International Collaboration to Advance New Testing Methods That Reduce Reliance on Horseshoe Crab Blood

[8/31/2026] FDA, working with international regulatory partners through the International Coalition of Medicines Regulatory Authorities (ICMRA), has completed a collaborative assessment of a new testing approach for biological products that could reduce reliance on horseshoe crab blood while continuing to ensure product quality.

This assessment is part of the ICMRA Collaborative Assessment Pilot, which brings participating international regulators together to review proposed manufacturing changes at the same time, coordinate their questions to applicants, and make their own independent decisions within a standard 120-day review timeline. The pilot was established to improve consistency in regulatory expectations, reduce duplicative submissions and assessments, and facilitate more timely patient access to medicines.

Endotoxins are harmful substances released by certain bacteria that can cause serious adverse reactions in patients; testing for their presence is a critical safety and quality step in manufacturing biological products. The collaborative assessment evaluated the use of a recombinant endotoxins test as an alternative to the traditional Limulus Amebocyte Lysate (LAL) test, which relies on blood from horseshoe crabs. The submission, structured as a Post-Approval Change Management Protocol (PACMP), covered several biological products across multiple therapy areas, including cancer, cardiovascular, respiratory, and rare diseases. Recombinant endotoxins testing does not require horseshoe crab-derived materials and supports the 3Rs principles of replacement, reduction, and refinement of animal use, consistent with FDA's broader commitment to modernizing pharmaceutical testing and reducing reliance on animal-derived materials.

FDA participated in this assessment with international partners - Australia’s Therapeutic Goods Administration, Health Canada, Japan’s Pharmaceuticals and Medical Devices Agency, and Swissmedic, with the European Medicines Agency serving as the leading authority for this submission under the pilot. The review concluded with the approval of the PACMP in June 2026. All participating authorities reached aligned decisions within days of each other, which is a significant achievement in international regulatory coordination.

This collaborative approach allows regulators to share scientific expertise, coordinate discussions, and evaluate new approaches while making their own independent regulatory decisions. It can also reduce duplicative regulatory work, improve predictability and support more efficient review of certain manufacturing changes.

“No single regulatory authority can address the challenges facing the global pharmaceutical supply chain alone,” said Michael Kopcha, Director of the Office of Pharmaceutical Quality in FDA’s Center for Drug Evaluation and Research. Collaboration among international regulators is key to sharing expertise, supporting innovation, and advancing approaches that benefit the U.S. patients.”

FDA will continue working with international partners to support modern testing methods and approaches that advance pharmaceutical quality while protecting public health. Work is underway to build on the pilot and develop a more sustainable, globally coordinated regulatory approach.