Conservationists are urging the pharmaceutical industry to quickly adopt a testing method they say would be crucial to the development of a COVID-19 vaccine, while protecting horseshoe crabs in Delaware Bay and the ecosystem that depends on them.
The search for a COVID-19 vaccine has given new urgency to the conservation community’s long-running efforts to persuade Big Pharma to test for bacterial contamination in its drugs and vaccines using a synthetic product called recombinant Factor C (rFC). They want the industry to stop using LAL, a clotting agent that’s contained in the blood of horseshoe crabs and obtained by a process that advocates say kills tens of thousands of the crabs every year.
But their campaign was set back in late April when the U.S. Pharmacopeia (USP), a body that sets professional standards for the industry, delayed a change to its testing protocols that advocates had hoped would allow more pharma companies to use the synthetic product rather than the blood-based one.
Increased demand for crab blood?
After years of efforts to curb the harvest of horseshoe crabs in Delaware Bay and other coastal areas, advocates fear that the need to test any COVID-19 vaccine would dramatically increase demand for crab blood. That would have dire consequences for an already diminished species, unless the pharma industry as a whole starts testing with the synthetic alternative soon.
The potentially enormous demand for a vaccine, and the tests needed to ensure its safety, were shown when Johnson & Johnson, one of the world’s biggest pharma companies, said earlier this month that it is preparing for clinical trials of a coronavirus vaccine in September, and aims to deliver 1 billion doses next year.
“There may not be enough horseshoe crabs in the sea to cover the demand that you have for endotoxin tests for a billion doses of the vaccine,” said Chris Earl, a conservationist and former venture capitalist who is an unpaid intermediary between campaigners and industry groups.
Even without a COVID-19 vaccine, continued bleeding of crabs for LAL is preventing the crab population from recovering. It was decimated in the late 1990s and early 2000s by overharvesting for commercial fishery bait and the biomedical industry.
Since then, the crab population has received some protection from an outright ban on the harvest by New Jersey, starting in 2008, and quotas on a male-only crab harvest in the other bay states, set by the Atlantic States Marine Fisheries Commission.
Repercussions across ecosphere
The population has stabilized but advocates say it remains at only a third of its level before the crash starting in the late 1990s, and that threatens the survival of shore birds, particularly the federally threatened red knot, which depend on the crabs’ eggs on Delaware Bay beaches to fuel their long-distance migrations.
Dr. Larry Niles, a wildlife biologist who has led the shorebird count on the New Jersey side of the bay for the past 24 years, said a new vaccine could lead to a renewed decline in crab numbers, with negative consequences for the birds and other marine life that depend on them, unless the industry switches its testing protocol soon.
“We are concerned that there will be extraordinary need for horseshoe crab blood” if a COVID-19 vaccine is found, Niles said. He said it was “irresponsible” of USP to not allow the proposed endorsement to go forward, given that the efficacy of the synthetic drug has already been established. “We expect that there will be a great need for a biochemical to test for contaminants, and it should be the synthetic,” he said.
Niles and David Mizrahi of New Jersey Audubon are leading the newly formed Horseshoe Crab Recovery Coalition, a national nonprofit that aims to restore the crab population by 2030 to levels seen before the overharvest and urges the biomedical industry to end its use of crab blood.
A late change in plans
On April 22, USP said it cancelled a plan to revise one of its standards that would have allowed the synthetic material to be used as an alternative to LAL, citing unspecified “stakeholder feedback.” Instead, it said it will write a new chapter for rFC in its compendium of industry standards, kicking off a process that’s due for completion by May 2022.
The decision dismayed conservationists who had expected USP to endorse rFC as an alternative to LAL, and so provide pharmaceutical companies with an independent scientific endorsement of the synthetic material that would encourage them to switch from the crab-based agent.
Jaap Venema, chief science officer for the Maryland-based organization, said USP recognizes the value of rFC and plans to make the change sought by conservation groups — albeit not at the time advocates had been expecting.
“USP is committed to integrating validated test methods using rFC into the official pharmacopeia,” Venema said in an emailed statement, referring to the publication that sets legally recognized standards for drugs and various therapies.
He said USP has decided to go ahead with the change because it’s supported by “strong data”; addresses ethical considerations about using “animal-derived material”; is a more sustainable source for testing than the crab-based product; and will improve confidence in test results.
Asked whether USP shouldn’t make the change sooner given the urgency of finding a vaccine for COVID-19, Venema said the organization recognizes the importance of the rFC test for researchers seeking a vaccine for COVID-19, and that its scientists are advising on the use of rFC in vaccines and therapies being developed for the virus.
The new chapter in the USP standards will be published in November next year, and will become official in May 2022, he said.
For its part, the U.S. Food and Drug Administration does not regulate tests but requires manufacturers of finished products to show that “in-process manufacturing testing is accurate and that test methods are validated,” the agency said in a statement.
Even though the pharma industry as a whole hasn’t switched to the synthetic testing material, one leading firm, Eli Lilly and Co., has been using it for testing since 2016, said Jay Bolden, associate quality adviser, and a leading proponent for the industry to change its testing protocol.
He said the company had made the switch after determining that rFC was the preferable alternative in terms of quality, cost and reliability of supply, and didn’t raise the ethical concerns of the crab-blood test.
Bolden said that hundreds of compounds are currently being examined for possible COVID-19 vaccines, and many of those would have to be tested for bacteria. He declined to comment on how much more demand that would create for the crab-based product if the pharma industry doesn’t switch to the synthetic alternative but said there’s no doubt it would increase.
“If 300-400 new compounds need to be tested for endotoxins, clearly more test reagents will be needed,” he said.