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Nach dem TGN1412-Zwischenfall

Prinzipien der Bewertung von First-in-Man-Studien mit monoklonalen Antikörpern durch das Paul-Ehrlich-Institut

After the TGN1412 incident. Principles for assessment of first-in-man trials with monoclonal antibodies by the Paul Ehrlich Institute

  • Leitthema: Originalien und Übersichtsarbeiten
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Bundesgesundheitsblatt - Gesundheitsforschung - Gesundheitsschutz Aims and scope

Zusammenfassung

Der Einsatz monoklonaler Antikörper hat auf vielen klinischen Gebieten zu neuen therapeutischen Möglichkeiten geführt. Er birgt aber auch Risiken, wie das akute Auftreten eines Zytokinsturms bei der Erstanwendung von TGN1412, einem Superagonisten gegen CD28, im März 2006 gezeigt hat. Dieser Artikel beschreibt die Prinzipien, die das Paul-Ehrlich-Institut (PEI) bei der wissenschaftlichen Bewertung von Anträgen auf klinische Prüfung zur Erstanwendung von monoklonalen Antikörpern am Menschen anwendet. Diese werden als Verfahrensanweisung in das Qualitätsmanagementsystem des PEI implementiert und stellen eine Ergänzung und Konkretisierung der allgemeinen Leitlinie des Ausschusses für Humanarzneimittel (CHMP) für die Produktklasse der monoklonalen Antikörper dar. Wesentliche Aspekte sind die auf monoklonale Antikörper zugeschnittenen Faktoren zur Abschätzung des Risikos, da nicht jeder monoklonaler Antikörper per se ein Risiko darstellt, sowie die Gründung einer PEI-Expertengruppe, die die wissenschaftliche Bewertung begleitet und prüft.

Abstract

The use of monoclonal antibodies has led to new therapeutic possibilities for many clinical conditions. However, their application also bears risks, as demonstrated by the acute occurrence of a cytokine storm following administration of TGN1412, an anti-CD28 superagonist, in March 2006. This article highlights the principles of the Paul-Ehrlich-Institut (PEI) for the scientific assessment of first-in-man clinical trial applications for monoclonal antibodies. These principles are implemented as a standard operating procedure in the PEI Quality Management System and are intended as a supplement specific to monoclonal antibodies to the published general guideline issued by the Committee for Medicinal Products for Human Use (CHMP). Central aspects are the identification of risk factors for monoclonal antibodies based on defined criteria, since not every novel monoclonal antibody represents a risk per se. Furthermore, a PEI expert group that supports the scientific assessment procedure has been founded.

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Authors and Affiliations

  1. Paul-Ehrlich-Institut, Langen, BRD

    C. K. Schneider &  U. Kalinke

  2. Paul-Ehrlich-Institut, Paul-Ehrlich-Straße 51–59, 63225, Langen, BRD

    U. Kalinke

Authors
  1. C. K. Schneider
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  2. U. Kalinke
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Correspondence to U. Kalinke.

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Schneider, C.K., Kalinke, U. Nach dem TGN1412-Zwischenfall. Bundesgesundheitsbl. 50, 1213–1220 (2007). https://doi.org/10.1007/s00103-007-0331-6

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  • DOI: https://doi.org/10.1007/s00103-007-0331-6

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