© 2018

Challenges in Protein Product Development

  • Nicholas W. Warne
  • Hanns-Christian Mahler


  • Discusses the challenges faced in biotechnology dosage form development

  • Provides practical and applied guidance in many areas including stability, microbiology and manufacturing, as well as case studies in life-cycle management

  • Includes comprehensive information on the use of polysorbate exipients in formulation


Part of the AAPS Advances in the Pharmaceutical Sciences Series book series (AAPS, volume 38)

Table of contents

  1. Front Matter
    Pages i-xvi
  2. Formulation Development of Biologics

    1. Front Matter
      Pages 1-1
    2. Daniel Weinbuch, Andrea Hawe, Wim Jiskoot, Wolfgang Friess
      Pages 3-22
  3. Challenges with Excipients

    1. Front Matter
      Pages 23-23
    2. Kishore S. K. Ravuri
      Pages 25-62
  4. High Concentration Proteins

    1. Front Matter
      Pages 97-97
    2. Wei Wang, Arun Alphonse Ignatius, Satoshi Ohtake, Teng-Chieh Yang
      Pages 99-123
    3. Hanns-Christian Mahler, Anja Matter
      Pages 125-137
    4. Andrea Allmendinger, Stefan Fischer, Robert Mueller
      Pages 139-161
    5. Deirdre Murphy Piedmonte, Jian Hua Gu, Stephen R. Brych, Monica M. Goss
      Pages 163-187
  5. Container-Closure Systems

    1. Front Matter
      Pages 189-189
    2. Roman Mathaes, Alexander Streubel
      Pages 191-202
    3. Mariana N. Dimitrova, Jared S. Bee, Ling Lu, Jason E. Fernandez
      Pages 203-224
    4. Dirk Gläser, Jürg Liniger, Daniel Peter
      Pages 235-256
    5. Holger Roehl, Philippe Lam, Dominique Ditter
      Pages 291-304
    6. Holger Roehl, Philippe Lam, Dominique Ditter
      Pages 305-309
  6. Processing Considerations

    1. Front Matter
      Pages 311-311

About this book


In this volume, the authors discuss the many significant challenges currently faced in biotechnology dosage form development, providing guidance, shared experience and thoughtful reflection on how best to address these potential concerns. As the field of therapeutic recombinant therapeutic proteins enters its fourth decade and the market for biopharmaceuticals becomes increasingly competitive, companies are increasingly dedicating resources to develop innovative biopharmaceuticals to address unmet medical needs. Often, the pharmaceutical development scientist is encountering challenging pharmaceutical properties of a given protein or by the demands placed on the product by stability, manufacturing and preclinical or clinical expectations, as well as the evolving regulatory expectations and landscape. Further, there have been new findings that require close assessment, as for example those related to excipient quality, processing, viscosity and device compatibility and administration, solubility and opalescence and container-closure selection. The literature varies widely in its discussion of these critical elements and consensus does not exist. This topic is receiving a great deal of attention within the biotechnology industry as well as with academic researchers and regulatory agencies globally. Therefore, this book is of interest for business leaders, researchers, formulation and process development scientists, analytical scientists, QA and QC officers, regulatory staff, manufacturing leaders and regulators active in the pharmaceutical and biotech industry, and expert reviewers in regulatory agencies.


ADCs Mabs biologics formulation lyophilization therapeutic proteins HC Protein formulations container closure formulations parenteral products bulk protein solution lyophilization fusion proteins biotherapeutic dosage forms novel constructs

Editors and affiliations

  • Nicholas W. Warne
    • 1
  • Hanns-Christian Mahler
    • 2
  1. 1.BioTherapeutics Research and Development Pharmaceutics Research and DevelopmentPfizer Inc.AndoverUSA
  2. 2.Lonza AGDrug Product ServicesBaselSwitzerland

About the editors

Nicholas W. Warne is currently Senior Director of Formulations and Drug Product Process Development at Pfizer.  Dr. Warne has 28 years of industrial experience focusing on biologics formulation development, dosage form design and manufacturing process development.  He and his team have been fortunate to have contributed to the licensure of 10 biologics including clotting factors, growth proteins, mabs, vaccines and ADCs.  Dr. Warne holds numerous protein formulation patents and, with his group, has made over 100 presentations at national meetings and in journals.  Prior to his position at Pfizer, Dr. Warne had positions of increasing responsibility at Wyeth and Genetics Institute, and has been based in Andover, Massachusetts.

Dr. Warne received his PhD in Chemistry from Purdue University under the guidance of Professor Michael Laskowski Jr. He received his BS in Biochemistry, with Distinction in Research, from the University of Rochester. 

Hanns-Christian Mahler. Since September 2015, Dr. Mahler is leading the Drug Product services organization at Lonza AG, a leading service provider for the Pharma and Biotech industry. Prior this position, he led the department Pharmaceutical Development & Supplies, Biologics EU at Roche, Basel, Switzerland from 2010 to 2015 and as Head of Formulation R&D Biologics, Roche, Basel, from 2005 to 2010. From 2000-2005, Dr. Mahler was working at Merck KGaA, Darmstadt, Germany as Principal Formulation Scientist, Lab Manager for Protein Formulation Development and Clinical Trial Manufacturing and CMC Team leader for Erbitux during its submission and launch phase.

Dr. Mahler studied Pharmacy at the University of Mainz, Germany, holds in Ph.D. in Toxicology from the Institute of Pharmacy, University of Mainz and Pharmacist specialization degrees in Toxicology & Ecology and Pharmaceutical Technology. He was further trained in Economy and Marketing. Dr. Mahler obtained his venia legendi (german Habilitation) from the University of Frankfurt/Germany in 2010 and is adjunct faculty and lecturer at the universities of Frankfurt (Germany), and Basel (Switzerland). He was elected an AAPS Fellow in November 2013, nominated extraordinary Professor for Pharmaceutical Technology in November 2015 and received the PDA Distinguished Service Award in 2018.

Bibliographic information

  • Book Title Challenges in Protein Product Development
  • Editors Nicholas W. Warne
    Hanns-Christian Mahler
  • Series Title AAPS Advances in the Pharmaceutical Sciences Series
  • Series Abbreviated Title AAPS Adv. Pharmaceutical Sciences
  • DOI
  • Copyright Information American Association of Pharmaceutical Scientists 2018
  • Publisher Name Springer, Cham
  • eBook Packages Biomedical and Life Sciences Biomedical and Life Sciences (R0)
  • Hardcover ISBN 978-3-319-90601-0
  • Softcover ISBN 978-3-030-08052-5
  • eBook ISBN 978-3-319-90603-4
  • Series ISSN 2210-7371
  • Series E-ISSN 2210-738X
  • Edition Number 1
  • Number of Pages XVI, 599
  • Number of Illustrations 55 b/w illustrations, 75 illustrations in colour
  • Topics Pharmaceutical Sciences/Technology
  • Buy this book on publisher's site
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