A collaborative study designed to establish the 4th International Standard for Heparin

Area of Science:

• Biochemistry
• Pharmacology
• Clinical Chemistry

Background:

• The International Standard for Heparin is crucial for accurate heparin dosage and therapeutic monitoring.
• Previous standards may require replacement due to variations in manufacturing or evolving analytical methods.

Purpose of the Study:

• To establish a new, reliable International Standard for Heparin through a global collaborative study.
• To evaluate candidate heparin preparations using multiple assay methods to ensure consistency and accuracy.

Main Methods:

• An international collaborative study involving 22 laboratories.
• Analysis of 248 assays, including activated partial thromboplastin time (APTT), thrombin inhibition, anti-Xa assays, and pharmacopoeial assays.
• Bioassay comparison of candidate preparations against the existing standard.

Main Results:

• Less than 5% difference in mean potency estimates across all candidate preparations and assay methods.
• Freeze-dried preparation 82/502 showed the closest parallelism to the existing standard via bioassay.
• Preparation 82/502 was officially established as the 4th International Standard for Heparin by the World Health Organization (WHO).

Conclusions:

• Preparation 82/502 is a suitable replacement for the International Standard for Heparin.
• The established standard has an assigned unitage of 1780 international units (i.u.) per ampoule.
• This new standard will facilitate consistent and accurate heparin quantification globally.