For decades, drug companies have depended on a component in the blood of the horseshoe crab to test injectable medicines, including vaccines, for dangerous bacterial contaminants called endotoxins.
Conservationists and some businesses have pushed for wide acceptance of an alternative test, to protect the horseshoe crabs and birds that feed on their eggs. Earlier this year, these people seemed to be on the brink of success as the nongovernmental group that issues quality standards for such tests moved toward putting the alternative test on the same footing.
The debate has been widely monitored as demand has grown for testing new vaccines against the coronavirus. Billions of vaccine doses would eventually require endotoxin testing.
Endotoxins are molecules in the cell walls of many common bacteria. E. coli is one, salmonella another. The toxins can cause fever and death in humans even if the bacteria that produced them have been killed. Toxic shock syndrome is caused by endotoxins.
Pharmaceutical companies must make sure the toxins are not present in any injectable drugs they make. Ingredients, like water, must be tested at each step of the manufacturing process, as well as in the final product.
“It is crazy making that we are going to rely on a wild animal extract during a global pandemic,” Ryan Phelan, the head of the nonprofit Revive and Restore, said before the recent decision. Her group supports technological solutions to conservation problems, including replacing the test that uses a component of horseshoe crab blood, called LAL, with a test that uses rFC. It is the synthetic equivalent of a chemical in the crab blood, produced by inserting genes for its creation into microorganisms grown in the lab.
The billions of doses of candidate vaccines, and many of the ingredients at many steps in the production process will all have to undergo endotoxin testing. But companies that produce LAL from horseshoe crab blood say that the supply is adequate.
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Blood extraction from horseshoe crabs at a Lonza biotech facility in Maryland.Credit…Reuters
Lonza AG, a multinational biotechnology company, sells both tests. Also, Lonza recently struck a deal with Moderna to produce a much publicized vaccine candidate for Covid-19. Lonza said in a statement that five billion doses of vaccine would require “less than a day’s combined production for all three LAL manufacturers in the United States.” The three manufacturers are Lonza, Charles River and Associates of Cape Cod. They all argue that the supply of crabs is more than adequate and current production could handle the vaccine surge without difficulty.
Ms. Phelan said this calculation “boggles the mind” because, “for every dose going out the door — each manufacturer will use 10 times the amount of LAL to test every step along the way in the process.” That includes vials, stoppers and other ingredients in the vaccines. In addition, Ms. Phelan said there are likely to be numerous companies producing vaccines in the test phase and along the way.
The rFC test is allowed by the Food and Drug Administration, which is the governmental agency that rules on the safety of drugs, but companies must do more work for their F.D.A. submissions than if they were to use the standard test.
The F.D.A. relies both on work done by manufacturers and on the standards set by the U. S. Pharmacopeia. If a company uses rFC, it must demonstrate to the F.D.A. that, for each new drug, rFC is as effective as the standard LAL test.
The U.S. Pharmacopeia also announced that it would provide some additional information for any vaccine makers to assist them in doing the tests to validate rFC. Revive and Restore had been asking for some form of emergency authorization for use of rFC, given the stress of potential vaccine production.
One company that is turning to the new test in a big way is Eli Lilly, which also pushed for broader approval of the new test.
Jay Bolden, a biologist with Eli Lilly, said the company had been looking at rFC testing since 2015 for several reasons, including a consistent quality of a lab product, a supply that doesn’t depend on an animal population, a company commitment to replace animal use when possible and a reduction in costs.
A red knot, a type of migratory shorebird that feeds on horseshoe crab eggs, was weighed, measured and tagged by a team of researchers and volunteers at Reeds Beach in New Jersey last year.Credit…Michelle Gustafson for The New York Times
On Monday, Mr. Bolden expressed disappointment with the Pharmacopeia decision. “It probably looks like a three-to-four year delay with no guarantee,” he said, that rFC would be considered equivalent to the LAL test.
Rob Anderson, the vice president of global communications at the U. S. Pharmacopeia, said that more evidence is needed to show the equivalence between the two tests because of the many years of data on LAL and a lack of data on rFC.
Frequently Asked Questions and Advice
Updated June 2, 2020
Will protests set off a second viral wave of coronavirus?
Mass protests against police brutality that have brought thousands of people onto the streets in cities across America are raising the specter of new coronavirus outbreaks, prompting political leaders, physicians and public health experts to warn that the crowds could cause a surge in cases. While many political leaders affirmed the right of protesters to express themselves, they urged the demonstrators to wear face masks and maintain social distancing, both to protect themselves and to prevent further community spread of the virus. Some infectious disease experts were reassured by the fact that the protests were held outdoors, saying the open air settings could mitigate the risk of transmission.
How do we start exercising again without hurting ourselves after months of lockdown?
Exercise researchers and physicians have some blunt advice for those of us aiming to return to regular exercise now: Start slowly and then rev up your workouts, also slowly. American adults tended to be about 12 percent less active after the stay-at-home mandates began in March than they were in January. But there are steps you can take to ease your way back into regular exercise safely. First, “start at no more than 50 percent of the exercise you were doing before Covid,” says Dr. Monica Rho, the chief of musculoskeletal medicine at the Shirley Ryan AbilityLab in Chicago. Thread in some preparatory squats, too, she advises. “When you haven’t been exercising, you lose muscle mass.” Expect some muscle twinges after these preliminary, post-lockdown sessions, especially a day or two later. But sudden or increasing pain during exercise is a clarion call to stop and return home.
My state is reopening. Is it safe to go out?
States are reopening bit by bit. This means that more public spaces are available for use and more and more businesses are being allowed to open again. The federal government is largely leaving the decision up to states, and some state leaders are leaving the decision up to local authorities. Even if you aren’t being told to stay at home, it’s still a good idea to limit trips outside and your interaction with other people.
What’s the risk of catching coronavirus from a surface?
Touching contaminated objects and then infecting ourselves with the germs is not typically how the virus spreads. But it can happen. A number of studies of flu, rhinovirus, coronavirus and other microbes have shown that respiratory illnesses, including the new coronavirus, can spread by touching contaminated surfaces, particularly in places like day care centers, offices and hospitals. But a long chain of events has to happen for the disease to spread that way. The best way to protect yourself from coronavirus — whether it’s surface transmission or close human contact — is still social distancing, washing your hands, not touching your face and wearing masks.
What are the symptoms of coronavirus?
Common symptoms include fever, a dry cough, fatigue and difficulty breathing or shortness of breath. Some of these symptoms overlap with those of the flu, making detection difficult, but runny noses and stuffy sinuses are less common. The C.D.C. has also added chills, muscle pain, sore throat, headache and a new loss of the sense of taste or smell as symptoms to look out for. Most people fall ill five to seven days after exposure, but symptoms may appear in as few as two days or as many as 14 days.
How can I protect myself while flying?
If air travel is unavoidable, there are some steps you can take to protect yourself. Most important: Wash your hands often, and stop touching your face. If possible, choose a window seat. A study from Emory University found that during flu season, the safest place to sit on a plane is by a window, as people sitting in window seats had less contact with potentially sick people. Disinfect hard surfaces. When you get to your seat and your hands are clean, use disinfecting wipes to clean the hard surfaces at your seat like the head and arm rest, the seatbelt buckle, the remote, screen, seat back pocket and the tray table. If the seat is hard and nonporous or leather or pleather, you can wipe that down, too. (Using wipes on upholstered seats could lead to a wet seat and spreading of germs rather than killing them.)
How many people have lost their jobs due to coronavirus in the U.S.?
More than 40 million people — the equivalent of 1 in 4 U.S. workers — have filed for unemployment benefits since the pandemic took hold. One in five who were working in February reported losing a job or being furloughed in March or the beginning of April, data from a Federal Reserve survey released on May 14 showed, and that pain was highly concentrated among low earners. Fully 39 percent of former workers living in a household earning $40,000 or less lost work, compared with 13 percent in those making more than $100,000, a Fed official said.
Should I wear a mask?
The C.D.C. has recommended that all Americans wear cloth masks if they go out in public. This is a shift in federal guidance reflecting new concerns that the coronavirus is being spread by infected people who have no symptoms. Until now, the C.D.C., like the W.H.O., has advised that ordinary people don’t need to wear masks unless they are sick and coughing. Part of the reason was to preserve medical-grade masks for health care workers who desperately need them at a time when they are in continuously short supply. Masks don’t replace hand washing and social distancing.
What should I do if I feel sick?
If you’ve been exposed to the coronavirus or think you have, and have a fever or symptoms like a cough or difficulty breathing, call a doctor. They should give you advice on whether you should be tested, how to get tested, and how to seek medical treatment without potentially infecting or exposing others.
Fouad Atouf, the vice president of global biologics for the rFC, said the reason for caution was that “we are dealing with a safety test.” And more evidence was needed on rFC.
“We’re working to build that evidence base and data,” Mr. Anderson said, “But we can’t put a time on that.”
Dr. Bolden, at Eli Lilly, said that given the delays his company will continue using rFC but follow a different path in submissions to the F.D.A.
“We’ll just start using the European test chapter,” he said, referring to the European pharmacopeia’s inclusion of rFC, which “goes live July 1.” He said the company had reason to believe the F.D.A. would accept the information from the European group, which would, essentially, put the alternative test and the traditional one “on an even playing field.”
