A collaborative study to establish the 5th International Standard for Unfractionated Heparin

Area of Science:

• Biochemistry
• Pharmacology
• Laboratory Medicine

Background:

• The 4th International Standard for Unfractionated Heparin (82/502) required calibration of a replacement.
• Standardization is crucial for ensuring consistent therapeutic efficacy and safety of heparin products.

Purpose of the Study:

• To collaboratively calibrate and evaluate two candidate materials (A and B) as a replacement for the 4th International Standard for Unfractionated Heparin.
• To determine the most suitable candidate for the 5th International Standard based on assay performance and material characteristics.

Main Methods:

• Twenty-four laboratories participated in a collaborative study.
• Candidate materials A and B were assayed against the 4th International Standard using various methods.
• Intra- and inter-laboratory variations, potency estimates, and method variations were analyzed.

Main Results:

• Both candidate materials demonstrated excellent intra- and inter-laboratory reproducibility (mean %gcv <10%).
• No significant differences in potency estimates were observed between methods, though the USP method yielded lower potencies.
• Candidate A exhibited slightly lower inter-method variation compared to candidate B.

Conclusions:

• Candidate materials A and B showed marginal differences, with both performing well in the calibration study.
• Candidate A (97/578) was selected as the 5th International Standard for Unfractionated Heparin based on its narrower molecular weight profile, higher specific activity, and lower inter-method variation.
• Candidate A was officially accepted by the World Health Organization's Expert Committee on Biological Standardisation in October 1998, with an assigned potency of 2031 IU/ampoule.