| Evaluation of the immuno-stimulatory potential of stopper extractables and leachables by using dendritic cells as readout. | |
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MedLine Citation:
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PMID: 19226629 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Recombinant protein pharmaceuticals may bear some risks and undesirable side effects, such as the appearance of immunogenic reactions. The increased incidence of antibody-mediated pure red cell aplasia (PRCA) outside the United States after administration of a human serum albumin (HSA)-free EPREX (recombinant human erythropoietin alpha) formulation was explained with the generation of rubber stopper related leachables, possibly acting as immunogenic adjuvants. In our study, we have investigated the potential of extractable and leachable preparations of three different pharmaceutical relevant stoppers to generate a "danger signal" in a dendritic cell assay. Furthermore, the investigated extractable and leachable preparations were characterized by NMR and a micelle-based polysorbate quantification method. In summary, we could demonstrate that stopper extractables, either generated by extraction or by leaching conditions, were not acting as danger signals for dendritic cells. Instead we identified degradation products of polysorbate 80, oleic acid and follow-up products, occur only under very accelerated conditions (100 degrees C for 4 days) as a potential stimulator for these immune cells. As this degradation did not occur at real-time, the authors however do not consider their finding to be linked to any direct safety implications of polysorbate-containing formulations in clinical practice. |
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Authors:
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Robert Mueller; Anette Karle; Anne Vogt; Harald Kropshofer; Alfred Ross; Karsten Maeder; Hanns-Christian Mahler |
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Publication Detail:
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Type: Journal Article |
Journal Detail:
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Title: Journal of pharmaceutical sciences Volume: 98 ISSN: 1520-6017 ISO Abbreviation: J Pharm Sci Publication Date: 2009 Oct |
Date Detail:
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Created Date: 2009-08-31 Completed Date: 2010-01-04 Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 2985195R Medline TA: J Pharm Sci Country: United States |
Other Details:
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Languages: eng Pagination: 3548-61 Citation Subset: IM |
Affiliation:
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F. Hoffmann-La Roche Ltd, Formulation R&D Biologics, Pharmaceutical and Analytical R&D, Basel, Switzerland. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Adjuvants, Immunologic
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chemistry*,
pharmacology* Algorithms Antigens, CD86 / analysis Chemistry, Pharmaceutical Chromatography, High Pressure Liquid Dendritic Cells / drug effects* Drug Contamination* Drug Packaging* Epoetin Alfa / analysis Excipients / analysis Humans Magnetic Resonance Spectroscopy Mass Spectrometry Micelles Monocytes / drug effects Oleic Acid / analysis Polysorbates / analysis Rubber / chemistry Spectrophotometry, Ultraviolet Up-Regulation / drug effects |
| Chemical | |
Reg. No./Substance:
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0/Adjuvants, Immunologic; 0/Antigens, CD86; 0/Excipients; 0/Micelles; 0/Polysorbates; 112-80-1/Oleic Acid; 113427-24-0/Epoetin Alfa; 9006-04-6/Rubber |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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