Therapeutic Protein Drug Products

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

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

The pharmaceutical and biotechnology industries