APR Nov/Dec 2022 - 64

VENDOR VIEWPOINT
Endotoxin Testing Considerations -
Reducing LAL Use with
Compendial Methods
Hayden Skalski
Life Sciences Product Application Specialist
Veolia Water Technologies & Solutions,
Sievers Instruments
The link between horseshoe crabs and pharmaceutical and medical device manufacturing
is an important subject today in the biomedical industry - an industry that is prioritizing
sustainability while also ensuring safety and quality of products for patients. The blood from
horseshoe crabs contains factors that are used to manufacture limulus amebocyte lysate (LAL),
a reagent that can test whether drug products or medical devices have been contaminated
with bacterial endotoxin. Through a series of cascade reactions, the crab's blood factors have a
clotting mechanism in place to detect any introduction of bacterial harm. This testing is critical
to detect dangerous - and potentially deadly contaminants - but it puts pressure on horseshoe
crabs and their desired blood.
The Atlantic horseshoe crab, Limulus polyphemus, is a species of marine arthropod found
along the eastern coast of North and Central America. The Delaware Bay supports the largest
spawning population in the world.1
The limulus species is around 450 million years old and is
one of the most studied invertebrates in the world due to its unique blood. Horseshoe crabs
are widely used for a few purposes such as a food source for birds (eggs), bait for commercial
eel and conch fisheries, and the biomedical industry.1
Baiting of horseshoe crabs, particularly
in the Northeast region, is allowed and is seen as the main cause of mortality and declining
population of the Atlantic horseshoe crab species. Atlantic coastwide bait landings in 2020
were reported at 456,675 crabs.1
of horseshoe crabs for any bait use is prohibited through law.2
Hayden Skalski is the Life
Sciences Product Application
Specialist for the Sievers
Instruments product line,
specializing in bacterial endotoxins testing
(BET). Hayden has over 8 years of experience
in the pharmaceutical industry and Quality
Control Microbiology and has presented on
numerous topics surrounding endotoxin
testing. Previously, Hayden held roles at
Charles River Laboratories, Regeneron and
Novartis, validating and executing method
development protocols for endotoxin testing,
providing customer support, troubleshooting
and supporting high-volume product testing.
Hayden has a B.S. from the University at
Albany (SUNY) in Biology.
In the Southeast Atlantic state of South Carolina, harvesting
All fisheries who capture and
collect horseshoe crabs must possess a proper permit for commercial, educational, or private
purposes.2
This law is extremely important to the horseshoe crab population, as it allows
the population to flourish in the southeast and protects the crab species from baiting. As
mentioned previously, a large population of the Atlantic horseshoe crabs is collected for the
biomedical industry to support production of LAL reagent. Blood from the horseshoe crab
is obtained by collecting adults and extracting a portion of their blood. Most crabs collected
and bled by the biomedical industry are, as required by the Fishery Management Plant (FMP),
released alive to the water from where they were collected; however, a portion of these crabs
die from the procedure.1
Per the state compliance reports in 2021, the population of crabs have
a very low mortality rate from biomedical use compared to the main source of mortality which
is baiting. The 2019 Horseshoe Crab Benchmark Stock Assessment evaluated the stock status
of the resource by region, finding populations within the Delaware Bay and Southeast regions
remaining consistently neutral and good, respectively, through time.1
Due to the concerns of crab populations and the dependence on their blood for biomedical
purposes, the awareness of alternative bacterial endotoxin methods has risen as of recent years.
Recombinant Factor C (rFC) and recombinant LAL (rLAL) are two alternative methods which do
not use horseshoe crab blood. rFC is the first clotting enzyme in the horseshoe crab's blood
clotting mechanism, and a clone of this Factor C is used for the rFC method. This alternative
64
American Pharmaceutical Review | November/December 2022
APR Nov/Dec 2022

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