Information on Heparin Sodium Injection

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, 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. The agency is continuing to aggressively investigate the situation.

• FDA's Role
• Adverse Event Reports
• Notices to Manufacturers/Initial Distributors of Medical Devices
• Information for Healthcare Professionals and Facilities
• Heparin Test Results
• Inspectional Observations
• News and Press Conferences
• Public Health Advisories and Updates
• Questions and Answers
• Recalls
• Warning Letters
• Screening Methods
• Countries with Contaminated Heparin API

FDA's Role (3/14/2008)

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

Adverse Event Reports (4/8/2008, updated 4/21/2008)

• Information on Adverse Event Reports and Heparin

Notices to Manufacturers/Initial Distributors of Medical Devices

• 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)
  

Information for Healthcare Professionals and Facilities

• 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)

Heparin Test Results

Please send all test results to the U.S. FDA at: cderrecalls@cder.fda.gov or call 301-796-3358.

Please provide the following information regarding heparin testing:

1. Name
2. Company
3. Telephone number
4. Email address
5. Lot # of heparin sample
6. Date heparin sample was manufactured
7. Source of Heparin: API, Finish Product, Crude/Bulk, or Other
8. Proton NMR Results (FDA Web Page Method): Two Peaks (Yes/No) – Date performed
9. Capillary Electrophoresis (FDA Web Page Method): Two Peaks (Yes/No) – Date performed
10. Additional Tests performed
11. Comments on results of test data
12. Conclusion: FAIL (Suspect or Atypical) or PASS (Not Suspect or Typical)
13. Heparin Sample associated with increased Adverse Events (Yes/No/Unknown)

Inspectional Observations

• FDA-483 on Heparin (2/28/2008)

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

Public Health Advisories and Updates

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

Questions and Answers

• Updated Questions and Answers on Heparin Sodium Injection (Baxter) (3/7/2008)
• Question and Answers (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)

Warning Letters

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

Screening Methods (3/6/2008)

Please send all test results to the U.S. FDA.

• Impurity Evaluation of Heparin Sodium by Capillary Electrophoresis
• Impurity Evaluation of Heparin Sodium by ¹H-NMR Spectroscopy (updated 4/8/2008)

In early February, after learning about a spike in adverse events involving this product, FDA launched a far ranging investigation in both the United States and abroad. This included inspecting Baxter's domestic facilities, examining Heparin product in the United States and sending a team of experts to China to conduct a comprehensive inspection of the Changzhou SPL facility that makes the active ingredient for this drug.

While the FDA has yet to determine the root cause of these adverse events, we have found a Heparin-like compound that is not Heparin present in some of the Heparin Active Pharmaceutical Ingredient (API) produced by Scientific Protein Labs, which maintains a facility in Wisconsin in addition to the Changzhou plant.

This contaminant is present in significant quantities, accounting for 5 to 20 percent of the total mass of each sample tested. It reacts like Heparin in many tests, which is why the traditional release tests did not detect it.

At this point, we don't know how the Heparin-like compound got into the Heparin Active Pharmaceutical Ingredient, but we are continuing to aggressively investigate the situation.

We don't yet have proof that this contaminant is causing the adverse events. There is an association, but not a direct causal link at this time.

To ensure that all is being done to provide a safe supply of this life-saving drug, we are releasing information on two tests that manufacturers and regulators can use to screen for this contaminant.

The two methods include proton nuclear magnetic resonance (H-1 NMR) and capillary electrophoresis (CE). The tests are to be used for ALL Heparin Sodium API prior to batch release. The API material is considered contaminated if there is a doublet peak at 2.1 ppm in H-1 NMR and a shoulder peak in CE, as illustrated in the two attachments. Heparin sodium API must contain only a single peak (singlet) at 2.1 ppm in NMR and a single peak in CE. It is recommended that both screening methods (H-1 NMR and CE) be used in addition to the regulatory and/or compendial specification requirements.

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

• Countries with Contaminated Heparin API

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Date created: February 11, 2008, updated May 14, 2008

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