Collaborative study for the establishment of erythropoietin BRP batch 5

Area of Science:

• Pharmacology
• Biotechnology
• Analytical Chemistry

Background:

• The European Pharmacopoeia (Ph. Eur.) Biological Reference Preparation (BRP) for erythropoietin (EPO) is crucial for potency determination using in vivo bioassays.
• Stocks of the current BRP batch 4 (BRP4) are depleted, necessitating a replacement standard.
• Previous BRP4 vials contained excess material, leading to potential waste during bioassays.

Purpose of the Study:

• To calibrate a new EPO BRP batch (BRP5) in International Units (IU) against the 3rd WHO International Standard.
• To establish a reference preparation with a lower EPO content to minimize waste.
• To ensure continuity of the International Unit for EPO potency measurements.

Main Methods:

• A collaborative study involving eight international laboratories was conducted.
• The candidate material was calibrated against the 3rd WHO International Standard for recombinant erythropoietin (11/170).
• In vivo bioassays, specifically polycythaemic and normocythaemic mouse bioassays, were employed for potency determination.

Main Results:

• The European Pharmacopoeia Commission adopted the new standard as Erythropoietin BRP batch 5 in June 2018.
• The assigned potency for Erythropoietin BRP batch 5 is 2000 IU/ampoule.
• The potency of the previous BRP batch 4 was confirmed, ensuring continuity of the International Unit.

Conclusions:

• Erythropoietin BRP batch 5 is established as the official reference preparation for specific EPO bioassays.
• The new batch addresses the need for a standard with reduced EPO content, optimizing its use.
• The study confirmed the reliability and continuity of EPO potency measurements using the established reference standards.