Novel Therapeutics from Modern Biotechnology

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.