Questions and Answers on Heparin, Medical Devices and In-vitro Diagnostic Assays
FDA’s Center for Devices and Radiological Health (CDRH) is concerned about the safety and effectiveness of medical devices that may be affected by heparin contaminated with oversulfated chondroitin sulfate (OSCS), and the possible effects the contaminant may have on the accuracy of in-vitro diagnostic (IVD) assays. In order to minimize the risks associated with use of this product, CDRH is providing recommendations to physicians and healthcare providers to avoid use whenever possible of products containing, coated with or affected by heparin found to be contaminated with OSCS.
1. What adverse reactions could contaminated heparin in medical devices cause in patients?
Based on experiences with injectable drug products, the contaminated heparin could be associated with various clinical events including severe allergic reactions, gastrointestinal symptoms (nausea, vomiting, abdominal pain, and diarrhea) and/or very low blood pressure. Although it is also possible that contaminated heparin may cause inaccurate results of in-vitro diagnostic tests (IVDs) that utilize heparin either as part of the assay or as part of the specimen collection, to date no testing problems have been reported. Because clinical care decisions might be based on inaccurate test results, laboratories and clinicians should continue to follow usual quality control practices to assure that tests generated are reliable.
2. Have heparin-related adverse events been reported from the use of any medical devices?
FDA’s Center for Devices and Radiological Health (CDRH) has been reviewing the reports in its post-market database for heparin-related adverse events with medical devices. CDRH has received 97 reports for adverse events associated with heparin-containing devices that occurred between January 1, 2008 and May 14, 2008. These include 11 deaths and 86 non-fatal events. The majority (82%) of reports were associated with use of heparin lock flush solutions although reports have also been received for other medical devices including heparin-coated oxygenators and circuits used during cardiopulmonary bypass procedures and heparin-coated vascular grafts. Sixty-nine (69) of the 97 reports noted the presence of at least one allergic, gastrointestinal, and/or hypotensive symptom following use of the device.
FDA has not determined conclusively that contaminated heparin in medical devices caused these events. The fact that someone reports an adverse event does not necessarily mean that the medical device, or the heparin it contains, caused the event. Likewise, symptoms reported in association with a death are not necessarily the cause of the death. Many patients have other serious conditions, or may be receiving other therapies that could have contributed to the reported event. In addition, it is uncertain at this time whether the devices cited in the reports contained contaminated heparin or not.
CDRH will continue to analyze the adverse event reports it receives for heparin-containing medical devices and will update this information periodically.
3. Which medical devices and products might be affected by the heparin problem?
Some medical devices contain and/or are coated with heparin, and some IVDs are manufactured using heparin. CDRH and manufacturers are aware that some devices have been affected by the recent contamination. Products coated with, containing or manufactured with heparin that may be affected include:
- Heparin lock flush solutions in vials and solutions in pre-filled syringes
- Devices used during cardiopulmonary bypass procedures, including certain oxygenators, filters, reservoirs, and cannulae
- Catheters including certain vascular access catheters, drainage, retransfusion and thermodilution catheters, and oximetry probes
- Certain vascular stents and grafts
- Certain assisted reproduction media devices
- Certain In-Vitro Diagnostic media and related devices (see next question)
- A list of other medical devices that may contain or be coated with heparin
4. Which in-vitro diagnostic devices (IVDs) might be affected by the heparin problem?
IVDs that may be affected include specialized devices such as tests that measure heparin’s effect in the body, and more general and widely used devices such as tubes containing heparin that are used to collect unclotted blood for various kinds of testing. Other examples include the following:
- IVDs that are used to monitor (or are affected by) heparin that has been injected into patients
- IVDs that incorporate heparin as part of the device itself
- IVDs that rely on heparin as part of the manufacturing process
5. Where can I find a list of recalled products?
A list of recalled products is available here: http://www.fda.gov/cder/drug/infopage/heparin/#recalls
6. What is FDA (CDRH) doing to ensure that medical devices containing heparin are not affected?
FDA (CDRH) has contacted manufacturers of medical devices and IVDs that contain heparin, or use heparin during the manufacturing process, to alert them that their products may potentially be affected by contaminated heparin. CDRH has requested that manufacturers take the following immediate actions premarket and post market:
- Firms should determine which specific product(s) they manufacture or distribute, in unfinished or in final form, that contain heparin or utilize heparin during processing. No further action is needed if a firm does not manufacture or distribute these products.
- For firms that manufacture or distribute ANY product that contains heparin, or is heparin coated, it is important to ensure that the heparin is contaminant-free using the FDA recommended test methods before the product is released. For more information about these recommended test methods, please see “Screening Methods” at http://www.fda.gov/cder/drug/infopage/heparin/default.htm.
- Report any adverse reactions related to the use of heparin that have or may have caused or contributed to a death, serious injury, or malfunctions that would be likely to cause or contribute to a death or serious injury.
- Assure that appropriate purchasing controls and acceptance activities are in place that provide reasonable assurance of the safety and effectiveness of your device on a continuing basis prior to marketing your device.
7. What actions is FDA (CDRH) recommending for health care professionals?
- Be alert to unexpected anaphylactic reactions in patients with heparinized devices/products/treatments and be prepared to treat appropriately.
- Be alert for inexplicable diagnostic results (false positives/false negatives).
- Promptly report any symptoms/problems that you believe may be due to the heparin within a medical device to FDA’s MedWatch Adverse Event Reporting program online at http://www.fda.gov/MedWatch/report.htm, by phone at 1-800-FDA-1088, or by returning the postage-paid FDA Form 3500, which may be downloaded from www.fda.gov/MedWatch/getforms.htm, by mail to MedWatch, 5600 Fishers Lane, Rockville, MD 20852-9787 or by fax at 1-800-FDA-0178.
- Contact the device manufacturer or the distributor for instructions on disposal and/or replacement of devices that may contain contaminated heparin.
8. What should consumers do if they believe they have an affected product?
- If you use heparin lock-flush solution for yourself or are a caregiver of a patient that uses lock-flush solution, be sure that you have disposed of any recalled product. Ask your health care provider about a replacement lock-flush solution.
- A list of recalled products is available here: http://www.fda.gov/cder/drug/infopage/heparin/#recalls
- Contact your health care provider if you are concerned about other medical devices that may be affected by contaminated heparin. (Note: link text for "other medical devices back to list in Question 1)
9. Where can I find more information about the heparin problem?
- General information about the heparin problem is posted at http://www.fda.gov/cder/drug/infopage/heparin/default.htm