BIOTECHNOLOGY OPERATIONS PRINCIPLES AND PRACTICES SECOND EDITION【2025|PDF|Epub|mobi|kindle电子书版本百度云盘下载】

BIOTECHNOLOGY OPERATIONS PRINCIPLES AND PRACTICES SECOND EDITIONPDF格式电子书版下载

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1.Introduction to Biotechnology Operations：Planning for Success1

Biotechnology Operations1

Marketing，Financial，and Business Considerations for Development4

Product Development Planning7

Rationale for Product Development Planning7

The Targeted Product Profile10

The Product Development Plan16

Clinical Development Planning18

Project Management Planning19

Regulatory Planning20

Nonclinical Planning22

Biomanufacturing Planning23

Quality Control Planning24

Quality Systems and Quality Assurance Planning26

Additional Elements of Product Planning26

Summary of Planning for Success28

2.Project Management29

Biotechnology and Project Management29

Background of Project Management31

Project Management Plan32

The Project Management Environment34

Project Objectives and Schedules36

Sociotechnical Considerations37

Participants in Project Management37

Project Management in Biotechnology Operations41

Establishing Project Management41

The Work Breakdown Structure42

Forming a Project Team and Hands-on Project Management46

Team Dynamics46

Communication and Feedback49

Project Risk Assessment and Management51

Metrics and Tracking Progress53

Resources：Planning and Usage54

Human Factors in Project Management55

Project Completion57

Project Management with Contracts and Collaborations59

Virtual Teams60

Tools for Effective Project Management61

Summary of Project Management in Biotechnology Development64

3.Regulatory Affairs65

The U.S.Food and Drug Administration：Law and Regulations for Biopharmaceuticals65

Historical Basis for FDA Regulation65

Regulatory Organization of the FDA66

Food and Drug Law，Regulation，and Guidance71

FDA-Regulated Products71

Biologics72

Drugs75

Medical Devices76

Combination Products77

Other Classes of Biotechnology Products and Their Review at the FDA79

Products for Veterinary Use79

Cosmetics，Food，Dietary Supplements，Homeopathic，or Nutritional Products79

FDA Regulatory Information and Resources：Regulatory Intelligence81

Regulatory Operations for FDA Applications84

Regulatory Planning and the Regulatory Environment84

Risk Versus Benefit84

Applications Seeking FDA Investigational Use or Marketing Approval87

Investigational Use Applications.The Investigational New Drug Application89

Common Technical Document91

Electronic Submission of a CTD92

Marketing Applications：BLA and NDA96

Medical Device Applications.510（k） and PMA99

Special Documents，Pathways，or Exemptions101

Generic Drugs and Biosimiliar or Follow-on Biologics104

Other Regulatory Activities105

Public Meetings and Advisory Committees105

Postmarketing Requirements and Activities107

Advertising and Promotion108

Summary of Regulatory Affair Activities in Biotechnology Operations109

References111

4.Regulatory Compliance113

Regulatory Compliance113

Quality Systems to Meet Regulatory Compliance113

Compliance and Quality Systems113

Current Good Manufacturing Practices for Manufacture and Quality Control114

Current Good Laboratory Practices for Nonclinical Laboratory Studies117

Current Good Clinical Practices for Clinical Studies117

Compliance for Biopharmaceuticals：Other Regulations of Importance119

Compliance for Import of Biopharmaceuticals into the United States119

Compliance for Medical Devices120

Inspection and Enforcement120

Inspections121

Enforcement Actions123

Product Liability125

Compliance with Non-FDA Regulations：International，National，State，and Local126

International and Foreign National Regulatory Authorities for Medical Biotechnology Products126

Transporting Infectious or Otherwise Hazardous Materials132

Importing，Possessing，or Transferring Controlled Biotechnology Materials134

The Public Health Security and Bioterrorism Preparedness and Response Act of 2002136

Importation or Exportation of Biotechnology Products for the Purpose of Treatment of Diseases in Humans137

Occupational Health and Safety140

Environmental Regulations in Biotechnology141

Genetically Modified Organisms or Molecules142

International Diligence in Biotechnology Operations144

Summary of Regulatory Compliance146

Summary of Non-FDA Compliance147

References148

5.Quality Systems149

Overview of Quality in Biotechnology149

History：Evolution of Quality Concepts and Practices150

Quality Systems Approach to Product Development153

Planning a Quality System156

Defining Objectives and Ensuring Management Support156

The Quality Manual156

The Quality Plan157

Hallmarks of Quality：Fundamental Criteria for Building Effective Quality Systems159

Management Responsibility160

Defined Quality System162

QbD and Design Control163

Quality by Design163

Design Control164

Design Change169

Contractor，Vendor，and Consultant Control169

Product Identification and Traceability171

Process Control172

Environmental Controls173

Inspection or Testing （Quality Control）173

Release of Material，Service，or Product174

Change Control and Corrective or Preventive Actions175

Packaging and Labeling176

Preservation，Storage，and Handling176

Servicing178

Customer Concerns and Adverse Event Reports178

Document Control178

Training178

Auditing179

The Quality Assurance Unit180

Manage the Quality Assurance Function181

Control Documents and Manage the Documentation System182

Investigate Situations：Manage and Control Change184

Ensure Qualified and Trained Staff184

Perform Audits185

Initiate a Quality System for a Biotechnology Operation188

Unique and Effective Approaches to Quality Management190

Risk-Based Approaches to Quality Systems190

Total Quality Management190

Six Sigma191

Statistics in Quality Assurance191

Quality Systems for Research191

Resolving Quality Issues or Problems192

Summary of Quality Systems193

References194

6.Biomanufacture195

Overview of Biomanufacturing Requirements195

Design in Biomanufacture196

Technical Considerations for Biomanufacture200

Phases and Scale-up：The Biomanufacturing Life Cycle201

Raw Material Considerations205

Compliance and Quality in Biomanufacture：Current Good Manufacturing Practices207

Biomanufacturing Processes for Biotechnology Products209

Expression of Recombinant Proteins and Nucleic Acids209

Production of Recombinant Molecules from Expression Vectors209

Genes，Vectors，and Host Cells210

Bacterial Cell Expression Systems212

Yeast Cell Expression Systems213

Mammalian or Insect Cell Expression Systems213

Production of Master Cell Banks and Working Cell Banks216

Biomanufacture of Recombinant Proteins217

Planning Production of a Recombinant Protein217

Upstream Process：Production by Bacterial or Yeast Cell Fermentation218

Upstream Process：Production by Mammalian or Insect Cell Culture220

Upstream Process：Recovery221

Downstream Process：Purification222

In-Process Testing and Analysis of Bulk Substance230

Production of Bacterial Plasmid DNA231

Production of Live Recombinant Organisms：Bacteria and Virus232

Production of Products Composed of Mammalian Somatic Cells or Tissues234

Production of Cellular Products Derived from Pluripotent （Stem） Cells236

Production of Biological Molecules by Transgenic Animals or Plants238

Production of Biologically Active Lipids，Glycolipids，and Complex Carbohydrates245

Production of Biologically Active Peptides245

Production of Combination Products：Biopharmaceutical with a Drug or Medical Device247

FP：Formulation，Fill，Finish，and Labeling248

Biomanufacturing Facilities，Utilities，and Equipment253

Facility Design Considerations253

The Facility and Utilities：A Controlled Environment254

Operation of Clean Work Areas for Biomanufacture255

Biomanufacturing Equipment257

Contract Manufacturing Options257

Validation of Biomanufacturing Facilities，Utilities，Equipment，and Processes259

Summary of Biomanufacture261

References262

7.Quality Control263

Quality Control Overview263

Definition of Product Attributes265

Analytical Methods to Measure Attributes266

Traits of Analytical Methods267

Drafting a Certificate of Analysis （Bulk Substance）267

Selection of Analytical Methods270

Development of Specifications277

Entering Test Results282

Certificate of Analysis for Drug Product282

In-Process Testing285

Analytical Methods286

Additional Analytical Tools and Concepts295

Quality Control of Cell Banks297

Samples and Sampling298

Analytical Controls and Reference Standards299

Test Failures，Out-of-Specification Results，and Retesting300

Testing for Product Stability302

Quality Control Testing of Raw Materials308

Quality Control and the Manufacturing Environment310

Qualification，Validation，and Verification of Analytical Methods312

Application of Statistics in Assay Performance and Validation317

Summary of Quality Control318

References319

8.Nonclinical Studies321

Nonclinical Studies and Risk Assessment321

Biopharmaceutical Delivery，Pharmacokinetics，and Pharmacodynamics323

Product Delivery to the Body323

Adsorption，Distribution，Elimination，and Metabolism （ADME）325

Absorption325

Distribution325

Metabolism and Biotransformation327

Excretion328

Pharmacokinetics and Pharmacodynamics328

Application of Pharmacokinetics and Pharmacodynamics in Biopharmaceutical Development333

Safety Assessment of Biopharmaceuticals336

Toxicology336

Design of a Safety Assessment Program337

In Vitro Screens：Surrogate Measures of Toxicity340

In Vivo Safety Testing of Biopharmaceuticals342

Animal Model Development342

Test Product Formulations，Routes of Delivery，and Dosing Designs344

Protocols and Performance of Biopharmaceutical Safety Studies in Animals346

Elements of a Nonclinical Study Design347

Nonclinical Safety Testing351

Acute Toxicity Testing351

Subchronic and Chronic Toxicity Testing356

Reproductive，Developmental，and Teratogenicity Toxicity Testing359

Carcinogenicity Testing360

Immunotoxicology361

Genetic Toxicology363

Tissue Binding or Local Tissue Tolerance367

Quality of Nonclinical Studies：Current Good Laboratory Practices368

Summary of Nonclinical Studies369

References370

9.Clinical Trials371

Introduction to Clinical Trials371

Background of Clinical Research373

Introduction373

Historical Information on Clinical Trials374

Organization of Clinical Research375

Phases of Clinical Trials375

The Science of Clinical Research376

Quality in Clinical Research and Current Good Clinical Practices377

Clinical Development Planning377

Infrastructure for a Clinical Trial：Individuals，Documents，and Investigational Product378

Design of Clinical Trials and the Clinical Protocol378

Human Subjects，Patients，and Volunteers388

The Sponsor388

The Principal Investigator and His or Her Study Staff391

Institutional Review Boards，the Process of IC，and IC Form392

Investigational Product394

Collection of Clinical Data：Case Report Forms and the Patient Diary395

Clinical Testing Laboratories396

Reporting Results of Clinical Trials：Clinical Summary Reports397

Clinical Trial Operations397

Activities Leading to a Clinical Trial398

Phase 1 Clinical Trial：First-In-Human Study400

Clinical Pharmacology Studies of Biopharmaceuticals in Human404

Phase 2 Clinical Trial：Proof-of-Concept Study405

Phase 3 Clinical Trial：Therapeutic Confirmatory406

Phase 4 Clinical Study and Risk Evaluation and Mitigation Strategy407

Clinical Trials for New Populations or Indications408

Global Clinical Trials409

Quality Systems for Clinical Trials：Current Good Clinical Practices409

Quality and cGCP in Clinical Trial Operations410

Integrity of Clinical Study Data and Documents413

Monitoring and Auditing Clinical Trials414

Ethical Behavior and the Well-Being of Clinical Trial Subjects415

Summary on Clinical Trials416

References417

Additional Readings419

Glossary425

Appendix451

Index459