A cover story of Business Week Magazine in January 1984 stated "Biotech Comes of Age". In February 1986, Venture Magazine had a cover article entitled "The Biotech Revolution is Here". This article went on to say "New Genetic Technologies Will Transform Our Lives". These announcements were made many years after the first biotechnology companies, such as Genentech, Cetus, Amgen and Biogen, were formed-to commercialize the "New Biology". . At the time of writing this book, there are over 1300 biotech companies developing new technologies or identifying potential biotech drugs. Most of these companies were started in the height of the "high-technology hype", although companies are still forming as the technology advances. A more recent survey showed only a relatively small number of Food and Drug Administration (FDA) approvals among over several hundred biotech nology products now in clinical trial. One could ask why it has taken so long to produce biotechnology products. Part of the reason is that each new class of biotech products brings with it a set of problems that need to be solved before they enter clinical trials. These problems are often unique to biotechnology products, such as peptides, proteins, monoclonal antibodies, nucleic acids and cellular therapies.

1 Overview of Regulatory Expectations for Introducing Novel Therapies into Clinical Trials

A. Introduction
B. Roles of Regulatory Scientists
C. Product Development and Availability
D. Data Requirements
E. Manufacturing
F. Preclinical Safety Testing
G. Case-By-Case Approach
H. Testing Goals
I. Study Design
J. Defining Exposure
K. Product-Specific Concerns
L. Accessibility of Preclinical Safety Data
M. Clinical Studies
N. Summary
References
2 Preparation of Clinical Trial Supplies of Biopharmaceuticals
A. Introduction
B. Preclinical Studies
C. Clinical Supplies
D. Purification of rDNA-Derived Anti-RSV MAb
E. Product Quality Issues
F. Process Design and Validation
G. Process Economics and the Future of Chromatography
H. Conclusions
References
3 Proteins as Drugs: Analysis, Formulation and Delivery
A. Introduction
B. The Analysis of Protein Pharmaceuticals
C. Formulation
D. Delivery
References
4 Strategies for Dealing With the Immunogenicity of Therapeutic Proteins
A. Introduction
B. Case Histories of Protein Therapeutic Development
C. Strategies Under Development for Increasing the Therapeutic Value of Proteins and Peptides
D. Choosing the Proper Strategy for a Protein Therapeutic
E. The Future of Protein Therapeutics
References
5 Targeted Toxin Hybrid Proteins
A. Introduction
B. Preclinical Development of Anti-Tac(Fv) Toxins
C. Preclinical Development of Inerleukin 6-PE4E
D. Summary
References
6 SB 209763: A Humanized Monoclonal Antibody for the Prophylaxis and Treatment of Respiratory Syncytial Virus Infection
A. Introduction
B. Early Challenges in the Development of SB 209763
C. Preclinical Evaluation Prior to Testing in Humans
D. Challenges for the Early Clinical Development of SB 209763
E. Conclusion
References
7 Preclinical Development of Antisense Therapeutics
A. Introduction
B. Pharmacology of Antisense Oligodeoxynucleotides
C. Pharmacokinetics and Toxicity of Oligodeoxynucleotide Therapeutics
D. Chemistry, Manufacture and Control of Phosphorothioate Oligodeoxynucleotide Drugs
E. Formulation and Drug Delivery of Oligodeoxynucleotides
F. Summary
References
8 Formulation and Delivery of Nucleic Acids
A. Introduction
B. Formulation of DNA
C. Delivery to Target Cells
D. Cell Entry
E. Endosomal Release
F. Nuclear Localization
G. Gene Expression
References
9 Safe, Efficient Production of Retroviral Vectors
A. Introduction
B. Vectors
C. Production of Retroviral Vectors
D. Downstream Processing
E. GMP Production of Retroviral Vectors
F. In-Process Assays
G. Quality Control
H. Safety
I. Summary and Conclusions
References
10 Clinical Systems for the Production of Cells and Tissues for Human Therapy
A. Introduction
B. Cell Therapy and Tissue Engineering
C. Critical Requirements for Ex Vivo Cell Production
D. Cell-Culture Devices and Procedures
E. Applications for On-Site Delivery of Therapeutic Cell Production
F. Summary
References.