Safety
This article was originally published in RAJ Devices
Executive Summary
Heparin contamination leads to warning for US device makers
Heparin contamination leads to warning for US device makers
Concerns over contaminated heparin have prompted the US Food and Drug Administration to tell manufacturers and distributors of medical devices that contain or are coated with the anticoagulant to take steps to ensure their products are safe1.
The FDA has received reports of 103 deaths following heparin administration since January 2007 and the agency is continuing to receive reports of adverse events occurring in patients after administration2. There have been recalls in the US and in other countries of contaminated heparin-containing products3-5.
The FDA's Center for Devices and Radiological Health says it is concerned about the safety and effectiveness of devices that may be affected by the contaminant, and the possible effects it may have on the accuracy of in vitro diagnostic assays. It is urging all device manufacturers and initial distributors of heparin-containing or -coated products to have all imported lots of heparin sodium active pharmaceutical ingredient tested by laboratories capable of performing FDA-recommended test methods.
Heparin, made from pigs' intestines, can be delivered through pre-filled syringes6. It is also found in vascular stents and grafts; devices used in cardiopulmonary bypass procedures, including certain oxygenators, filters, reservoirs, and cannulae; and in certain vascular access catheters, thermodilution catheters and oximetry probes. It may also be used in blood collection tubes for clinical laboratory analysis. In IVD tests, it is used as part of the assay or is added to the specimen.
More than 80 companies contacted
The FDA has to date alerted more than 80 device companies7. Manufacturers are being advised to perform nuclear magnetic resonance and capillary electrophoresis tests on relevant products before they are released. They are also being asked notify the FDA of all reports of any adverse events that could be linked to the heparin itself or to malfunctions in the device that may be caused by contaminated heparin.
Heparin-related adverse events may include allergic reactions, unexplained reduction in blood platelet count (thrombocytopenia), excessive haemorrhaging/anticoagulation, unexplained catheter/device thrombosis or spurious IVD test results.
In March, Wisconsin-based SPL Pharma recalled lots of heparin active pharmaceutical ingredient that were distributed to a number of device manufacturers. Products made from those lots are adulterated by the contaminant. At least one contaminant has been identified as oversulfated chondroitin sulphate.
The FDA says that a direct link between the contaminated heparin and the allergic reactions has not yet been established and that it is still trying to determine the root cause.
References
1. FDA notice, 8 April 2008, www.fda.gov/cdrh/safety/heparin-notice.html
2. FDA website, 8 April 2008, www.fda.gov/cder/drug/infopage/heparin/adverse_events.htm
3. TGA (Australia) press release, 27 March 2008, www.tga.gov.au/alerts/medicines/heparin.htm
4. Health Canada advisory notice, 20 March 2008, www.hc-sc.gc.ca//ahc-asc/media/advisories-avis/_2008/2008_49_e.html
5. Swissmedic press release, 20 March 2008, www.swissmedic.ch/en/fach/overall.asp?theme=0.00081.00001'theme_id=476&news_id=5276'page=1
6. Clinica World Medical Technology News, Online, 15 April 2008
7. Ibid