Wednesday, October 02, 2024

Should the pharmaceutical industry be using an alternative to horseshoe crab blood?


By Dr. Tim Sandle
DIGITAL JOURNAL
October 1, 2024



Limulus polyphemus - the Atlantic horseshoe crab, found along the Atlantic coast of the United States and the Southeast Gulf of Mexico. By Breese Greg, U.S. Fish and Wildlife Service, CC 3.0.

Since the 1950s when the bright-blue blood of horseshoe crabs was first discovered as a way to detect bacterial by-products (endotoxin) in injectable medicines countless lives have been saved. However, to produce the reagent, millions of the ocean dwellers, especially in the U.S., have been captured, their blood drained from their hearts and returned to the ocean.

The blood contains a clotting factor that points to the presence of bacterial endotoxins. The activity of fishing and harvesting, due to the fatality rate, has affected horseshoe crab populations and consequently the animals are classified as a threatened or vulnerable species.

Demand for horseshoe crab blood has increased through the years as pharmaceuticals have developed.

Today, following adoption first by the European Union and then, after some delay, by the U.S. it is no longer necessary to use the crabs. This is according to Timothy Cernak, a medicinal chemist at the University of Michigan’s College of Pharmacy.

“It’s beyond time to transition to a sustainable alternative for this critical step in drug- safety testing,” Cernak states in a message passed on to Digital Journal. “The pharmaceutical industry is inviting major risks to the supply chain of lifesaving medicines by relying on the blood of a wild animal.”

Cernak discusses the use of an alternative reagent called ‘recombinant factor C’ (rFC). This is a pharmacopeia approved alternative to crab blood. The reagent, if appropriately validated, offers the same safety testing. Its use protects the horseshow crab, slows environmental damage and brings other benefits such as supply reliability.

According to Tim Sandle, recombinant protein production begins with expression vector engineering and transfection into a host system. This step is followed by the steps of:Cell selection,
Medium selection (defining the essential nutrients required for optimal cell growth and target protein productivity is very important),

Cloning,
Screening,
Evaluation.

The objective of manufacturing is the standardized production of the same rFC protein through the use of bioreactor.

Cernak has called on the pharmaceutical industry to turn to the alternative, which not only would spare the crab population and protect the ecosystem, but create a more reliable, predictable supply chain for the substance needed to test so many medical products for safety.

He visited the Delaware Bay earlier this year to witness the annual migration of migratory shorebirds who stop there to fuel up on horseshoe crab eggs in the middle of a 10,000-mile journey, just one example of an ecosystem at risk.

“The endangered red knot is a small bird that completes one of the longest animal migrations on our planet, from the southern tip of Argentina to breeding grounds in the Arctic and back every year, and the pharmaceutical industry is harming this majestic natural event,” Cernak said.

Cernak and Lawrence Niles of Wildlife Restoration Partnerships have authored an urgent letter published in the science journal Nature, urging the pharmaceutical industry to “embrace this innovation in preclinical research and manufacturing … Companies can safeguard public health, supply chains and the delicate balance of ecosystems.”

In the letter, Cernak and Niles called the U.S. decision to allow companies to fully adopt rFC for endotoxin testing “a pivotal moment in the biomedical industry’s relationship with nature.”

Cernak says it’s a duty and responsibility to rethink the process of using crab blood.


No comments: