Therapeutic Delivery Solutions E-Book

Chung Chow Chan

• Herausgeber: John Wiley & Sons
• Kategorie: Wissenschaft und neue Technologien
• Sprache: Englisch

Seitenzahl: 775

Veröffentlichungsjahr: 2014

Beschreibung

Provides a comprehensive review of all types of medical therapeutic delivery solutions from traditional pharmaceutical therapy development to innovative medical device therapy treatment to the recent advances in cellular and stem cell therapy development
• Provides information to potentially allow future development of treatments with greater therapeutic potential and creativity
• Includes associated regulatory requirements for the development of these therapies
• Provides a comprehensive developmental overview on therapeutic delivery solutions
• Provides overview information for both the  general reader as well as more detailed references for professionals and specialists in the field

Leseprobe

CONTENTS

Cover

Title page

Copyright page

Preface

Contributors

Acknowledgment

Section 1: Requirements and Issues encountered in Regulatory Submissions in the Pharmaceutical, Cell Therapy and Medical Device Industries

1 Challenges to Quality and Regulatory Requirement in the United States—Drugs, Medical Device, and Cell Therapy

1.1 Overview of Regulatory Requirements for Pharmaceutical, Medical Device, and Cell Therapies

1.2 Regulatory Requirements and Challenges for Pharmaceutical, Medical Device, and Cell Therapies

1.3 Initiatives in the Pharmaceutical, Medical Device, and Cell Therapy Regulatory Requirements

1.4 Current Good Manufacturing Practice Requirements for Combination Products

1.5 Conclusion

References

Section 2: Traditional Pharmaceutical Drug Therapy Development

2 Development of Tablets

2.1 Introduction

2.2 Development Plan and Milestones in TPP

2.3 Clinical Target Profile

2.4 Drug Substance Characteristics in TPP

2.5 Drug Product Characteristics in TPP

2.6 Drug Substance and Drug Product Specifications in TPP

2.7 Product Composition in TPP

2.8 Product Manufacturing in TPP

2.9 Conclusion

References

3 Formulation of Poorly Soluble Drugs for Oral Administration

3.1 Introduction

3.2 Upfront Assessments

3.3 Particle Engineering of Drug Substance

3.4 Animal Formulations and Screening of Delivery Technologies

3.5 Parallel Technology Screening Program for Human Formulations

3.6 Animal Pharmacokinetic Studies and Clinical Formulation Development

3.7 Decision Tree for Commercially Viable Delivery Systems and Formulations

3.8 Conclusion

References

Section 3: Overview, Current Trends and Strategies of Special Medical Device Development

4 Overview of Drug Delivery Devices

4.1 Introduction

4.2 Trends and Drivers for Drug Delivery Devices

4.3 Regulation of Medical Devices

4.4 The Development of Drug/Device Combination Products

4.5 Common Therapeutic Routes of Administration that Require a Medical Device

4.6 Future Direction for Drug Delivery Devices

References

5 Local Delivery of Bone Growth Factors

5.1 Applications for Local Delivery of Bone Growth Factors

5.2 Types of Bone Growth Factors

5.3 Delivery Systems

5.4 Current Status of Bone Growth Factor-Containing Products

5.5 Future Research Areas

5.6 Conclusions

References

6 Delivery of Insulin:

6.1 Introduction

6.2 The Physiology of Insulin Delivery in the Normal Human

6.3 The Early Days

6.4 Better Syringes and, for the First Time, a Meter

6.5 The DCCT Study and Why Control Matters

6.6 Implantable Insulin Pumps: The Beginning of Continuous Insulin Delivery

6.7 External Insulin Pumps: The Early Days

6.8 What to Deliver?

6.9 How to Deliver the New Insulin: Pens and Pumps

6.10 The Future: Next 10 Years

6.11 Other Uses

6.12 Conclusions

References

Section 4: Advances and Innovations in Cellular and Stem Cell Therapeutic Delivery

7 Endocrine Therapeutic Delivery

7.1 Introduction

7.2 History

7.3 Indications

7.4 Human Pancreatic Islet Processing and Transplantation

7.5 Potential Complications of Islet Transplantation

7.6 Current Outcomes

7.7 Challenges and Areas of Ongoing Research

7.8 Conclusion

7.9 Current Status of Research

References

8 Cell-Based Biologic Therapy for the Treatment of Medical Diseases

8.1 Introduction

8.2 Engineered or Processed Human Cells as Treatment Modalities

8.3 Cell-Based Immunotherapy

8.4 Conclusion

References

9 Development of Stem Cell Therapy for Medical Uses

9.1 Introduction

9.2 History of Stem Cell Development

9.3 Sources of Nonembryonic Stem Cells

9.4 Stem Cell Technology and Preparation

9.5 Regulatory Considerations and Product Testing

9.6 Application for Medical Practice

9.7 Conclusions and Outlook for the Future

References

Section 5: Analytical Support Needed For the Research and Development

10 Specification Setting and Stability Studies in the Development of Therapeutic Delivery Solution

10.1 Introduction

10.2 Specifications for Test Procedures and Acceptance Criteria for Drug Substances and Drug Products

10.3 Stability Testing for New Drug Substances and Drug Products

10.4 Initiation of Stability Studies

10.5 Photostability Testing of New Drug Substances and Drug Products

References

11 LC-MS for Pharmaceutical Analysis

11.1 Introduction

11.2 LC-MS Instrumentation

11.3 Examples of Qualitative and Quantitative Applications

11.4 Summary

References

12 Biorelevant Dissolution Testing

12.1 Background

12.2 Dissolution Apparatus

12.3 Media Used in Dissolution Testing

12.4

In Vitro

/

In Vivo

Correlation (IVIVC)

12.5 Summary

References

13 ICH Quality Guidelines

13.1 Introduction

13.2 Global Harmonization Forums

13.3 ICH Process

13.4 Impact of ICH Guidelines

13.5 Conclusion

Further Reading

14 Out of Specification/Atypical RESULT Investigation

14.1 Background

14.2 Identifying and Assessing OOS Test Results—Phase I: Laboratory Investigation

14.3 Expanded Investigating OOS/Atypical Test Results

14.4 Concluding the Investigation

14.5 Corrective and Preventive Action

Appendix i

Appendix ii Suggested OOS Investigation Flowchart

Appendix iii Example of initial assessment form

Appendix iv Example of reanalysis plan form

Appendix v Example of retest plan I form

Appendix vi Example of retest plan II form

Appendix vii Example of retest plan III form

Appendix Viii Example of final reporting for atypical/OOS result investigation form

References

Index

End User License Agreement

List of Tables

Chapter 01

Table 1.1 Regulatory sections of Part 211—current good manufacturing practice for finished pharmaceuticals

Table 1.2 Regulatory sections of Part 820—quality system regulation

Table 1.3 Regulatory sections of Part 600—biological products: general

Table 1.4 Regulatory sections of Part 601—biologic license application

Table 1.5 Regulatory sections of Part 610—general biological product standards

Table 1.6 Summary of application type and designated regulating center

Table 1.7 Compliance programs of CBER

Table 1.8 Compliance program in BIMO

Table 1.9 Compliance program in CDRH

Table 1.10 CDER compliance program

Chapter 02

Table 2.1 Content of a typical target product profile for an immediate-release tablet

Table 2.2 Typical target product profile: project plan and milestones for an immediate-release tablet

Table 2.3 Typical target product profile: clinical targets

Table 2.4 Typical target product profile: drug substance characteristics for an immediate-release tablet

Table 2.5 Typical target product profile: drug product characteristics of an immediate-release tablet

Table 2.6 Typical target product profile: drug substance specifications of an immediate-release tablet

Table 2.7 Typical target product profile: drug product specifications of an immediate-release tablet

Table 2.8 Typical target product profile: formulation composition of an immediate-release tablet

Table 2.9 Example of a checklist to select excipients for an immediate-release tablet

Table 2.10 Typical target product profile: manufacturing process of an immediate-release tablet

Chapter 03

Table3.1 Common polymers used in amorphous solid dispersions and their glass transition temperature

Chapter 04

Table 4.1 Classes of medical instruments in the United States, Europe, and Canada

Table 4.2 Summary of the main routes of administration that require a medical device to facilitate drug delivery

Table 4.3 Examples of inhalers for topical delivery to the lung

Table 4.4 Examples of inhalers for systemic delivery via the lung

Table 4.5 Examples of sl dosage forms

Table 4.6 ATMP types and key characteristics

a

Chapter 05

Table 5.1 ISO 10993 recommended testing and evaluation

Table 5.2 Summary of bone growth factor technologies commercially available and in development

Chapter 07

Table 7.1 Human islet transplantation studies currently recruiting

Chapter 08

Table 8.1 Cytotoxic T-cell (CTL) studies conducted by a commercial sponsor

Table 8.2 TCR gene therapy studies conducted by a commercial sponsor

Table 8.3 Car gene therapy studies conducted by an academic sponsor

Table 8.4 NK cell studies conducted by a commercial sponsor

Table 8.5 Antigen-presenting cell types and characteristics

Table 8.6 DC-based vaccine trials conducted by a commercial sponsor

Chapter 09

Table 9.1 Key chronological events of stem cell development

Table 9.2 Major ongoing randomized stem cell trials conducted by a commercial sponsor

Chapter 10

Table 10.1 Example specification of ABC DS

Table 10.2 Example specification of ABC capsule

Table 10.3 Example changes during development of XYZ capsule

Table 10.4 Test methods used in DSs

Table 10.5 Test methods used in DPs

Table 10.6 Example stability protocol template for ABC capsules

Table10.6.1

Example table summary of ABC capsule formulations

Table 10.6.2 Pull points for ABC capsules

Table10.6.3 Testing guidelines

Table 10.7 Usual storage conditions used in stability studies

Chapter 11

Table 11.1 LC-MS applications in different stages of drug development

Table 11.2 Common 1iquid chromatographic systems, ionization interfaces, and mass detectors for LC-MS and LC-MS/MS systems

Table 11.3 Performance of mass detectors

Chapter 12

Table 12.1 Apparatus typically used for special dosage forms

Table 12.2 Simple media used in dissolution testing

Table 12.3 SGF composition

Table 12.4 FaSSIF composition

Table 12.5 FeSSIF composition

Table 12.6 Simulated colonic fluid 1 (SCoF1)

Table 12.7 Simulated colonic fluid 2 (SCoF2)

Table 12.8 Properties of FaSSCoF and FeSSCoF

Table 12.9 Parameters used in IVIVC corresponding to the level

Chapter 13

Table 13.1 ICH Harmonization Activities

List of Illustrations

Chapter 02

Figure 2.1 High-level product development stages/phases, activities, and milestones.

Figure 2.2 Elements defining a pharmaceutical dosage form design.

Figure 2.3 Relationship between clinical, solid-state, and formulation development.

Figure 2.4 Example of a decision tree to develop drug substance specifications for an immediate-release tablet.

Figure 2.5 Process development steps for a typical immediate-release tablet.

Figure 2.6 Decision tree of selecting a manufacturing process for an immediately-release tablet.

Figure 2.7 Risk assessment and experimental design of a wet granulation process for a tablet formulation using a fishbone diagram.

Figure 2.8 Process optimization of MCC and lactose granulates by statistical design of experiment.

Chapter 03

Figure 3.1 Typical approach of formulation screening to improve the bioavailability of poorly soluble compounds.

Figure 3.2 An example of an uncertain path to improve bioavailability. Reproduced from Ref. 2, with permission of Patheon, Inc.

Figure 3.3 Biopharmaceutical classification system.

Figure 3.4 From dosing to systematic circulation—factors affecting bioavailability of poorly soluble compounds.

Figure 3.5 Summary of bioavailability enhancement technologies available in both development and commercial settings. Courtesy of Patheon Inc., with modification.

Figure 3.6 Particle engineering of drug candidate for formulation development.

Figure 3.7 An example of parallel technology screening program using a decision tree approach for human formulation. .

Figure 3.8 Excipient screening for solid dispersions using DSC—

in situ

formation and analysis of griseofulvin and PVP K 30 (10% (w/w)) solid dispersion. Courtesy of Patheon Inc.

Figure 3.9 Optical microscopy of (a) crystalline—PEG 3350 and (b) amorphous—SoluPlus® materials under cross-polarized light. Courtesy of Patheon Inc.

Figure 3.10 Decision tree for selection of technology and formulation to improve the bioavailability of poorly soluble drugs.

Chapter 04

Figure 4.1 Verification and validation of medical devices.

Figure 4.2 EpiPen® injector device. Reproduced with permission of Mylan Specialty L.P.

Figure 4.3 Turbuhaler® inhaler. Reproduction of Pulmicort® device provided courtesy of AstraZeneca Canada Inc.

Figure 4.4 Afrezza® inhaler (palm size). Reproduction of Afrezza device provided courtesy of MannKind Corporation.

Chapter 05

Figure 5.1 Systemic detection of a growth factor injection versus local retention of the growth factor by a carrier.

Figure 5.2 Local retention of a growth factor by different carriers that utilize both absorption (CaP granules, composite material, and collagen) and incorporation (both CaP cements).

Figure 5.3 An SEM image of a fibrous collagen scaffold with interconnected porosity.

Figure 5.4 Collagen (a), a natural polymer; biphasic calcium phosphate (b), a synthetic ceramic; and collagen and ceramic scaffold (c), a composite.

Chapter 06

Figure 6.1 Healthy volunteer insulin and glucose profiles. Reproduced from Ref. 2, with permission of McStroher, Creative Commons.

Figure 6.2 Glass syringes. © Bill Van Antwerp.

Figure 6.3 DCCT data. © Bill Van Antwerp.

Figure 6.4 Backpack pump. © Bill Van Antwerp.

Figure 6.5 Early insulin pump. Courtesy of Squidonius, Creative Commons.

Figure 6.6 Early insulin pump AutoSyringe. © Bill Van Antwerp.

Chapter 08

Figure 8.1 Structure of a typical CAR. 4-1BB or OX-40, costimulatory molecules belonging to the TNF/nerve growth factor super family of receptors; CD28, cluster of differentiation 28, provides costimulatory signal; CD3ζ, cluster of differentiation 3ζ, generates an activation signal in T lymphocytes; CD8, cluster of differentiation 8, a transmembrane glycoprotein that serves as a coreceptor for the TCR; C

H

, constant region of heavy chain; C

L

, constant region of light chain; scFv, single-chain variable fragment; V

H

, variable region of heavy chain; V

L

, variable region of light chain.

Chapter 10

Figure 10.1 Drug development cycle.

Chapter 11

Figure 11.1 Schematic of an ESI interface.

Figure 11.2 Schematic of an APCI interface.

Figure 11.3 Schematic diagram showing the different operation ranges for APCI and ESI in terms of relative polarity, mass range, and target analytes.

Figure 11.4 Schematic of the configuration of a quadrupole mass analyzer.

Figure 11.5 Schematic of the configuration of the electrodes in a 3D IT mass analyzer.

Figure 11.6 Schematic diagram showing the basic operation principle of TOF mass analyzer.

Figure 11.7 Scan mode for LC-MS/MS applications.

Figure 11.8 Mometasone furoate and its related impurities.

Figure 11.9 (a) MS spectrum of nonlabeled melamine. (b) MS spectrum of nonlabeled and labeled melamine. (c) Extracted ion chromatograms of the transitions of nonlabeled and labeled melamine and a calibration curve constructed based on the area ratio of ion nonlabeled and labeled melamine ion fragments.

Figure 11.10 Work for shotgun proteomics.

Figure 11.11 Chemical structure of the iTRAQ reagents and the stable isotope combinations.

Figure 11.12 Workflow of an iTRAQ experiment for protein quantitation.

Chapter 12

Figure 12.1 Factors that might impact drug dissolution. Reproduced from Ref. 7

Figure 12.2 Apparatus 1 and 2 dissolution test.

Figure 12.3 Franz cells as described in

Pharmacopeial Forum

. Reproduced from

Pharmacopeial Forum

, May-June 2009, with permission of the US Pharmocopeial Convention

Figure 12.4 Comparison of the solubility of montelukast (a) and glyburide (b) between high and low purity grades of taurocholate and lecithin.

Figure 12.5 (a) pH, surface tension, protein content, and total carbohydrate concentration of FaSSCoF and FeSSCoF compared to human colonic fluids. (b) Osmolarity, total bile, long-chain fatty acids, phosphatidylcholine, and cholesterol of FaSSCoF and FeSSCoF compared to human colonic fluids. Reproduced from Refs. 41 and 50.

Figure 12.6 A schematic of a PBPK model. Adopted simulation plus workshop. Reproduced from Ref. 68, with permission of Simulations Plus, Inc.

Figure 12.7 Biopharmaceutical parameters used to assess IVIVCs. If dissolution is faster than absorption, then the process is permeability controlled. If dissolution controls drug absorption, the dissolution testing might be a surrogate for

in vivo

dissolution. Reproduced from Ref. 7.

Figure 12.8 Dissolution specifications for Class I/III (a) and dissolution specifications for Class II/IV bioequivalence (BE) is expected in case (a) if a minimum required dissolution is achieved, in case (b) a minimum and maximum dissolution is required for BE.

Figure 12.9 Level B correlation between the

in vitro

MDT and

in vivo

MRT. Reproduced from Ref. 80, with permission of Springer Science and Business Media.

Figure 12.10 Left: mean

in vitro

dissolution data (a) and

in vivo

plasma concentration data (b) for metformin. Right: level C IVIVC for metformin. Mean observed AUC as a function of

in vitro

dissolution at 0.5, 2, and 4 h (a). AUC plotted versus the

in vitro

MDT (b). Reproduced from Ref. 62, with permission of Wiley-Liss, Inc. and the American Pharmaceutical Association.

Figure 12.11 pH-dependent calculated Do for 80  mg gliclazide dose. Dotted lines represent the critical Do for GLK (conservative upper limit of Do = 1 and the calculated value of Do = 14.5).Reproduced from Ref. 82, with permission of Springer Science and Business Media

Figure 12.12 Dissolution of montelukast sodium in different dissolution media using USP apparatus 2 and a flow-through cell. The profiles were used in GastroPlus to simulate the

in vivo

performance. Reproduced from Ref. 45, with permission of Elsevier.

Guide

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Therapeutic Delivery Solutions

Edited by

Chung Chow Chan

CCC Consulting

Mississauga, Ontario, Canada

Kwok Chow

Covar, Inc.

Mississauga, Ontario, Canada

Bill McKay

Medtronic, Inc.

Memphis, TN, USA

Michelle Fung

Gordon and Leslie Diamond Health Care Centre

University of British Columbia

Vancouver, British Columbia, Canada

Copyright © 2014 by John Wiley & Sons, Inc. All rights reserved

Published by John Wiley & Sons, Inc., Hoboken, New JerseyPublished simultaneously in Canada

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Library of Congress Cataloging-in-Publication Data:

Therapeutic delivery solutions / edited by Chung Chow Chan, Kwok Chow, Bill McKay, Michelle Fung.        p. ; cm.    Includes index.

    ISBN 978-1-118-11126-0 (cloth)I. Chan, Chung Chow, editor. II. Chow, Kwok, 1956– editor. III. McKay, Bill, 1956– editor. IV. Fung, Michelle, editor.[DNLM: 1. Drug Delivery Systems–United States. 2. Cell- and Tissue-Based Therapy–methods–United States. QV 785]     RS199.5     615′.6–dc23

2014007293

Preface

The technologies for the administration of therapeutic agents have been traditionally led by the pharmaceutical industry that develops drug molecules (both small and large molecules) in various dosage forms. The medical device industry has also evolved to apply its technologies to deliver drugs to various target sites.

Cellular therapy is now rapidly emerging as a new therapeutic solution platform, analogous to dosage form design and device development, in the last few decades. Under the Executive Order 13505 of March 9, 2009, in the United States, President Obama’s Administration is committed to supporting and conducting ethically responsible, scientifically worthy human stem cell research, including human embryonic stem cell research. “National Institutes of Health Guidelines for Human Stem Cell Research” (Guidelines), effective July 7, 2009, applies to research using human embryonic stem cells and certain uses of human-induced pluripotent stem cells that have the potential to improve our understanding of human biology and aid in the discovery of new ways to prevent and treat illness. Researches in cellular therapy, for example, stem cells, have had very promising results as therapeutic solutions to diseased states and organ transplants.

This textbook provides a convergent link between traditional dosage form design, medical device development, and cellular therapeutics. It attempts to bring these three platforms of therapeutic delivery solution development together in one place to show the potential idiosyncrasies and common and dissimilar challenges that each platform faces to provide the best therapeutic delivery solution to the patient. Contemporary scientific and medical information as well as the newly emerging regulatory scientific information are discussed. This textbook will provide development scientists and medical professionals more options to develop a therapeutic agent to its fullest potential and create better and more creative therapeutic solutions.

The content of the book is grouped into five sections. Section 1 (consisting of Chapter 1) introduces the requirements and issues encountered in regulatory submissions in the pharmaceutical, cellular/gene products, and medical device industries. Section 2 (consisting of Chapters 2 and 3) explains in detail the traditional pharmaceutical drug therapy development. Section 3 (consisting of Chapters 4–6) provides an overview, current trends, and strategies of special medical device development. Section 4 (consisting of Chapters 7–9) introduces the reader to the latest advances and innovations in cellular and stem cell therapeutic delivery. Section 5 (consisting of Chapters 10–14) provides information on the analytical support needed for the research and development in Sections 2–4.

Chapter 1 provides an overview of the current regulatory requirements for the development of the three platforms of therapeutic solution and new FDA initiatives to ensure that innovative products reach the patients who need them and when they need them.

An overview of the approach and strategies for development of immediate release tablets after a drug candidate is selected is provided in Chapter 2. Chapter 3 discusses the strategies (with examples) for the development of low aqueous solubility drug products.

Chapter 4 starts with an overview, key trends, and drivers for drug delivery medical devices. Chapter 5 focuses on the local growth factor delivery to address metabolic bone disorders. “From glass syringes to feedback-controlled patch pumps”, Chapter 6 discusses the amazing accomplishment for the pharmaceutical and medical device industries with the insulin pump to continuously deliver precise amounts of insulin 24 h a day.

Cell-based biologic therapies have a long history. Simple blood transfusions and tissue transplants are commonly utilized in medical practice. Chapter 7 reviews the history of islet transplantation, procedural issues, current outcomes, and future directions. Chapter 8 provides an overview of the latest developments of cell-based biologic therapies and discusses the future outlook for these novel treatment modalities, for example, cancer, infection, and autoimmune disorders. Chapter 9 reviews the history of stem cell research and development, sources of various stem cells (e.g., neonatal, adult, reprogrammed), technical and regulatory issues of stem cell therapy, and the prospect of industrialization of stem cell technology into future medical therapy.

Chapters 10 to 14 provide the analytical support needed in the development of the three platforms of therapeutic solution delivery. Chapter 10 summarizes the specifications setting and stability studies requirements for development work. Chapter 11 shows how LC–MS techniques have been used in all stages of the drug development process including discovery, preclinical, clinical, and manufacturing. Chapter 12 discusses the importance of biorelevant methods and how to achieve them. Chapter 13 provides information and importance of ICH guidelines for development and global harmonization. In the development of therapeutic solution, there will be situations when out of specification (OOS) or aberrant data are obtained. Chapter 14 looks at how the use of sound scientific judgment and good documentation can lead to a successful OOS/atypical result investigation in a case study according to current guidance.

CCC ConsultingCovar Inc.Medtronic Inc.University of British Columbia

Chung Chow Chan, PhDKwok Chow, PhDBill McKay, MEMichelle Fung, MD

Contributors

May Almukainzi, PhD, Faculty of Pharmacy and Pharmaceutical Sciences, University of Alberta, Edmonton, Alberta, Canada; Faculty of Pharmacy, Princess Nora Bint AbdulRahman University, Riyadh, Saudi Arabia

Ziliang Ao, MD, MSc, Ike Barber Human Islet Transplant Laboratory Surgery, Faculty of Medicine, University of British Columbia, Vancouver, British Columbia, Canada

James Blakemore, PhD, Cambridge Consultants Ltd., Science Park, Cambridge, UK

Nádia Araci Bou-Chacra, PhD, Faculty of Pharmaceutical Sciences, University of São Paulo, São Paulo, Brazil

Debra L. Bowen, MD, FACAAI, Pharma Science Consulting, Inc., Milford, NH, USA

Chung Chow Chan, PhD, CCC Consulting, Mississauga, Ontario, Canada

Kwok Chow, PhD, Covar, Inc., Mississauga, Ontario, Canada

Jared Diegmueller, MS, Medtronic Spinal and Biologics, Memphis, TN, USA

Man C. Fung, MD, MBA, MHCM, FACP, Janssen Pharmaceutical R&D (JNJ), Janssen Oncology, Raritan, NJ, USA

Michelle Fung, BASc, MD, MHSc, Department of Medicine, Faculty of Medicine, University of British Columbia,

Vancouver, British Columbia, Canada

Sultan Ghani, BSc, BPharm, MS, Quality Management & Regulatory Affairs (QMRA), Getz Pharma Pvt. Limited, Karachi, Pakistan

Stephen G.F. Ho, MD, FRCPC, Department of Radiology, Faculty of Medicine, University of British Columbia, Vancouver, British Columbia, Canada

Klaudyne Hong, PhD, Temasek Bioscience Partners, NY, USA

James D. Johnson, PhD, Department of Surgery, Faculty of Medicine, University of British Columbia, Vancouver, British Columbia, Canada

Paul Keown, MD, Department of Medicine, Faculty of Medicine, University of British Columbia, Vancouver, British Columbia, Canada

Herman Lam, PhD, Wild Crane Horizon, Scarborough, Ontario, Canada

Raimar Löbenberg, PhD, Faculty of Pharmacy and Pharmaceutical Sciences, University of Alberta, Edmonton, Alberta, Canada

Bill McKay, ME, Medtronic Spinal and Biologics, Memphis, TN, USA

Mark Meloche, MD, Department of Surgery, Faculty of Medicine, University of British Columbia, Vancouver, British Columbia, Canada

Graydon Meneilly, MD, Department of Medicine, Faculty of Medicine, University of British Columbia, Vancouver, British Columbia, Canada

Breay W. Paty, MD, Department of Medicine, Faculty of Medicine, University of British Columbia,

Vancouver, British Columbia, Canada

Steven Peckham, PhD, Medtronic Spinal and Biologics, Memphis, TN, USA

R. Jean Shapiro, MD, Department of Medicine, Faculty of Medicine, University of British Columbia, Vancouver, British Columbia, Canada

Iain Simpson, PhD, Cambridge Consultants Ltd., Science Park, Cambridge, UK

David Thompson, MD, Department of Medicine, Faculty of Medicine, University of British Columbia, Vancouver, British Columbia, Canada

Yu-Hong Tse, PhD, YH & MJ Consulting, Brampton, Ontario, Canada

Bill Van Antwerp, Zyomed Corp., Valencia, CA, USA

Bruce Vechere, PhD, Pathology & Laboratory Medicine and Surgery, Faculty of Medicine, University of British Columbia, Vancouver, British Columbia, Canada

Roderick B. Walker, Faculty of Pharmacy, Rhodes University, Grahamstown, South Africa

Garth Warnock, MD, MSc, Department of Surgery, Faculty of Medicine, University of British Columbia, Vancouver, British Columbia, Canada

Acknowledgment

We would like to thank all the authors and contributors who are leading scientists and physicians in the respective areas for their contributions to the chapters in this book.

Section 1Requirements and Issues encountered in Regulatory Submissions in the Pharmaceutical, Cell Therapy and Medical Device Industries

1Challenges to Quality and Regulatory Requirement in the United States—Drugs, Medical Device, and Cell Therapy

Chung Chow Chan, Sultan Ghani, Iain Simpson and James Blakemore

1.1 Overview of Regulatory Requirements for Pharmaceutical, Medical Device, and Cell Therapies

The technologies for the administration of therapeutic agents had been traditionally led by the pharmaceutical industry, which develops small drug molecules into various dosage forms. These developments have been followed by large-molecule pharmaceutical development (proteins, etc.), device development, and the new emerging cellular therapy. Recent breakthroughs in science and technology (ranging from sequencing of the human genome to advances in the application of nanotechnology to new medical products) are transforming the ability to treat diseases and bring with it new challenges in regulatory approval.