News Brief: USP Adopts Recombinant Reagents for BET; Draws Commendations
The U.S. Pharmacopeia announced on July 26 that its Microbiology Expert Committee approved the inclusion of Chapter <86> Bacterial Endotoxins Test Using Recombinant Reagents. The chapter will be published for early adoption in November and will become official in May 2025.
Chapter <86> is intended to provide manufacturers with the information needed to use non-animal derived reagents. Manufacturers that currently use limulus amebocyte lysate (LAL) for endotoxin testing can continue to do so and Chapter <86> has no impact on them.
The bacterial endotoxins tests described in the new chapter are additional techniques to the current tests described in Chapter <85> Bacterial Endotoxins. The new chapter includes methods that use both recombinant cascade (rCR) and recombinant Factor C (rFC) reagents and provides information for manufacturers of new and existing pharmaceutical products on how to incorporate them into their quality testing.
USP noted in its announcement that the move reflects its “commitment to expanding the use of animal-free methods and materials.”
The Horseshoe Crab Recovery Coalition applauded USP’s decision in a July 26 press release. “We are delighted that USP has provided guidance that will help place recombinant testing on equal footing with LAL,” added Larry Niles, co-founder of HCRC. “Recombinant testing provides a reliable, sustainable alternative that is critical to horseshoe crab conservation and a healthy ecosystem throughout the Atlantic coast.”
U.S. Rep. Frank Pallone, Jr. of New Jersey called on the pharmaceutical industry to “urgently transition” to the alternative test methods. "Horseshoe crabs’ habitat is experiencing greater environmental stress every day due to climate change. The entire endotoxin supply chain cannot be reliant on such a limited, fragile source when we now have reliable alternatives....I applaud the USP for taking action to make it easier for pharmaceutical manufacturers to start using safe alternatives just as the European Union and Japan have done for years."
The long-ranging debate over the “horseshoe crab” method spelled out in Chapter <85> and synthetic methods like Factor C to be included in Chapter <86> played out in the PDA Letter over the years, with articles calling for the use of the latter as early as 2018 (1). In 2019, longtime LAL researcher, Dr. James Cooper, wrote that the tri-spine or Chinese horseshoe crab had gone on the International Union for Conservation’s endangered list (2). A 2020 article by the Horseshoe Crab Recovery Coalition called for LAL alternatives, citing the pharmaceutical industry’s own “3R principles” (Reduce/Refine/Replace) (3). A decade ago, this author wrote a feature-length piece for the September 2014 PDA Letter noting that the possible endangered status of the Red Knot shorebird might compel the U.S. EPA to protect the bird’s food source—the horseshoe crab (4).
Turn back to the PDA Letter for more details on this unfolding story.
References
- https://www.pda.org/pda-letter-portal/home/full-article/endotoxin-testing-using-recombinant-reagents
- https://www.pda.org/pda-letter-portal/home/full-article/tri-spine-crab-now-on-endangered-list
- https://www.pda.org/pda-letter-portal/home/full-article/covid-19-and-the-need-for-an-lal-alternative
- Walter Morris, “Will a Shorebird Knot Up Bacterial Endotoxin Assay Supplies?”, PDA Letter, September 2014.