 259–271.
Lefnaoui, S. , Rebouh, S. , Bouhedda, M. , & Yahoum, M. M. (2020). Artificial neural network for
modeling formulation and drug permeation of topical patches containing diclofenac sodium.
Drug Delivery and Translational Research, 10(1), 168–184.
Lefnaoui, S. , Rebouh, S. , Bouhedda, M. , Yahoum, M. M. , & Hanini, S. (2018). Artificial neural
network modeling of sustained antihypertensive drug delivery using polyelectrolyte complex
based on carboxymethyl-kappa-carrageenan and chitosan as prospective carriers. In 2018
International conference on applied smart systems (ICASS) (pp. 1–8). IEEE.
Simon, L. , & Fernandes, M. (2004). Neural network-based prediction and optimization of
estradiol release from ethylene–vinyl acetate membranes. Computers & chemical engineering,
28(11), 2407–2419.

Tissue Response Study using Deep Learning Techniques

Galon, J. , et al. (2006). Type, density, and location of immune cells within human colorectal
tumors predict clinical outcome. Science, 313(5795), 1960–1964.
Torre, L. A. et al. (2015). Global cancer statistics, 2012. CA: a cancer journal for clinicians,
65(2), 87–108.
Ettinger, D. S. et al. (2012). Non–Small Cell Lung Cancer. Journal of the National
Comprehensive Cancer Network, 10(10), 1236–1271.
Goldstraw, P et al. (2016). The IASLC Lung Cancer Staging Project: Proposals for Revision of
the TNM Stage Groupings in the Forthcoming (Eighth) Edition of the TNM Classification for
Lung Cancer. Journal of Thoracic Oncology, 11(1), 39–51.
Eisenhauer E. A. et al. (2009). New response evaluation criteria in solid tumours: Revised
RECIST guideline (version 1.1)., 45(2), 0–247.
Hosny, A. et al. (2018). Artificial intelligence in radiology. Nature Reviews Cancer, 18(8),
500–510.
Parmar C. et al. (2015). Machine learning methods for quantitative radiomic biomarkers.
Scientific reports, 5(1), 1–11.
Hosny, A. et al. (2018). Artificial intelligence in radiology. Nature Reviews Cancer, 18(8),
500–510.
Parmar, C. et al. (2015). Machine learning methods for quantitative radiomic biomarkers.
Scientific reports, 5(1), 1–11.
Aerts, H. J. (2018). Data science in radiology: a path forward. Clinical Cancer Research, 24(3),
532–534.
Aerts, H.J. et al . (2014). Decoding tumour phenotype by noninvasive imaging using a
quantitative radiomics approach. Nature communications, 5(1), 1–9.
Hosny, A. et al. (2018). Deep learning for lung cancer prognostication: a retrospective multi-
cohort radiomics study. PLoS medicine, 15(11), e1002711.
Parmar, C. et al. (2018). Data analysis strategies in medical imaging. Clinical cancer research,
24(15), 3492–3499.
Coroller, T. P. et al. (2017). Radiomic-based pathological response prediction from primary
tumors and lymph nodes in NSCLC. Journal of Thoracic Oncology, 12(3), 467–476.
Huynh, E. et al. (2016). CT-based radiomic analysis of stereotactic body radiation therapy
patients with lung cancer. Radiotherapy and Oncology, 120(2), 258–266.
Coroller, T. P. et al. (2016). Radiomic phenotype features predict pathological response in non-
small cell lung cancer. Radiotherapy and oncology, 119(3), 480–486.
Coroller, T. P. et al. (2015). CT-based radiomic signature predicts distant metastasis in lung
adenocarcinoma. Radiotherapy and Oncology, 114(3), 345–350.
LeCun, Y. et al. (2015). Deep learning. nature, 521(7553), 436–444.
Dandıl, E. et al. (2014, August). Artificial neural network-based classification system for lung
nodules on computed tomography scans. In 2014 6th International conference of soft computing
and pattern recognition (SoCPaR) (pp. 382–386). Ieee.
Shin, H. C. et al. (2016). Deep convolutional neural networks for computer-aided detection:
CNN architectures, dataset characteristics and transfer learning. IEEE transactions on medical
imaging, 35(5), 1285–1298.
Jamal-Hanjani, M. et al. (2017). Tracking the evolution of non–smallcell lung cancer. New
England Journal of Medicine, 376(22), 21092121.
Hermann, P. C. et al. (2007). Distinct populations of cancer stem cells determine tumor growth
and metastatic activity in human pancreatic cancer. Cell stem cell, 1(3), 313–323.
Donahue, J. et al. (2015). Long-term recurrent convolutional networks for visual recognition and
description. In Proceedings of the IEEE conference on computer vision and pattern recognition
(pp. 2625–2634).
Smith, S. M. , et al. (2004). Advances in functional and structural MR image analysis and
implementation as FSL. Neuroimage, 23, S208s219.
Litjens, G. et al. (2017). A survey on deep learning in medical image analysis. Medical image
analysis, 42, 60–88.
Shen, D. et al. (2017). Deep learning in medical image analysis. Annual review of biomedical
engineering, 19, 221–248.
Parvin, B. et al. (2007). Iterative voting for inference of structural saliency and characterization
of subcellular events. IEEE Transactions on Image Processing, 16(3), 615–623.
Parvin, B. et al. (2007). Iterative voting for inference of structural saliency and characterization
of subcellular events. IEEE Transactions on Image Processing, 16(3), 615–623.
Arteta, C. et al. (2012, October). Learning to detect cells using nonoverlapping extremal
regions. In International conference on medical image computing and computer-assisted
intervention (pp. 348–356). Springer, Berlin, Heidelberg.
Mualla, F. et al. (2013). Automatic cell detection in bright-field microscope images using SIFT,
random forests, and hierarchical clustering. IEEE transactions on medical imaging, 32(12),
2274–2286.
Niazi, M. K. K. , et al. (2013, March). An automated method for counting cytotoxic T-cells from
CD8 stained images of renal biopsies. In Medical Imaging 2013: Digital Pathology (Vol. 8676,
pp. 60–69). SPIE.
LeCun, Y. , et al. (1998). Gradient-based learning applied to document recognition. Proceedings
of the IEEE, 86(11), 2278–2324.
Ciresşan, D. C. , et al. (2013). Mitosis detection in breast cancer histology images with deep
neural networks. In International conference on medical image computing and computer-
assisted intervention (pp. 411–418). Springer, Berlin, Heidelberg.
Ruifrok, A. C. , & Johnston, D. A. (2001). Quantification of histochemical staining by colour
deconvolution. Analytical and quantitative cytology and histology, 23(4), 291–299.
Keshava, N. (2003). A survey of spectral unmixing algorithms. Lincoln laboratory journal, 14(1),
55–78.
Fedorov, A. , et al. (2012). 3D Slicer as an image computing platform for the Quantitative
Imaging Network. Magnetic resonance imaging, 30(9), 1323–1341.
Krizhevsky, A. , et al. (2012). Imagenet classification with deep convolutional neural networks.
Advances in neural information processing systems, 25.
Rubins, J. , et al. (2007). Follow-up and surveillance of the lung cancer patient following curative
intent therapy: ACCP evidence-based clinical practice guideline. Chest, 132(3), 355S–367S.
Calman, L. , et al. (2011). Survival benefits from follow-up of patients with lung cancer: a
systematic review and meta-analysis. Journal of Thoracic Oncology, 6(12), 1993–2004.
Ioffe, S. , & Szegedy, C. (2015, June). Batch normalization: Accelerating deep network training
by reducing internal covariate shift. In International conference on machine learning (pp.
448–456). PMLR.
Srivastava, N. , et al. (2014). Dropout: a simple way to prevent neural networks from overfitting.
The journal of machine learning research, 15(1), 1929–1958.
Commandeur, F. , et al. (2018). Deep learning for quantification of epicardial and thoracic
adipose tissue from non-contrast CT. IEEE transactions on medical imaging, 37(8), 1835–1846.
Zhang, W. , et al. (2015). Deep convolutional neural networks for multimodality isointense infant
brain image segmentation. NeuroImage, 108, 214–224.
Bar, Y. et al. (2015, March). Deep learning with non-medical training used for chest pathology
identification. In Medical Imaging 2015: Computer-Aided Diagnosis (Vol. 9414, p. 94140V).
International Society for Optics and Photonics.
Bergamo, A. et al. (2011). Picodes: Learning a compact code for novel-category recognition.
Advances in neural information processing systems, 24.
Moeskops, P. et al (2016). Deep learning for multi-task medical image segmentation in multiple
modalities. In International Conference on Medical Image Computing and Computer-Assisted
Intervention (pp. 478–486). Springer, Cham.
Prasoon, A. et al. (2013). Deep feature learning for knee cartilage segmentation using a
triplanar convolutional neural network. In International conference on medical image computing
and computer-assisted intervention (pp. 246–253). Springer, Berlin, Heidelberg.
Roth, H. R. et al. (2014, September). A new 2.5 D representation for lymph node detection
using random sets of deep convolutional neural network observations. In International
conference on medical image computing and computer-assisted intervention (pp. 520–527).
Springer, Cham.
Simonyan, & Zisserman . (2014). Very deep convolutional networks for large-scale image
recognition. arXiv preprint arXiv: 1409.1556.
Fakoor, R. , et al. (2013, June). Using deep learning to enhance cancer diagnosis and
classification. In Proceedings of the international conference on machine learning (Vol. 28, pp.
3937–3949). ACM, New York USA.
Kamnitsas, K. , et al. (2017). Efficient multi-scale 3D CNN with fully connected CRF for accurate
brain lesion segmentation. Medical image analysis, 36, 61–78.
Chen, J. , et al. (2016). Combining fully convolutional and recurrent neural networks for 3d
biomedical image segmentation. Advances in neural information processing systems, 29.
Long, J. , et al. (2015). Fully convolutional networks for semantic segmentation. In Proceedings
of the IEEE conference on computer vision and pattern recognition (pp. 3431–3440).
Gibson, E. , et al. (2017). Towards image-guided pancreas and biliary endoscopy: automatic
multi-organ segmentation on abdominal CT with dense dilated networks. In International
Conference on Medical Image Computing and Computer-Assisted Intervention (pp. 728–736).
Springer, Cham.
Zhou, X. , et al. (2017). Deep learning of the sectional appearances of 3D CT images for
anatomical structure segmentation based on an FCN voting method. Medical physics, 44(10),
5221–5233.
Zhou, X. , et al. (2016). Three-dimensional CT image segmentation by combining 2D fully
convolutional network with 3D majority voting. In Deep Learning and Data Labeling for Medical
Applications (pp. 111–120). Springer, Cham.
Christ, P. F. , et al. (2016). Automatic liver and lesion segmentation in CT using cascaded fully
convolutional neural networks and 3D conditional random fields. In International conference on
medical image computing and computer-assisted intervention (pp. 415–423). Springer, Cham.
Gibson, E. , et al. (2017, March). Deep residual networks for automatic segmentation of
laparoscopic videos of the liver. In Medical Imaging 2017: Image-Guided Procedures, Robotic
Interventions, and Modeling (Vol. 10135, pp. 423–428). SPIE.
Zhou, X. Y. , et al. (2018, October). Towards automatic 3D shape instantiation for deployed
stent grafts: 2D multiple-class and classimbalance marker segmentation with equally-weighted
focal U-Net. In 2018 IEEE/RSJ International Conference on Intelligent Robots and Systems
(IROS) (pp. 1261–1267 ). IEEE.
Zeng, G. , et al. (2018, April). Multi-stream 3D FCN with multiscale deep supervision for multi-
modality isointense infant brain MR image segmentation. In 2018 IEEE 15th International
Symposium on Biomedical Imaging (ISBI 2018) (pp. 136–140). IEEE.
Wang, J. , et al. (2016, October). A deep learning approach for semantic segmentation in
histology tissue images. In International Conference on Medical Image Computing and
Computer-Assisted Intervention (pp. 176–184). Springer, Cham.
Yu, L. , et al. (2016). Automated melanoma recognition in dermoscopy images via very deep
residual networks. IEEE transactions on medical imaging, 36(4), 994–1004.
He, K. , et al. (2016). Deep residual learning for image recognition. In Proceedings of the IEEE
conference on computer vision and pattern recognition (pp. 770–778).
He, K. , et al. (2016, October). Identity mappings in deep residual networks. In European
conference on computer vision (pp. 630–645). Springer, Cham.
Zagoruyko and Komodakis . (2016). Wide residual networks. arXiv preprint arXiv:1605.07146.
Chen, H. , et al. (2018). VoxResNet: Deep voxelwise residual networks for brain segmentation
from 3D MR images. NeuroImage, 170, 446–455.
Golan, R. , et al. (2016, July). Lung nodule detection in CT images using deep convolutional
neural networks. In 2016 international joint conference on neural networks (IJCNN) (pp.
243–250). IEEE.
Shen, D. et al. (2017). Deep learning in medical image analysis. Annual review of biomedical
engineering, 19, 221–248.
Feng, X. , et al. (2017). Discriminative localization in CNNs for weakly-supervised segmentation
of pulmonary nodules. In International conference on medical image computing and computer-
assisted intervention (pp. 568–576). Springer, Cham.
Arimura, Hidetaka (2017). Image Computing and Computer-Assisted Intervention. Springer,
2017, pp 568–576
Dou, Q. , et al. (2017). 3D deeply supervised network for automated segmentation of volumetric
medical images. Medical image analysis, 41, 40–54.
Baumgartner, C. F. , et al. (2017). An exploration of 2D and 3D deep learning techniques for
cardiac MR image segmentation. In International Workshop on Statistical Atlases and
Computational Models of the Heart (pp. 111–119). Springer, Cham.
Cicek, O. , et al. (2016). 3D U-Net: learning dense volumetric segmentation from sparse
annotation. In International conference on medical image computing and computer-assisted
intervention (pp. 424–432). Springer, Cham.
Kawahara, J. , et al. (2016). Deep features to classify skin lesions. In 2016 IEEE 13th
international symposium on biomedical imaging (ISBI) (pp. 1397–1400). IEEE.
Ioffe. and Szegedy . (2015). Batch normalization: Accelerating deep network training by
reducing internal covariate shift. In International conference on machine learning (pp. 448–456).
PMLR.
Zeng, G. , et al. (2017). 3D U-net with multi-level deep supervision: fully automatic
segmentation of proximal femur in 3D MR images. In International workshop on machine
learning in medical imaging (pp. 274–282). Springer, Cham.
Urban, G. , et al. (2014). Multi-modal brain tumor segmentation using deep convolutional neural
networks. MICCAI BraTS (brain tumor segmentation) challenge. Proceedings, winning
contribution, 31–35.
Ettinger, D. S. , et al. (2012). Non–Small Cell Lung Cancer. Journal of the National
Comprehensive Cancer Network, 10(10), 1236–1271.
Eisenhauer, E. A. , et al. (2009). New response evaluation criteria in solid tumours: Revised
RECIST guideline (version 1.1). , 45(2), 0–247.
Aerts, H. J. , et al. (2014). Decoding tumour phenotype by noninvasive imaging using a
quantitative radiomics approach. Nature communications, 5(1), 1–9.
Coroller, T. P. , et al. (2017). Radiomic-based pathological response prediction from primary
tumors and lymph nodes in NSCLC. Journal of Thoracic Oncology, 12(3), 467–476.
Coroller, T. P. , et al. (2016). Radiomic phenotype features predict pathological response in
non-small cell lung cancer. Radiotherapy and oncology, 119(3), 480–486.
Coroller, T. P. , et al. (2015). CT-based radiomic signature predicts distant metastasis in lung
adenocarcinoma. Radiotherapy and Oncology, 114(3), 345–350.
Hosny, A. , et al. (2018). Deep learning for lung cancer prognostication: a retrospective multi-
cohort radiomics study. PLoS medicine, 15(11), e1002711.
Albain, K. S. , et al. (2005). Phase III study of concurrent chemotherapy and radiotherapy
(CT/RT) vs CT/RT followed by surgical resection for stage IIIA (pN2) non-small cell lung cancer
(NSCLC): outcomes update of North American Intergroup 0139 (RTOG 9309). Journal of
Clinical Oncology, 23(16_suppl), 7014–7014.
Tsujino, K. , et al. (2003). Predictive value of dose-volume histogram parameters for predicting
radiation pneumonitis after concurrent chemoradiation for lung cancer. International Journal of
Radiation Oncology* Biology* Physics, 55(1), 110–115.
Hellmann, M. D. , et al. (2014). Pathological response after neoadjuvant chemotherapy in
resectable non-small-cell lung cancers: proposal for the use of major pathological response as a
surrogate endpoint. The lancet oncology, 15(1), e42–e50.
Parmar, C. , et al. (2014). Robust radiomics feature quantification using semiautomatic
volumetric segmentation. PloS one, 9(7), e102107.
Ronneberger, O. , et al. (2015). U-net: Convolutional networks for biomedical image
segmentation. In International Conference on Medical image computing and computer-assisted
intervention (pp. 234–241). Springer, Cham.
Litjens, G. , et al. (2017). A survey on deep learning in medical image analysis. Medical image
analysis, 42, 60–88.
Sun, Y. , et al. (2014). Deep learning face representation from predicting 10,000 classes. In
Proceedings of the IEEE conference on computer vision and pattern recognition (pp.
1891–1898).
Shin, H. C. , et al. (2016). Deep convolutional neural networks for computer-aided detection:
CNN architectures, dataset characteristics and transfer learning. IEEE transactions on medical
imaging, 35(5), 1285–1298.
Yue-Hei Ng, J. , et al. (2015). Beyond short snippets: Deep networks for video classification. In
Proceedings of the IEEE conference on computer vision and pattern recognition (pp.
4694–4702).
Che, Z. , et al. (2018). Recurrent neural networks for multivariate time series with missing
values. Scientific reports, 8(1), 1–12.
Kyunghyun C. , et al. (2014) Learning phrase representations using RNN encoder–decoder for
statistical machine translation. In: Proceedings of Conference on Empirical Methods in Natural
Language Processing (EMNLP); Doha, Qatar. Stroudsburg (PA): Association for Computational
Linguistics; 2014. p. 1724–1734.
Huynh, E. , et al. (2016). CT-based radiomic analysis of stereotactic body radiation therapy
patients with lung cancer. Radiotherapy and Oncology, 120(2), 258–266.
Hua, K. L. , et al. (2015). Computer-aided classification of lung nodules on computed
tomography images via deep learning technique. OncoTargets and therapy, 8.
Coroller, T. P. , et al. (2015). CT-based radiomic signature predicts distant metastasis in lung
adenocarcinoma. Radiotherapy and Oncology, 114(3), 345–350.
Ioffe and Szegedy, et al. (2015). Batch normalization: Accelerating deep network training by
reducing internal covariate shift. In International conference on machine learning (pp. 448–456).
PMLR.
Wang, G. (2016). A perspective on deep imaging. IEEE access, 4, 8914–8924.
Xu, Y. , et al. (2019). Deep learning predicts lung cancer treatment response from serial medical
imaging. Clinical Cancer Research, 25(11), 3266–3275.
Issues and Challenges in Bioinformatics Tools for Clinical Trials
Marturano, A. (2009). Bioinformatics and ethics. Bioethics, 23(7).
Lewis, J. , & Bartlett, A. (2013). Inscribing a discipline: Tensions in the field of bioinformatics.
New Genetics and Society, 32(3), 243–263.
Gibson, G. , & Muse, S. V. (2009). A primer of genome science (No. 575 GIB).
Tavani, H. T. (2013) Ethics and technology: Controversies, questions, and strategies for ethical
computing. New York: Wiley.
“MSc in Bioinformatics Master in Bioinformatics Fac. Biocincies, UAB”
http://MScBioinformatics.uab.cat Domestic. Accessed June 08,2016.
“Online Education Kit: Bioinformatics: Introduction.” National Human Genome Research
Institute, 18 Mar. 2013. Web. 09 June 2016.
Amer, S. (2017). Ethical concerns regarding the use of bioinformatics and computational
genomics. In Proceedings of the International Conference on e-Learning, e-Business,
Enterprise Information Systems, and e-Government (EEE) (pp. 58–62). The Steering
Committee of The World Congress in Computer Science, Computer Engineering and Applied
Computing (WorldComp).
Rashidi, H. H. , and Buehler, L. K. (1999). Bioinformatics basics: applications in biological
science and medicine. CRC press.
Wang, X. , & Liotta, L. (2011). Clinical bioinformatics: a new emerging science. Journal of
clinical bioinformatics, 1(1), 1–3.
Butte, A. J. (2008). Translational bioinformatics: coming of age. Journal of the American Medical
Informatics Association, 15(6), 709–714.
Sarkar et al . (2011). Translational bioinformatics: linking knowledge across biological and
clinical realms. Journal of the American Medical Informatics Association, 18(4), 354–357.
Murphy et al . (2010). Serving the enterprise and beyond with informatics for integrating biology
and the bedside (i2b2). Journal of the American Medical Informatics Association, 17(2),
124–130.
NETTAB Workshops . [http://www.nettab.org/]. Kimball R: The Information Warehouse Toolkit:
practical strategies for creating dimensional Information warehouses. New York, NY: John Wiley
& Sons, Inc;, Moment 2002.
Shortliffe, E. , et al. (2001). “Biomedical Informatics; Computer Applications in Health Care and
Biomedicine”. BioMed Eng OnLine 5, 61. https://doi.org/10.1186/1475-925X-5-61
Bergeron, B. P. (2003). Bioinformatics computing. Prentice Hall Professional.
Ihaka, R. , & Gentleman, R. (1996). R: a language for data analysis and graphics. Journal of
computational and graphical statistics, 5(3), 299314.
Van’t et al . (2002). Gene expression profiling predicts clinical outcome of breast cancer. nature,
415(6871), 530–536.
Sujansky, W. (2001). Heterogeneous database integration in biomedicine. Journal of biomedical
informatics, 34(4), 285–298.
Donelson et al. (2004). The BioMediator system as a data integration tool to answer diverse
biologic queries. In Medinfo 2004 (pp. 768772). IOS Press.
Mork et al. (2001). A model for data integration systems of biomedical data applied to online
genetic databases. In Proceedings of the AMIA Symposium (p. 473). American Medical
Informatics Association.
Mork et al. (2002). PQL: a declarative query language over dynamic biological schemata. In
Proceedings of the AMIA Symposium (p. 533). American Medical Informatics Association.
Shaker et al. (2002). A rule driven bi-directional translation system for remapping queries and
result sets between a mediated schema and heterogeneous data sources. In Proceedings of
the AMIA Symposium (p. 692). American Medical Informatics Association.
Shaker et al. (2004, August). The biomediator system as a tool for integrating biologic
databases on the web. In Proceedings of the Workshop on Information Integration on the Web.
Lu, Y. (2003). Roadmap for tool support for collaborative ontology engineering.
Mei et al. (2003). Expression array annotation using the BioMediator biological data integration
system and the BioConductor analytic platform. In AMIA Annual Symposium Proceedings (Vol.
2003, p. 445). American Medical Informatics Association.
Rosse and Mejino (2003). A reference ontology for biomedical informatics: the Foundational
Model of Anatomy. Journal of biomedical informatics, 36(6), 478–500.
Tuttle and Nelson (1994). The role of the UMLS in ‘storing’and ‘sharing’across systems.
International journal of bio-medical computing, 34(1–4), 207–237.
Bodenreider et al. (2002). Evaluation of the UMLS as a terminology and knowledge resource for
biomedical informatics. In Proceedings of the AMIA Symposium (p. 61). American Medical
Informatics Association.
Klein et al . (2001). Integrating genotype and phenotype information: an overview of the
PharmGKB project. The pharmacogenomics journal, 1(3), 167–170.
PharmGKB , http://www.pharmgkb.org.
Friedman, C. P. , & Wyatt, J. C. (1997). Studying Clinical Information Resources. In Evaluation
Methods in Medical Informatics (pp. 41–64). Springer, New York, NY.
[Langmead] Langmead, Ben . “What Are Genomics and ComputationalGenomics?” Johns
Hopkins. http://www.cs.jhu.edu/langmea/resources/lecturenotes/genomicscompgenomics.pdf.
He et al . (2005). Advances In Bioinformatics And Its ApplicationsProceedings Of The
International Conference (Vol. 8). World Scientific.
Yohe et al. (2015). Standards for clinical grade genomic databases. Archives of pathology &
laboratory medicine, 139(11), 1400–1412.
Gersbach, C. A. (2014). Genome engineering: the next genomic revolution. Nature methods,
11(10), 1009–1011.
Michael, T. P. , & Jackson, S. (2013). The first 50 plant genomes. The plant genome, 6(2).
Key et al . (2008). Genetically modified plants and human health. Journal of the Royal Society
of Medicine, 101(6), 290–298.
Lesk, A. (2019). Introduction to bioinformatics. Oxford university press.
Icd-9.[http://www.cdc.gov/nchs/icd/icd9.htm].
Snomed-Ct. [http://www.ihtsdo.org/snomed-ct/].
CPT - Common procedural terminology.
[http://en.wikipedia.org/wiki/CommonProceduralTerminology].
HCPCS-Health care current arrangement coding system.
[http://www.cms.gov/Medicare/Coding/MedHCPCSGenInfo/index.html].
NDC - National Drug Code. [http://en.wikipedia.org/wiki/NationalDrugCode].
LOINC - Sensible Observation Identifiers Names and Codes. [http://loinc.org/].
European Committee for Standardization (CEN) - Semantic interoperability in the electronic
health memoir communication. [http://www.en13606.org/].
HL7 (Health Level Seven) Version 3 Standard: Foundation (Reference Databases Model,
Statistics Types and Vocabulary).
[http://www.hl7.org/v3ballot/html/welcome/environment/index.html].
Dolin et al . (2006). HL7 clinical document architecture, release 2. Journal of the American
Medical Informatics Association, 13(1), 30–39.
Langville and Meyer . (2011). Google’s PageRank and beyond. In Google’s PageRank and
Beyond. Princeton university press.
Baeza-Yates et al . (2011). Trends in search interaction. In Search computing (pp. 26–32).
Springer, Berlin, Heidelberg.
Masseroli et al . (2011). Bio-Search Computing: Integration and global ranking of bioinformatics
search results. Journal of Integrative Bioinformatics, 8(2), 148–156.
Kesh and Raghupathi (2004). Critical issues in bioinformatics and computing. Perspectives in
health information management/AHIMA, American Health Information Management
Association, 1.
Koonin, E. V. (2003). Comparative genomics, minimal gene-sets and the last universal common
ancestor. Nature Reviews Microbiology, 1(2), 127–136.
Singh, V. (2012) “What Is the Human Genome Plan and What Are Its benefit and
Disadvantages?” What Is the Human Genome Plan and What Are Its benefit and
Disadvantages? PreserveArticles. Web. 09 June 2016.
Perzigian, Andrew B. (2003) “Brief Summary of Genetic Engineering and Animals.” Short
Summary of Genetic Engineering and Animals. Michigan Assert University College of Law.
Web. 09 June 2016.
Howard, H. C. , et al. (2013). The ethical introduction of genomebased information and
technologies into public health. Public Health Genomics, 16(3), 100–109.
Martensen, R. (2001). The history of bioethics: an essay review. Journal of the history of
medicine and allied sciences, 56(2), 168–175.
Elston, R. C. , et al. (2002). Biostatistical genetics and genetic epidemiology (Vol. 1). John Wiley
& Sons.
Barnetche, T. , et al. (2005). Main features of factors involved in aetiology of complex disease.
Transplant Immunology, 3(14), 255–266.
Lobo, I. (2008). Basic local alignment search tool (BLAST). Nat Educ, 1(1).
Madeira, F. , Park, Y. M. , Lee, J. , Buso, N. , Gur, T. , Madhusoodanan, N. , ... & Lopez, R.
(2019). The EMBL-EBI search and sequence analysis tools APIs in 2019. Nucleic acids
research, 47(W1), W636–W641.
Ganesan, N. , Bennett, N. F. , Velauthapillai, M. , Pattabiraman, N. , Squier, R. , &
Kalyanasundaram, B. (2005). Web-based interface facilitating sequence-to-structure analysis of
BLAST alignment reports. Biotechniques, 39(2), 186–188.
Branco, I. , & Choupina, A. (2021). Bioinformatics: new tools and applications in life science and
personalized medicine. Applied Microbiology and Biotechnology, 105(3), 937–951.
Burge, C. , & Karlin, S. (1997). Prediction of complete gene structures in human genomic DNA.
Journal of molecular biology, 268(1), 78–94.
Parra Farré, G. , Blanco, E. , & Guigó Serra, R. (2000). GeneID in “Drosophila”. Genome
Research. 2000; 10 (4): 511–515.
Mitra, A. , Kesarwani, A. K. , Pal, D. , & Nagaraja, V. (2011). WebGeSTer DB—a transcription
terminator database. Nucleic acids research, 39(suppl_1), D129–D135.
Weckx, S. , Del-Favero, J. , Rademakers, R. , Claes, L. , Cruts, M. , De Jonghe, P. , & De Rijk,
P. (2005). novoSNP, a novel computational tool for sequence variation discovery. Genome
research, 15(3), 436–442.
Münch, R. , Hiller, K. , Grote, A. , Scheer, M. , Klein, J. , Schobert, M. , & Jahn, D. (2005).
Virtual Footprint and PRODORIC: an integrative framework for regulon prediction in
prokaryotes. Bioinformatics, 21(22), 4187–4189.
Gasteiger, E. , Hoogland, C. , Gattiker, A. , Wilkins, M. R. , Appel, R. D. , & Bairoch, A. (2005).
Protein identification and analysis tools on the ExPASy server. The proteomics protocols
handbook, 571–607.
Allen, J. E. , & Salzberg, S. L. (2005). JIGSAW: integration of multiple sources of evidence for
gene prediction. Bioinformatics, 21(18), 35963603.
Madeira, F. , Park, Y. M. , Lee, J. , Buso, N. , Gur, T. , Madhusoodanan, N. , ... & Lopez, R.
(2019). The EMBL-EBI search and sequence analysis tools APIs in 2019. Nucleic acids
research, 47(W1), W636–W641.

Advancement in Artificial Intelligence: Insights and Future Vision for the

Pharmacy Profession
Caamaño, F. , Ruano, A. , Figueiras, A. , Gestal-Otero, J.J. (2002) Data collection methods for
analyzing the quality of the dispensing in pharmacies. Pharm World Sci. 24, 217e223.
Toklu, H.Z. , Akici, A. , Oktay, S. , Cali, S. , Sezen, S.F. , Keyer-Uysal, M. (2010) The pharmacy
practice of community pharmacists in Turkey. Marmara Pharm J. 14, 53e60.
Van Mil, F. (2002) Pharmacy and health care. Pharm World Sci. 24, 213.
Ferreri, S.P. , Cross, B. , Hanes, S.D. , Jenkins, T. , Meyer, D. , Pittenger, A. (2017) Academic
pharmacy: where is our influence? Am J Pharm Educ. 81, 4.
Hughes, L.D. , Welch, L.H. , Hannings, A. (2014) Relationship between StrengthsFinder 2.0
Leadership domains and student pharmacist perceived capabilities to perform leadership skills.
115th Annual Meeting of the American Association of Colleges of Pharmacy, Grapevine, Texas,
July 26–30, 2014. Am J Pharm Educ. 78, 5.
Bloom, T.J. (2016) Comparison of StrengthsFinder signature themes in PharmD and DO
students. 117th Annual Meeting of the American Association of Colleges of Pharmacy,
Anaheim, California. Am J Pharm Educ. 80, 5.
Janke, K.K. , Farris, K.B. , Kelley, K.A. , et al. (2015) StrengthsFinder signature themes of talent
in doctor of pharmacy students in five Midwestern pharmacy schools. Am J Pharm Educ. 79, 4.
Rath, T. , Conchie, B. (2008) Strengths Based Leadership. New York, NY: Gallup Press.
Caamaño, F. , Alvarez, R. , Khoury, M. (2008) The community pharmacists and their practice as
health care providers. Gac Sanit. 22 : 385.9.
Role of Dispensers in Promoting Rational Drug Use . Internatıonal Network of Rational Drug
Use. World Health Organization, 2000.
The Role of Education in the Rational Use of Medicines . Internatıonal Network of Rational Drug
Use. World Health Organization, 2006.
Benjamin, D.M. (2003) Reducing medication errors and increasing patient safety: case studies
in clinical pharmacology. J Clin Pharmacol. 43, 768e783.
Dessing, R. P. (2000) Ethics applied to pharmacy practice. Pharm World Sci. 22, 10e16.
Strand, L.M. , Cipolle, R.J. , Morley, P.C. (1992) Pharmaceutical Care: An Introduction.
Michigan: Upjohn Co., 14e29.
Strand, L.M. , Morley, P.C. , Cipolle, R.J. , Ramsey, R. , Lamsam, G.D. (1990) Drug-related
problems; their structure and function. Dicp. 24, 1093e1097.
Hepler, C.D. , Strand, L.M. Opportunities and responsibilities in pharmaceutical care. Am J
Hosp Pharm. 47, 533e543.
Farris, K.B. , Fernandez-Llimos, F. , Benrimoj, S.I. (2005) Pharmaceutical care in community
pharmacies: practice and research from around the world. Ann Pharmacother. 39, 1539e1541.
Azhar, S. , Hassali, M.A. , Ibrahim, M.I. , Ahmad, M. , Masood, I. , Shafie, A.A. (2009) The role
of pharmacists in developing countries: the current scenario in Pakistan. Hum Resour Health. 7,
54.
Toklu, H.Z. , Ayanoglu-Dulger, G. , Gumusel, B. , Yaris, E. , Kalyoncu, N.I. , Akici, A. (2010)
Developing a model checklist for the evaluation of the dispensing scores in the pharmacy. Basic
Clin Pharmacol Toxicol. 107, 617e618.
Toklu, H.Z. , Dulger, G. , Yaris, E. , Gumusel, B. , Akici, A. (2009) First impressions from a short
training course in rational use of drugs for the pharmacologists in the pharmacy schools in
Turkey. Value Health. 12, A249.
Toklu, H.Z. (2013) Problem based pharmacotherapy teaching for pharmacy students and
pharmacists. Curr Drug Deliv. 10, 67e70.
Sahu, A. , Mishra, J. , Kushwaha, N. (2021). Artificial Intelligence (AI) in Drugs and
Pharmaceuticals. Combinatorial chemistry & high throughput screening.
Kathleen, W. (2020) The Increasing Use of AI In the Pharmaceutical Industry. Available at:
https://www.forbes.com/sites/cognitiveworld/2020/12/26/the-increasing-use-of-ai-in-the-
pharmaceutical-industry/?sh=693bed6e4c01 [Accessed on 6 July 2022].
Toward an Optimal Future: Priorities for Action, Research Report, Pharmacy Thought
Leadership Summit by Intergage Consulting Group Inc. available at:
https://www.pharmacists.ca/cpha-ca/assets/File/pharmacyin-
canada/Thought%20Leadership%20Summit%20Research%20Report_01.pdf [ Accessed on 6
July 2022.
McGrail, S. (2021) AI in the Pharma Industry: Current Uses, Best Cases, Digital Future, 2021.
Available at: https://pharmanewsintel.com/news/ai-in-the-pharma-industry-current-uses-best-
cases-digital-future [last accessed on 5 July 2022 ].
Goyal, K. (2022) Artificial Intelligence in Pharmaceutical Industry: 8 Exciting Applications in
2022. Available at: https://www.upgrad.com/blog/artificial-intelligence-in-pharmaceutical [last
accessed on 5 July 2022 ].
Jorgenson, D. , Penm, J. , MacKinnon, N.J. , Smith, J. (2017) Future vision for the pharmacy
profession. Can Pharm J (Ott) 150, 4.
Advisory Panel on Healthcare Innovation . Unleashing Innovation: Excellent Healthcare for
Canada. 2015. Available at: http://www.healthycanadians.gc.ca/publications/health-system-
systemesante/summary-innovation-sommaire/index-eng.php [Last accessed on 2 July 2022 ].
Avalere Healthcare LLC . Exploring Pharmacists’ Role in a Changing Healthcare Environment.
(2014) Available at: http://www.nacds.org/pdfs/comm/2014/pharmacist-role.pdf.
Improving Care Transitions: Optimizing Medication, March 2012, APhA/ASHP and After
Hospitalization: A Dartmouth Atlas Report on Readmissions Among Medicare Beneficiaries.
International Pharmacy Federation . Advanced Practice and Specialization in Pharmacy: Global
Report. (2015) Retrieved from: https://www.ucl.ac.uk/pharmacy/documents/fip-global-report-
2015.
Pharmacy Practice+Community Pharmacy Trends & Insights 2015. Toronto (ON): Rogers
Publishing.
Baronzio, G. (2015) Overview of methods for overcoming hindrance to drug delivery to tumors,
with special attention to tumor interstitial fluid. Front. Oncol. 5, 165.
Achenbach, J. (2011) Computational tools for polypharmacology and repurposing. Fut. Med.
Chem. 3, 961–968.
Harrer, S. , Shah, P. , Antony, B. , Hu, J. (2019) Artificial intelligence for clinical trial design.
Trends Pharmacol Sci. 40, 577–591.
Karekar, S.R. , Vazifdar, A.K. (2021) Current status of clinical research using artificial
intelligence techniques: A registry-based audit. Perspect Clin Res. 12, 48–52.
Jiang, F. , Jiang, Y. , Zhi, H. , Dong, Y. , Li, H. , Ma, S. , et al. (2017) Artificial intelligence in
healthcare: Past, present and future. Stroke Vasc Neurol. 2, 230–243.
Artificial Intelligence in Pharma, Available at: https://www.pharmaceutical-
technology.com/artificial-intelligence-in-pharma/ [accessed on 5 July 2022 ].
Basu, K. , Sinha, R. , Ong, A. , Basu, T. (2020) Artificial Intelligence: How is It Changing Medical
Sciences and Its Future? Indian J Dermatol. 65, 5, 365–370.
Parisis, N. , Medical writing in the era of artificial intelligence, Medical Writing, 2019, 28 (4), 4–9.