Masterarbeit

Heparin - Changes in regulatory requirements and consequences thereof ***

Bettina Bickel (2015)

Summary
Language: English
It is the characteristic of unfractionated Heparin that it effectively intervenes in the blood coagulation cascade, when applied parenterally. The resulting delay in blood clotting and its usually good tolerance are the basis for its prominent role in health care worldwide.
Within the past eight years, the regulatory framework for the active ingredient Heparin and its preparations significantly changed. Even though the classification of Heparin as biological active substance by the Co-ordination Group for Mutual Recognition and Decentralised Procedures – Human (CMDh) in June 2007 can be considered as rather formal clarification of existing legislation, it had a considerable impact on dossier requirements and related regulatory maintenance activities such as the variation classification.
However, by far the most relevant adaptions were introduced as a necessary consequence of a worldwide Heparin scandal with severe adverse reactions caused by falsified Heparin batches in early 2008. Further to immediate precautionary measures, the European Pharmacopoeia monographs for Heparin sodium and Heparin calcium were repeatedly revised (twice via rapid implementation) in order to allow adequate proof of the absence of both, the identified contaminant oversulphated chondroitin sulphate (OSCS) and other potential impurities. In addition, the recent Guideline on the use of starting materials and intermediates collected from different sources in the manufacturing of non-recombinant biological medicinal products published by the Committee for Medicinal Products for Human Use (CHMP) provides guidance on dossier and Good Manufacturing Practice (GMP) requirements for the active substance Heparin.
This thesis outlines the changes in dossier, analytical and GMP requirements starting from the classification of Heparin as biological active substance to the stepwise restrictions following the Heparin scandal with focus on the European requirements. In this context the consequences of the alterations and associated challenges especially for the pharmaceutical industry are described. Finally, the recommendations from the CHMP regarding relevant dossier and GMP documentation for Heparin are discussed.
Pages: 49
Annex: pages: 6