Information on Heparin

Please report all adverse events associated with heparin to MedWatch

Serious injuries and deaths have been associated with the use of heparin, a blood-thinning drug that contained active pharmaceutical ingredient (API) from China. The adverse events have included allergic or hypersensitivity-type reactions, with symptoms such as low blood pressure, angioedema, shortness of breath, nausea, vomiting, diarrhea, and abdominal pain.

In February 2008, Baxter Healthcare Corporation recalled multi-dose and single-dose vials of heparin sodium for injection, as well as HEP-LOCK heparin flush products. After launching a far-ranging investigation, FDA scientists identified a previously unknown contaminant in the heparin. Contaminated heparin has also been found in association with some medical devices, such as certain catheters. Some of these medical devices have been recalled. For additional information about potentially contaminated medical devices and recalls, please refer to the Center for Devices and Radiological Health Questions and Answers. The agency is continuing to aggressively investigate the situation.

General Information

• Questions and Answers
• News and Press Conferences
• FDA's Role

Information for Healthcare Providers and Facilities

• Information for Healthcare Professionals and Facilities
• Public Health Advisories and Updates
• Recalls
• Adverse Event Reports

Information for Manufacturers

• Notices to Manufacturers/Initial Distributors of Medical Devices
• Screening Methods
• Heparin Test Results
• Inspectional Observations
• Warning Letters
• Countries with Contaminated Heparin API

Questions and Answers

• Updated Questions and Answers on Heparin Sodium Injection (Baxter) (6/18/2008)
• Questions and Answers on Heparin, Medical Devices and In-vitro Diagnostic Assays (6/3/2008)

News and Press Conferences

• FDA News (2/11/2008)
• Transcripts of FDA Press Conferences on Adverse Events Associated with Baxter Healthcare Corporation's Multiple-Dose Vials of Injectable Heparin

FDA's Role (3/14/2008)

• Heparin, Adverse Reactions
• Heparin, Analyzing the Contaminant
• Heparin, Import Alert

Information for Healthcare Professionals and Facilities

• Information About Heparin and Plasma Derived Products
• Update to Healthcare Facilities and Healthcare Professionals about Heparin and Heparin-containing Medical Products
• Medical Devices and Diagnostic Products that May Contain or Be Coated with Heparin
• Heparin Update to MedWatch Partners (5/9/2008)

Public Health Advisories and Updates

• Public Health Update: Recall of Heparin Sodium for Injection (2/28/2008)
• Public Health Advisory (2/11/2008)

Recalls

• Medtronic Initiates Voluntary Field Actions for Selected Heparin-Coated Products Used During Cardiopulmonary Bypass (5/14/2008)
• Covidien Initiates Voluntary Recall of Pre-Filled Syringes Containing Heparin (3/28/2008)
• B. Braun's Supplier Recall of Heparin API Prompts Voluntary Recall of Heparin Solutions (3/21/2008)
• American Health Packaging Announces a Recall of Approximately 1,400 Units of Heparin Sodium Vial Products as Part of Broader Baxter Recall (3/20/2008)
• Baxter to Proceed with Recall of Remaining Heparin Sodium Vial Products (2/28/2008)
• Baxter Issues Urgent Nationwide Voluntary Recall of Heparin 1,000 Units/ml 10 and 30ml Multi-Dose Vials (1/25/2008)

Adverse Event Reports

• Information on Adverse Event Reports and Heparin

Notices to Manufacturers/Initial Distributors of Medical Devices

• Suggested Analytical Testing Protocol for In Vitro Diagnostic Devices Manufactured with Heparin Contaminated With Oversulfated Chondroitin Sulfate (updated 6/13/2008)
• Important Notice to Manufacturers and Initial Distributors of Medical Devices That May Contain Heparin Or Are Heparin-Coated (4/9/2008)
• Follow-up Notice to Heparin Device Manufacturers and Initial Distributors (5/9/2008)
  

Screening Methods

** New Information ** (7/7/2008)

The United States Pharmacopeia (USP) has recently published updated compendial test methods for heparin sodium USP to include the two screening tests previously posted on FDA’s website. Effective immediately, in accord with section 501(b) of the FD&C Act, all heparin sodium USP must meet compendial requirements as specified at the following link http://www.usp.org/hottopics/heparin.html.

All other measures used to prevent contaminated heparin products from entering the US should remain in place, and we request that all heparin suppliers and manufacturers continue reporting results to FDA as outlined in the section "Heparin Test Results" until further notice.

Heparin Test Results

To ensure the safety of heparin products in the United States market, the FDA has asked companies that manufacture heparin-containing products to test the heparin active pharmaceutical ingredient (API) used in those products using capillary electrophoresis (CE) and the updated proton nuclear magnetic resonance (H-NMR) methods provided in the “Screening Methods” section of this website.  As part of FDA’s ongoing investigation, the FDA has updated the information it is requesting from manufacturers to allow a better understanding of the complex global heparin supply chain and to ensure the safety of heparin containing products for use in the United States.  

In order to promote consistency in the information reporting and gain the most benefit from these reporting activities, the FDA is requesting monthly updates from manufacturers on all heparin API testing using the template provided below. However, FDA should be notified of any positive results within 3 days of the test being conducted.  In addition, FDA requests that  manufacturers submit the associated NMR spectra and CE electropherograms that support the testing results to the address below.

Please send all test results to the U.S. FDA at:  cderrecalls@cder.fda.gov using the following template (in Microsoft Excel format).

Heparin Analytical Result Reporting Sheet.xls

FDA has provided the following sample spreadsheet in order to illustrate proper use of the spreadsheet.

SAMPLE Heparin Analytical Result Reporting Spreadsheet.xls

Inspectional Observations

• FDA-483 on Heparin (2/28/2008)

Warning Letters

• Changzhou SPL Company, Ltd. (4/21/2008)

Countries with Contaminated Heparin API (4/21/2008)

• Countries with Contaminated Heparin API

Back to Top     Back to Drug Index

PDF requires the free Adobe Acrobat Reader

Date created: February 11, 2008, updated September 25, 2008

CDER Home Page | CDER Site Info | Contact CDER | What's New @ CDER
FDA Home Page | Search FDA Site | FDA A-Z Index | Contact FDA | Privacy | Accessibility | HHS Home Page

FDA/Center for Drug Evaluation and Research