FDA announces plans to improve heparin safety

July 14, 2015

FDA's new draft guidance seeks to prevent heparin medication errors and ensure safety of heparin-containing medical devices and combination products.

The FDA issued a draft guidance document designed to prevent heparin medication errors and ensure safety of heparin-containing medical devices and combination products this week.

The United States Pharmacopeia (USP) drug substance monograph for Heparin Sodium, Heparin Lock Flush Solution, and Heparin Sodium Injection have recently undergone several revisions following serious and fatal events, according the agency’s “Heparin-Containing Medical Devices and Combination Productions: Recommendations for Labeling and Safety Testing”.

In addition, heparin has been identified as a high-alert medication by the Institute for Safe Medication Practices (ISMP), due to a heightened risk of patient harm when dosed incorrectly. And, the USP’s Safe Medication Use Expert Committee “recognized a recurring trend of medication errors related to misinterpretation of the expression of concentration on the labeling of injectable products, resulting in serious consequences to patients, including death,” the FDA wrote in the draft guidance document.

As a result, the guidance supports labeling statements on single-dose and multiple-dose Heparin Lock Flush Solution, expressing strength per total container volume as the primary expression of strength, following in close proximity by strength per mL in parentheses [eg, 100 USP Units/10 mL (10 USP Units/mL)].

For Heparin Lock Flush Solution products containing a volume of less than 1 mL, the strength per fraction of a mL should be the only expression of strength, such as 100 USP Units/0.5 mL.

For heparin-bonded products, the total amount of heparin per total surface area should be displayed on the primary package label, followed by the concentration per area unit in parentheses [eg, 100 USP Units/total surface area², (10 USP Units)/unit of surface area²].


Meanwhile, heparin product manufacturers should comply with several safety testing rules, according to the guidance. “Manufacturers of medical devices and combination products which include heparin must comply with the elements of safety testing that are required to be performed and documented as part of compliance with the Quality System (QS) regulations for devices…,” the guidance states.

In addition, manufacturers should follow the guidance document, “Heparin for Drugs and Medical Device use: Monitoring Crude Heparin for Quality”. Manufacturers’ premarket submissions should describe the heparin product in detail and document compliance with heparin safety testing, including the aforementioned guidance document.