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Introduction into Formulation Development of Biologics

  • Daniel Weinbuch
  • Andrea Hawe
  • Wim Jiskoot
  • Wolfgang Friess
Chapter
Part of the AAPS Advances in the Pharmaceutical Sciences Series book series (AAPS, volume 38)

Abstract

Formulation development is an essential part of every biopharmaceutical development program and important for the therapeutic and commercial success of a protein drug product by assuring the quality, safety, and efficacy. The multiple phases of formulation development interact with other product development exercises as early as discovery research all the way until and beyond market approval. Every drug product demands a tailor-made formulation, due to the complexity of different degradation pathways potentially affecting product stability, the specific characteristics of the individual drug molecule, special patient needs, and even marketing considerations. Formulation development can be approached using various strategies, based on a rational design, relying on scientific knowledge in low or medium throughput, or high-throughput formulation screening of hundreds or even thousands of conditions employing miniaturized analytical methods. In this chapter, an introduction to the field of protein formulation development is given, the literature on current protein formulation development strategies is reviewed, and current challenges are summarized.

Keywords

Protein stability Stability testing Preformulation High throughput screening Excipients Development strategy 

List of Abbreviations

AF4

Asymmetrical flow field-flow fractionation

API

Active pharmaceutical ingredient

AUC

Analytical ultracentrifugation

CTA

Clinical trial authorization

DLS

Dynamic light scattering

DNA

Deoxyribonucleic acid

DOE

Design of experiment

DP

Drug product

DS

Drug substance

DSC

Differential scanning calorimetry

DSF

Differential scanning fluorimetry

FTIR

Fourier-transform infrared

Glu

Glutamic acid

GMP

Good manufacturing practice

h

Hour(s)

H2O2

Hydrogen peroxide

His

Histidine

HPLC

High-performance liquid chromatography

HTF

High-throughput formulation

ICH

International conference on harmonization

LA

License application

LC-MS

Liquid chromatography-coupled mass spectrometry

mg/ml

Milligram per milliliter

mM

Millimolar

μm

Micrometer

nm

Nanometer

pH

Potential of hydrogen

pI

Isoelectric point

pKa

Acid dissociation constant

QC

Quality control

RH

Relative humidity

RNA

Ribonucleic acid

rpm

Rounds per minute

SEC

Size exclusion chromatography

SLS

Static light scattering

Tg’

Glass transition temperature

UPLC

Ultrahigh-performance liquid chromatography

USP

United States Pharmacopeia

UV

Ultraviolet

°C

Degrees Celsius

%

Percent

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Further Reading

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    Rationale Design of stable protein formulations-theory and practice. J.F. Carpenter, M.C. Manning (Editors), 2002. New York, NY, USA. Kluwer Academic/Plenum. ISBN 978-1-4615-0557-0.Google Scholar
  3. 49.
    Development and Manufacture of Protein Pharmaceuticals. S.L. Nail, M.J. Akers (Editors), 2002. New York, NY, USA. Kluwer Academic/Plenum. ISBN 978-1-4615-0549-5.Google Scholar

Copyright information

© American Association of Pharmaceutical Scientists 2018

Authors and Affiliations

  • Daniel Weinbuch
    • 2
    • 3
  • Andrea Hawe
    • 2
  • Wim Jiskoot
    • 3
  • Wolfgang Friess
    • 1
  1. 1.Department of Pharmacy—Pharmaceutical Technology and BiopharmaceuticsLudwig-Maximilians-Universität MünchenMunichGermany
  2. 2.Coriolis Pharma Research GmbHMartinsriedGermany
  3. 3.Division of BioTherapeutics, Leiden Academic Centre for Drug ResearchLeiden UniversityLeidenThe Netherlands

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