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Introduction into Formulation Development of Biologics

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Challenges in Protein Product Development

Part of the book series: AAPS Advances in the Pharmaceutical Sciences 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.

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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

  1. Formulation and Process Development Strategies for Manufacturing Biopharmaceuticals. F. Jameel, S. Hershenson (Editors), 2010. Hoboken, NJ, USA: John Wiley & Sons. ISBN 978-0-470-111812-2.

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  3. 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.

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Author information

Authors and Affiliations

  1. Department of Pharmacy—Pharmaceutical Technology and Biopharmaceutics, Ludwig-Maximilians-Universität München, Butenandtstr. 5-13, 81377, Munich, Germany

    Wolfgang Friess

  2. Coriolis Pharma Research GmbH, Fraunhoferstr. 18B, 82152, Martinsried, Germany

    Daniel Weinbuch & Andrea Hawe

  3. Division of BioTherapeutics, Leiden Academic Centre for Drug Research, Leiden University, Einsteinweg 55, 2333 CC, Leiden, The Netherlands

    Daniel Weinbuch & Wim Jiskoot

Authors
  1. Daniel Weinbuch
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  2. Andrea Hawe
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  3. Wim Jiskoot
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  4. Wolfgang Friess
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Corresponding author

Correspondence to Wolfgang Friess .

Editor information

Editors and Affiliations

  1. BioTherapeutics Research and Development Pharmaceutics Research and Development, Pfizer Inc., Andover, Massachusetts, USA

    Nicholas W. Warne

  2. Lonza AG, Drug Product Services, Basel, Basel Stadt, Switzerland

    Hanns-Christian Mahler

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© 2018 American Association of Pharmaceutical Scientists

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Weinbuch, D., Hawe, A., Jiskoot, W., Friess, W. (2018). Introduction into Formulation Development of Biologics. In: Warne, N., Mahler, HC. (eds) Challenges in Protein Product Development. AAPS Advances in the Pharmaceutical Sciences Series, vol 38. Springer, Cham. https://doi.org/10.1007/978-3-319-90603-4_1

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