Regulators Approve Post-Approval Change Protocol for Endotoxin Testing: From LAL to Recombinant Methods

The U.S. Food and Drug Administration (FDA) has announced the approval of a Post-Approval Change Management Protocol (PACMP) that allows a manufacturer to transition from a traditional lysate-based bacterial endotoxins test using horseshoe crab-derived materials to a recombinant endotoxin testing method. The recombinant method does not require horseshoe crab-derived materials and supports the 3Rs principles of replacement, reduction and refinement of animal use.

The approved protocol can be used for multiple biological products across several therapy areas, including cancer, cardiovascular, respiratory and rare diseases. The assessment was conducted under the International Coalition of Medicines Regulatory Authorities (ICMRA) Collaborative Assessment Pilot. The European Medicines Agency (EMA) acted as the leading authority. The FDA, Australia’s Therapeutic Goods Administration, Health Canada, Japan’s Pharmaceuticals and Medical Devices Agency and Swissmedic also participated.

Under the pilot, the participating regulators reviewed the same proposed manufacturing change at the same time, coordinated their questions to the applicant and made their own independent regulatory decisions within a standard 120-day review timeline. The submission was filed in March 2026, and the review concluded with the approval of the PACMP in June 2026. All participating authorities reached aligned decisions within a few days of one another.

In its update dated 31 August 2026, the FDA writes that “this approval supports FDA’s efforts to reduce reliance on animal-derived materials, modernize product testing and work with international regulators while continuing to ensure product quality.”

In a LinkedIn post, the EMA states: “The success of the Collaborative Assessment Pilot helps lay the foundation for a more efficient, predictable and globally coordinated approach to assessing certain manufacturing changes.”