Best Manufacturing Practices

Those who purchase LAL or TAL and all of us who are helped by the blood from horseshoe crabs can and should know how each manufacturer collects and handles the animals that are used in their bleeding facilities.  End-users of horseshoe crab-based endotoxin detection methods, and patients benefitting from them, can help play a role in horseshoe crab conservation by demanding that best practices be used as well as development of methods to reduce or eliminate the need to bleed horseshoe crabs.

Manufacturing of LAL and TAL requires that horseshoe crabs are collected, handled and bled.  Collection, handling and bleeding practices vary from one manufacturer to another, but most agree that some practices are less harmful to the animals than others.

Hand-collection vs. Trawling

Collection practices in the United States include picking up crabs from the beach by hand, hand collecting from shallow water, and trawling for crabs miles off shore with a fishing boat.  Each method has its benefits and disadvantages. Taking crabs at or close to shore may impact spawning activities and/or disrupt nursery grounds.  Trawling uses fishing nets to collect the crabs.  Although not directly impacting spawning, the nets may cause damage to some of the horseshoe crabs and may disrupt their ocean floor habitat.  Debate exists within the community as to which is the best collection practice.

Photos: © Ariane Müller



The Bleeding Process

Best practices for handling the horseshoe crabs through the bleeding process include keeping the crabs cool and moist, pre-screening and not bleeding injured crabs, and separating unbled from bled within the facility to avoid rebleeding. 

Bleeding the horseshoe crab involves bending them at the hinge between the larger (prosoma) and smaller (opisthosoma) sections and placing them in a rack. The best practice is inserting a sterile needle through the membrane in the hinge and allowing blood to flow or drip into the container until the flow stops naturally. Bleeding horseshoe crabs to death is not an acceptable practice in the U.S.

The volume of blood taken is actually quite small, as most of the material in the collection jars is anticoagulant.

Swift Return

Returning horseshoe crabs to the ocean waters from which they were taken within 24 hours is a best practice. Crabs are often marked prior to return in order to identify and avoid collecting them a second time for bleeding within a year. Some manufacturers bleed horseshoe crabs prior to their use as bait.  Debate also exists as to whether or not bleeding bait crabs is a best practice.

As with harvesting, the crabs should be returned to the ocean in a moist, climate-controlled vehicle to reduce stress and they should be returned to their harvesting site.

In the U.S., best manufacturing practices are discussed at meetings held in conjunction with the Atlantic States Marine Fisheries Commission (ASMFC, www.asmfc.org).  The ASMFC and its horseshoe crab management plan and advisory group are working together with the LAL manufacturers to help protect the sustainability of this natural resource.

 

LAL Harvest and Mortality

The LAL producers are currently at the upper limits of their harvesting allocation, based on bleeding mortality. In fact, since 2007, they have exceeded the mortality threshold of 57,500 set down by the ASMFC, based on a calculated mortality rate of 15%. A review process is underway to determine what if anything should be done. Unless the threshold is raised and/or the level of mortality drops, there is not much room for growth, certainly not at the levels projected by the healthcare industry who are dependant upon endotoxin detection.

Up until now, LAL producers have been able to manage growth through improved harvesting, handling and release protocols, as well as advancements in manufacturing and testing methodologies. However, with production waste at a minimum, and testing methodologies already fine tuned, LAL producers will need to harvest more animals in order to keep pace with global demand.

LAL Harvest and Mortality Rates by Year

  2005 2006 2007 2008 2009 2010 2011 2012 2015
Harvested for LAL 323,149 367,914 500,251 511,478 512,552 482,704 628,476 611,827 559,903
Total Mortality 44,830 49,182 63,432 63,285 60,642 75,428 80,827 79,786 70,223

* Harvest numbers include all horseshoe crabs brought to bleeding facilities, including those that were harvested as bait and counted against state quotas. Most of the biomedical crabs harvested are returned to the water after bleeding; a 15% mortality rate is estimated for all bled crabs.

Sustainability and Social Responsibility in Suppliers

A reliable and sustainable supply of raw materials is critical for pharmaceutical and medical device manufacturers to provide their products to patients on time.  Sustainability in a supplier’s ability to provide raw materials is linked to their social and environmental business practices.  Companies that act responsibly with how they treat their employees, how their facilities affect the environment and how they use natural resources are the types of suppliers with whom pharmaceutical and medical device companies should do business.  Many companies have global citizenship, environmental sustainability or similar policies and include them on their websites.

LAL/TAL endotoxin detection kits are critical materials for the pharmaceutical and medical device industries.  Without a reliable and sustainable source of LAL/TAL kits, products, such as injectable pharmaceuticals, cannot be cleared and released for commercial sale.  Understanding how the LAL/TAL manufacturers manage the natural resource horseshoe crab, can help companies choose vendors that act responsibly and can promote the sustainability of the horseshoe crab species.

 

Best Practices in the U.S.

Associates of Cape Cod (division of Seikagaku Corporation, Japan) Charles River Endosafe (division of Charles River Laboratories, USA) Lonza Walkersville (division of Lonza Group, Switzerland) Wako
Chemicals
(division of Wako Pure Chemicals, Japan)
Harvesting: Collection Method trawling:
100%
trawling:
20%
hand harvest:
80%
trawling:
100%
trawling:
100%
Husbandry: Moist and temperature-controlled transport yes:50% yes:100% yes:100% yes:100%
Husbandry: Prescreening for injured crabs yes:100% yes:100% yes:100% yes:100%
Husbandry: Separating crabs to avoid
re-bleeding
yes:100% yes:100% yes:100% yes:100%
Bleeding: Aseptic environment and sterile needle use yes:100% yes:100% yes:100% yes:100%
Release: Returns crabs to point of origin
no, some bled crabs go to secondary market yes:100% yes:100% yes:100%
Release: Return within 24 hours no, see above 100%
in 48 hours
100%
in 48 hours
100%
in 48 hours
Release: Crab tagging prior to return no yes: 50% yes:100% yes: 50%
Regulations: Comply with all government harvesting and conservation requirements yes:100% yes:100% yes:100% yes:100%
Regulations: Comply with ASMFC Best Practices document yes:100% yes:100% yes:100% yes:100%
Disclosure: Company makes HSC use and mortality data public no no no no

 

Best Practices in Asia

Fuzhou Xinbei Biochemical Industrial Seikagaku Corporation (Parent company of Associates of Cape Cod, USA) Xiamen Chinese Horseshoe Crab Reagent Manufactory Zhanjiang A&C Biological (Division of Charles River Laboratories) Zhanjiang Bokang Marine Biological Co. Ltd.
Harvesting: Collection Method trawling:
100%
trawling:
100%
trawling:
100%
trawling:
100%
trawling:
100%
Husbandry: Moist and temperature-controlled transport yes: 40% yes: 40% yes: 40% yes: 40% yes: 40%
Husbandry: Prescreening for injured crabs no no no no no
Husbandry: Separating crabs to avoid re-bleeding no no no no no
Bleeding: Aseptic environment and sterile needle use yes:100% yes:100% yes:100% yes:100% yes:100%
Release: Returns crabs to point of origin no, 100% mortality no, 100% mortality no, 100% mortality no, 100% mortality no, 100% mortality
Release: Return within 24 hours no, 100% mortality no, 100% mortality no, 100% mortality no, 100% mortality no, 100% mortality
Release: Return to point of origin no, 100% mortality no, 100% mortality no, 100% mortality no, 100% mortality no, 100% mortality
Release: Crab tagging prior to return no, 100% mortality no, 100% mortality no, 100% mortality no, 100% mortality no, 100% mortality
Regulations: Comply with all government harvesting and conservation requirements yes:100% yes:100% yes:100% yes:100% yes:100%
Disclosure: Company makes HSC use and mortality data public no no no no no

 

See our list of companies that purchase their endotoxin detection materials from sustainable and responsible manufacturers.

Looking for more on the science? Visit our Research section.