Formulation and Process Development for Lyophilized Biological Reference Materials

  • Paul MatejtschukEmail author
  • Kiran Malik
  • Chinwe Duru
Part of the Methods in Pharmacology and Toxicology book series (MIPT)


Biologicals can often be inherently unstable in the liquid state and require lyophilization to ensure long-term stability. We describe our approach to the lyophilization of a wide range of biological reference materials, many prepared as part of our work on behalf of the WHO, to develop freeze-dried reference materials to assign biological activity. These can cover a wide range of materials, often purified proteins and sera but also including nucleic acids and viruses. Recent trends in optimizing our approach are presented; the importance of noninvasive monitoring is illustrated and the challenges of formulation design and cycle optimization are discussed.

Key words

Biological reference materials Formulation Cycle optimization Design of experiments Nucleic acids Viruses 



We thank our many colleagues at NIBSC with whom development studies have been undertaken and those in the Standards Processing Division with whom we cooperate to deliver large-scale batches of lyophilized material. We also thank academic collaborators, especially Professor Paul Dalby, UCL and former students Drs. Mathew Robinson and Yitzchak Grant.


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Copyright information

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

Authors and Affiliations

  1. 1.National Institute for Biological Standards & Control (NIBSC)Potters BarUK
  2. 2.Standardisation ScienceNational Institute for Biological Standards & Control (NIBSC)Potters BarUK

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