Low pH, caprylate incubation as a second viral inactivation step in the manufacture of albumin: Parametric and validation studies

Anna Johnston, Eric Uren, David Johnstone, John Wu

Research output: Contribution to journalArticle

37 Citations (Scopus)

Abstract

Caprylate has long been used as a stabiliser for albumin solutions, as well as a precipitation agent for immunoglobulins, ceruloplasmin and more recently in removing contaminants during albumin purification. Its virucidal properties have been explored and it has been proposed that the non-ionised form of the caprylate acid disrupts the integrity of the lipid bilayer and membrane associated proteins of enveloped viruses. The studies reported here further explore the use of this fatty acid to inactivate lipid-enveloped viruses in albumin manufactured for therapeutic use. Caprylate concentrations considered above solubility limits were adopted. Acidic pH was used to maximise the percentage of non-ionised caprylate and elevated temperatures were used to enhance inactivation rates. Parameters were manipulated to determine the relationship between pH, temperature and caprylate: protein ratio. These studies demonstrated that elevated temperature and low pH were critical in achieving significant reduction in virus infectivity and that the rate and extent of inactivation was sensitive to changes in caprylate:protein ratio and to changes in pH. Final inactivation conditions of 10% w/v protein, 16 mM caprylate, pH 4.5 and 30°C were chosen to minimise protein dimerisation and to achieve greater than 4 log10inactivation of the most resistant virus tested, bovine viral diarrhoea virus. Validation studies using both model and relevant blood borne viruses demonstrated this to be a robust and effective viral inactivation step and is complementary to the commonly used pasteurisation viral inactivation step, thus providing an additional margin of safety to this valuable therapeutic blood product.

Original languageEnglish
Pages (from-to)213-221
Number of pages9
JournalBiologicals
Volume31
Issue number3
DOIs
Publication statusPublished - Jan 1 2003
Externally publishedYes

Keywords

  • Albumin
  • Caprylate
  • Stability
  • Viral inactivation

ASJC Scopus subject areas

  • Biotechnology
  • Bioengineering
  • Applied Microbiology and Biotechnology
  • Immunology and Microbiology(all)
  • Pharmacology

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