What is the Scorecard point system and sustainability ratings?

What do the points mean?

The survey is organized into five categories. Each category describes a group of potential steps taken by companies to transition away from using horseshoe crab blood for drug and vaccine safety testing. Companies with points in multiple categories are further along in their transition to using synthetic alternatives.

• In Category 1, companies no longer use TAL, derived from the (already endangered) Asian Horseshoe Crab
• In Category 2, companies have publicly acknowledged and/or published data about the benefits of removing LAL from research and manufacturing processes.
• In Category 3, companies are significantly reducing the use of LAL (by at least 80%) in manufacturing processes via transition to synthetic alternatives for water testing and/or via microfluidics.
• In Category 4, companies are working to adopt, or have already adopted, synthetic alternatives for safety testing in the manufacturing of new applicable products.
• In Category 5, companies are working to adopt, or have already adopted, synthetic alternatives for safety testing in the manufacturing of legacy (previously registered) products.

Will the Scorecard continue to be updated?

Yes. We look forward to each company’s score improving as they continue to remove horseshoe crabs from their drug and vaccine manufacturing processes. We will update the Scorecard regularly as we learn about additional ways that companies are making the transition to synthetic alternatives. 

Why is it important for pharmaceutical companies to transition to synthetic alternatives?

The American Horseshoe Crab is currently listed as a “vulnerable” species by the International Union for the Conservation of Nature (IUCN) and its designation as a “U.S. Endangered Species” is under consideration by the National Marine Fisheries Services (NOAA Fisheries). 

The Atlantic States Marine Fisheries Commission (ASMFC) estimates mortality for bled horseshoe crabs at 15 percent, but independent studies show mortality could be as high as 30 percent, with additional effects beyond mortality that impact the population’s ability to spawn for one year. Harvesting horseshoe crabs for their blood now exceeds the bait harvest, with more than 1.1 million crabs being bled annually for pharmaceutical purposes. American Horseshoe Crabs play a critical role in coastal ecosystems in the United States, including the species’ vital importance to migratory shorebirds. 

What are the benefits for companies to adopt synthetic alternatives for safety testing?

Beyond its sustainability benefits, synthetic alternatives offer several advantages over traditional LAL tests:

• Equivalent Efficacy: synthetic solutions demonstrate equivalent effectiveness in detecting bacterial contaminants.
• Reduced False Positives: synthetic solutions eliminate the potential for false positives and elevated readouts associated with variations in horseshoe crab blood.
• Scalability and Consistency: synthetic solutions avoid supply chain constraints and ensure consistent results, unlike the variable nature of LAL tests.
• Alignment with 3Rs: Adopting synthetic alternatives align with the pharmaceutical industry’s commitment to the 3Rs (Replacement, Reduction, and Refinement) of animal testing.

How might a pharmaceutical company transition to synthetic alternatives for endotoxin testing?

 The transition would happen in stages. Here is a potential staged approach:

1. Prioritize Water Testing: Implement synthetic alternatives for lab water testing. Lab water testing has been shown to utilize approximately 80% of the use of LAL in large pharmaceutical manufacturing processes.
2. New Drug/Vaccine Development: Integrate synthetic alternatives into the development pipeline for testing new applicable drugs.
3. Legacy Drug/Vaccine Application: Once established, consider applying synthetic alternatives to testing legacy (previously registered) drugs/vaccines.

Where can I view the Scorecard?

Information about the Sustainability Scorecard is available at www.pharmascore.org. Beginning February 1, 2025, the Scorecard will display sustainability ratings for the top 50 pharmaceutical companies based on 2023 revenue.

Why is there a Scorecard now?

On November 1, 2024, the U.S. Pharmacopeia (USP) adopted and published endotoxin (contaminant) testing guidelines for the use of synthetic alternatives in lieu of horseshoe crab-derived Limulus amoebocyte lysate (LAL). 

Based on USP’s guidance, synthetic alternatives are now considered equivalent; in essence, creating a level playing field between the gold standard LAL and synthetic alternatives. Now pharmaceutical companies have the opportunity to do the right thing for patient safety, and for the protection of horseshoe crabs and the ecosystems that rely on this critical species.  

How will synthetic alternatives avoid supply chain issues? 

The increasing demand for vaccines, injectable medications, and infusion therapies to treat cancers, infectious diseases, diabetes, obesity, autoimmune conditions and other illnesses has led to a corresponding surge in the harvesting of horseshoe crabs for endotoxin (contaminant) testing. The adoption of synthetic alternatives to the blood of this declining species is crucial for ensuring a reliable and sustainable supply of endotoxin testing solutions without compromising patient safety.

How does the Scorecard reflect the critical role of 21st-century biotechnology for patient safety and wildlife conservation? 

Just as advances in biotechnology are fueling a revolution in drug discovery and development, biotechnology has also provided a sustainable and scalable safety testing solution in the form of synthetic alternatives to LAL. Synthetic alternatives are a proven solution that is fully scalable to meet rising product demand while supporting industry’s commitment to the 3Rs in animal testing (Replace, Reduce, Refine).

Who created the Scorecard? 

The Scorecard is a joint initiative of Revive & Restore, the Horseshoe Crab Recovery Coalition (HCRC), and the Center for Biological Diversity. 

• Revive & Restore is the leading wildlife conservation organization promoting the incorporation of biotechnologies into standard conservation practice. The Sausalito, California nonprofit was formed in 2012 with the idea that 21st century biotechnology can and should be used to enhance genetic diversity, build disease resistance, and facilitate adaptation. Its mission is to enhance biodiversity through the genetic rescue of endangered and extinct species. 
• The Horseshoe Crab Recovery Coalition (HCRC) is composed of more than 50 biomedical and conservation groups dedicated to ensuring the future of the American Horseshoe Crab. In addition to the Center for Biological Diversity and Revive & Restore, multiple Audubon societies, the National Wildlife Federation, the American Littoral Society, the American Bird Conservancy, Physicians’ Committee for Responsible Medicine, the Humane Society of the United States and the Humane Society International are among the coalition’s leading partners. Since 2018, the group has led science-based campaigns aimed at halting years of decline in horseshoe crab populations and to fully restore them by 2030.
• The Center for Biological Diversity believes that the welfare of human beings is deeply linked to nature. Because diversity has intrinsic value, and because its loss impoverishes society, the Center works to secure a future for all species, great and small, hovering on the brink of extinction. The Center uses science, law and creative media to protect the lands, waters and climate that species need to survive.

How is information for the Scorecard being gathered?

To better understand the industry’s progress in adopting more sustainable endotoxin testing solutions, we have developed a survey for the 50 largest pharmaceutical companies based on 2023 total revenue. The survey asks company representatives to indicate which provided statements are true about their company’s safety testing methodologies and their plans to transition to using synthetic alternatives.

Each potentially true statement is worth a number of points. A company’s total number of points corresponds to a sustainability rating of 1-5 horseshoe crabs. The more points, the higher the sustainability rating.

In December 2024, the survey was sent to business representatives at the 50 largest pharmaceutical companies in the world. Completed surveys were requested by February 1, 2025. We anticipate that this first survey will initiate an ongoing conversation with the biomedical community as more companies transition to synthetic alternatives for safety testing. 

Results of the surveys will be available on the Scorecard here beginning in February 2025.