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Lyophilization of High-Concentration Protein Formulations

  • Patrick GaridelEmail author
  • Ingo Presser
Protocol
Part of the Methods in Pharmacology and Toxicology book series (MIPT)

Abstract

High-concentration protein formulations are in the focus of current pharmaceutical development because the required therapeutic doses of biologics, especially monoclonal antibodies, are extremely high, ranging between 5 and 750 mg per patient. Considering applications via the sub-cutaneous route, protein concentrations much above 300 mg/mL are often requested. At present, commercialized high-concentration biologics, with protein concentrations between 150 and 200 mg/mL, are launched as lyophilized (freeze-dried) products, while liquid protein formulations are available with concentrations around 100 mg/mL.

The current chapter will address specific topics linked to high-concentration lyophilized protein formulations. The term “high-concentration protein formulation” (HCPF) is often used, but hardly ever defined. We have therefore asked, how highly concentrated can a protein formulation become? We consider this question, particularly for monoclonal antibody drugs, along with the rationale for developing HCPF and the issues encountered during formulation.

Lyophilization is the technique of choice for stabilizing labile molecules. However, for the development of high-concentration, freeze-dried protein formulations (HC-FDPFs), new challenges appear, such as extremely prolonged reconstitution times or even stability issues. Therefore, new technologies such as controlled nucleation are introduced and presented as one option for reducing these unfavorable reconstitution times.

Key words

High-concentration Protein Lyophilization Freeze-drying Controlled nucleation Pharmaceutical development Monoclonal antibody Formulation Packaging characteristics Solubility Colloidal properties 

Notes

Acknowledgments

The authors thank the following people for supporting the current study: Alexander Kuhn, Torsten Schultz-Fademrecht, Andreas Langer, Ortrud Betz, Regina Ziegler, Heidrun Schott, Sven Bahrenburg, Robert Mader, Douglas McCormick and Raimund Geidobler.

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Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2019

Authors and Affiliations

  1. 1.Corporate Division Biopharmaceuticals, Process Science, Protein ScienceBoehringer Ingelheim Pharma GmbH & Co. KGBiberach an der RissGermany

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