EMEA Report Assesses Contaminated-Heparin Risk

June 12, 2008
Pharmaceutical Technology Editors

ePT--the Electronic Newsletter of Pharmaceutical Technology

In an assessment report about medicinal products containing heparin, the European Medicines Agency (EMEA)'s Committee for Medicinal Products for Human Use (CHMP) said it could not draw firm conclusions about the level of risk associated with unfractionated heparins (UFH) contaminated with oversulfated chondroitin sulfate (OSCS). Nevertheless, CHMP recommended that contaminated lots be withdrawn completely.

London (May 30)-In an assessment report about medicinal products containing heparin, the European Medicines Agency (EMEA)’s Committee for Medicinal Products for Human Use (CHMP) said it could not draw firm conclusions about the level of risk associated with unfractionated heparins (UFH) contaminated with oversulfated chondroitin sulfate (OSCS). Nevertheless, CHMP recommended that contaminated lots be withdrawn completely.

CHMP said that the adverse-event reports received to date were an insufficient basis for a risk assessment of OSCS-contaminated UFH. The data do not permit a dose-relationship assessment or support the development of risk-minimization measures, according to the report.

The adverse reactions led to episodes that resembled anaphylaxis. Most episodes were successfully treated with vasopressors, oxygen therapy, and steroids. The report noted that anaphylaxis is a recognized side effect of UFH treatment and that it was impossible to distinguish between adverse events caused by heparin itself and those caused by OSCS contamination.

CHMP said the number of adverse-event reports related to low molecular-weight heparins (LMWH) has not increased since the contaminated batches were marketed. So far, the only marketed LMWH known to be contaminated with OSCS is enoxaparin. The report advised healthcare professionals not to administer enoxaparin by the intravenous route until the supply chain is free of contamination.

The report urged prescribers who must administer contaminated enoxaparin to be aware that patients may exhibit severe allergic reactions. Prescribers should be prepared to treat these reactions with standard therapies such as vasopressors and steroids.

CHMP recommends a coordinated EU approach to investigating and inspecting the heparin supply chain, in collaboration with international partners such as China. The review should encompass finished-product manufacturers, active-substance suppliers, intermediate suppliers, distributors, and brokers, according to the report.

The committee also calls for the European Pharmacopoeia’s heparin monographs to be updated to include specific tests for OSCS and other possible contaminants.

The assessment report was a response to Germany’s request for a CHMP opinion on appropriate strategies to manage the recently detected heparin contamination. Germany submitted its request on Apr. 24, 2008, after several EU member states found a contaminant in certain batches of heparin.