Therapeutic Protein Drug Products

Therapeutic protein drug products provides a comprehensive overview of therapeutic protein drug products, with an emphasis on formulation beginning in the laboratory, followed by manufacturing and administration in the clinic. A list of many commercial therapeutic drug products are described and include the product name, dosages, active concentration, buffer, excipients, Ph, container type and route of administration. The laboratory formulation sections focus on the most common buffers, excipients, and Ph ranges that are commonly tested in addition to systematic approaches. A brief section on biophysical and analytical analysis is also provided. Properties of therapeutic protein formulations are described and include opalescence, phase separation, color, and subvisible particles. An emphasis is placed on material and process testing to ensure success during manufacturing. The drug product manufacturing process, which includes the process of compounding to filling, is also covered. Methods of delivery in the clinic are addressed, as well as delivery strategies. Finally, a perspective on the regulatory requirements for therapeutic protein formulations is discussed.

• Provides a list and description of commercially available therapeutic drug products and their formulations
• A comprehensive and practical overview of protein formulation in the laboratory, manufacturing, and the clinic

• Discusses recent topics including high protein concentration, phase separation, opalescence, and subvisible particles

  Autorentext

  Dr Brian K. Meyer is a Research Fellow in Bioprocess Research and Development, Merck Research Laboratories (MRL). Dr Meyer and his team are responsible for formulating therapeutic proteins in pre-clinical development. Prior to joining MRL, Dr Meyer was a Process Scientist in Vaccine Technology and Engineering, Merck Manufacturing Division. He has a Ph.D. in Biochemistry, Microbiology, and Molecular Biology from The Pennsylvania State University and a B.S.E. in Biomedical Engineering from Tulane University.

  Inhalt

  List of figures and tables

  Preface

  About the authors

  Chapter 1: Commercial therapeutic protein drug products

  Abstract

  1.1 Introduction

  1.2 Lyophilized formulations

  1.3 Liquid formulations

  1.4 Protein formulations for radiologic and diagnostic use

  1.5 Summary

  Chapter 2: A formulation method to improve the physical stability of macromolecular-based drug products

  Abstract

  2.1 Introduction

  2.2 Common techniques used for the construction of EPDs

  2.3 The peptide drug pramlintide

  2.4 Monoclonal antibodies at low and high concentration

  2.5 Static vs. dynamic EPDs: a case study using a humanized immunoglobulin (IgG1)

  2.6 Conclusion and future studies

  Chapter 3: Properties of protein formulations

  Abstract

  3.1 Introduction

  3.2 Opalescence

  3.3 Phase separation

  3.4 Color

  3.5 Subvisible particles

  Chapter 4: Material and process compatibility testing

  Abstract

  4.1 Introduction

  4.2 Material compatibility

  4.3 Process compatibility testing

  4.4 Antimicrobial preservative compatibility testing

  Chapter 5: Compounding and filling: drug substance to drug product

  Abstract

  5.1 Introduction

  5.2 Aseptic processing

  5.3 Bulk drug substance

  5.4 Compounding of drug product

  5.5 Filling the drug product

  Chapter 6: Administration in the clinic

  Abstract

  6.1 Introduction and background

  6.2 Diluents

  6.3 Components

  6.4 Construction materials

  6.5 Clinical dosing strategy: fixed volume versus fixed concentration

  6.6 Representative admixture concentration levels

  6.7 Exposure temperature and time

  6.8 Option of using syringes

  6.9 Analytical tests and acceptance criteria

  6.10 Sample preparation considerations

  6.11 Role of probe studies

  6.12 Bag overfill volume

  6.13 Pharmacy instructions

  6.14 Conclusions

  Chapter 7: Regulatory guidelines for the development of a biotechnology drug product

  Abstract

  7.1 Introduction

  7.2 ICH overview

  7.3 Common Technical Document (CTD)

  7.4 Drug product dossier

  7.5 Regulatory considerations through the biotechnology product lifecycle

  7.6 Conclusions

  Appendix

  Recommended reading

  Index