Collaborative study for the establishment of erythropoietin BRP batch 3

Area of Science:

• Pharmacopoeial Science
• Biotechnology
• Analytical Chemistry

Background:

• The European Pharmacopoeia (Ph. Eur.) monograph 1316 requires reference preparations for erythropoietin (EPO) testing.
• The existing EPO Biological Reference Preparation (BRP) needed replacement to ensure analytical continuity.

Purpose of the Study:

• To establish a new EPO BRP batch (BRP3) through a collaborative study.
• To qualify BRP3 for use in Ph. Eur. monograph 1316 identification and assay methods.
• To assign unitage for BRP3 relative to international standards and previous batches.

Main Methods:

• A collaborative study involving 16 international laboratories.
• Biological (in vivo mouse bioassay) and physicochemical assays were performed.
• Candidate BRP batch 3 (cBRP3) was tested against BRP batch 2 (BRP2) and WHO International Standards.

Main Results:

• BRP3 was demonstrated to be suitable for EPO quality control as per Ph. Eur. monograph 1316.
• Unexpected results in mouse bioassays for BRP2 and cBRP3 necessitated careful potency assignment.
• Potency of cBRP3 was assigned against BRP2 to maintain unitage continuity, resulting in an assigned potency of 35,280 IU/vial.

Conclusions:

• The established BRP3 is appropriate for use as a reference standard for erythropoietin concentrated solutions.
• Continuity of unitage was ensured by assigning BRP3 potency relative to BRP2.
• BRP3 is suitable for multiple pharmacopoeial applications, including bioassays and identification tests.