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Contaminated Heparin Used in Trillium Coatings Applied to Selected Cardiopulmonary Bypass Products
Date: 2008-05-07
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The Health Products and Food Branch (HPFB) posts on the Health Canada web site safety alerts, public health advisories, press releases and other notices as a service to health professionals, consumers, and other interested parties. These advisories may be prepared with Directorates in the HPFB which includes pre-market and post-market areas as well as market authorization holders and other stakeholders. Although the HPFB grants market authorizations or licenses for therapeutic products, we do not endorse either the product or the company. Any questions regarding product information should be discussed with your health professional. This is duplicated text of a letter from Medtronic of Canada Ltd. |
| NOTICE TO HOSPITALS Health Canada Endorsed Important Safety Information on Contaminated Heparin Used in Trillium Coatings Applied to Selected Cardiopulmonary Bypass Products |
May 7, 2008
To: Hospital Chief of Medical Staff
Please distribute to the relevant Departments of [Surgery; Emergency Medecine, Pharmacy, Pediatrics, Anesthesia, Geriatrics, Internal Medicine, Nursing, Dentistry, Intensive Care and/or other Departments as required] and other involved professional staff and post this NOTICE in your institution.
| Subject: | Medical Device Notification - Contaminated Heparin Used in Trillium® Coatings Applied to Selected Cardiopulmonary Bypass Products |
Dear Health Care Professional,
This letter is to advise you that certain Trillium®1-coated Medtronic cardiopulmonary bypass (CPB) products (e.g. oxygenators, reservoirs, pumps and tubing packs) were manufactured with heparin batches contaminated with oversulfated chondroitin sulfate (OSCS). Based upon currently available information, we have determined that Medtronic Trillium®-coated products can continue to be used in cardiopulmonary bypass procedures.
Medtronic's heparin supplier recently reported that it had provided some batches of heparin to Medtronic which were contaminated with OSCS. Medtronic has no evidence linking the use of Trillium®-coated CPB products to OSCS related adverse events. We are informing you because OSCS is not intended to be a component material of our Trillium® coating and because OSCS has been reported to cause patient adverse events when injectable formulations of contaminated heparin are given in sufficient doses. Affected Trillium®-coated products have been distributed since January 24, 2008. A listing of affected product lots can be found at medtronic.
Background
The US regulatory agency, the Food and Drug Administration (FDA), has recently received numerous adverse event reports potentially caused by systemically administered, contaminated heparin, including acute hypotension, allergic response type symptoms and death. On April 8, 2008, FDA issued an important notice to manufacturers of medical devices urging that they re-evaluate their heparin supplies using FDA-recommended test methods.
Risk Evaluation
Medtronic has evaluated the potential clinical impact that may result from the use of, or exposure to, our heparin-containing Trillium® surface coatings. Our findings have determined:
- The coating process chemistry provides reasonable assurance that OSCS, if present, can only exist in trace quantities on finished product. Based upon the chemical structure of OSCS and the related manufacturing process chemistry, we do not expect OSCS to bind to product surfaces. Chemical rinse steps in the coating process provide further assurance that free and loosely-bound molecules would be removed during the manufacturing process.
- Using the most sensitive assays available, our analytical testing has not detected the presence of OSCS in simulated product use testing on samples produced with contaminated lots of heparin. While we have been unable to detect OSCS with our analytical testing, the analysis and detection of OSCS is subject to assay sensitivity limitations. Due to these limitations, we are unable to verify that contamination is completely absent from the surfaces of affected devices.
- Patient heparin exposure resulting from product use (100-200 units in a Trillium®-coated CPB circuit) is far less than typical heart surgery systemic heparin doses (10,000-40,000 units) and typical doses for other procedure types (e.g. kidney dialysis) where adverse events have been reported. FDA has observed that reported adverse events are associated with larger heparin doses than those potentially resulting from exposure to our Trillium®-coated CPB products.
- US FDA scientists and independent researchers recently determined the probable biologic mechanism underlying the adverse events associated with OSCS exposure. This work, published in the New England Journal of Medicine, presented in vitro experimentation data in which no biologic response was activated below 0.025 micrograms of OSCS per milliliter of plasma2. The applicability of these test results to OSCS exposure in heparin coatings, such as our Trillium® coated products, has not been proved. The quantity of OSCS available for binding to product (and thus subsequently available for patient exposure) using the Trillium® coating process is at least fifty times less than the threshold dose level presented in this journal article.
Based upon currently available information, including the factors listed above, we have determined that Medtronic Trillium®-coated products can continue to be used in cardiopulmonary bypass procedures.
Recommendations to healthcare professionals for patient care
As recommended in Health Canada's Notice to hospitals dated March 27, 2008, physicians exposing patients to heparin should continue to "monitor the patients for adverse events, particularly hypotension and signs and symptoms of hypersensitivity, and ensure that resuscitation equipment is available." Should your patients experience these symptoms, you should treat them using your standard procedures.
If you have any further questions concerning the execution of Trillium-coated CBP products notification, please contact your local Medtronic Representative or Medtronic Customer Service Representative at 1-800-268-5346, Monday - Friday, 8:00 a.m. to 5:00 p.m. EST.
This investigation is dynamic and ongoing at FDA and within Medtronic. We will continue to monitor this situation closely and advise you of significant new developments affecting Medtronic products.
Medtronic Carmeda®-coated CPB products also contain heparin. A separate communication provides information pertaining to Medtronic's Carmeda®-coated products.
Medtronic of Canada Ltd. For other inquiries related to this communication, please contact Health Canada at: |
Health Canada has been notified of this action.
We understand that you depend on us to support your practice by reliably providing the highest quality medical devices. We apologize for the inconvenience caused by this Medical Device notification.
Sincerely,
Original signed by
Jon Olsen
Director, Sales & Marketing
Cardiovascular Surgery Products
Medtronic of Canada Ltd.
References:
1. Technology license under agreement from BioInteractions, Limited, United Kingdom
2. 
Kishimoto TK, Viswanathan K, Ganguly T, et al.Contaminated Heparin Associated with Adverse Clinical Events and Activation of the Contact System. N Engl J Med 2008;358
