Manufacturing

CroFab® Is Produced With Purity, Precision, and Purpose

CroFab® is a sterile, nonpyrogenic, purified, lyophilized preparation of ovine Fab immunoglobulin fragments approved for the management of North American pit viper envenomation in adults and pediatrics.1,2
 

Watch Alex Gerrard, Clinical Toxicologist and Medical Science Liaison, discuss the manufacturing process for CroFab®

 

 

An International Process

Click on each step to learn more

Step 1: Venom Collection in the US: Four US snake venoms used as immunogen to create comprehensive coverage of all US pit viper bites1

Step 2: Bioprocessing in the UK: Bioprocessing, production, and quality control testing of venom immunogens with robust regulatory oversight2

Step 3: Immunization of Sheep in Australia: Four separate flocks of Australian sheep are each immunized with one of the venom types2

Step 4: Fab Creation in the UK: Eliminates risk of cross-linking antigen and formation of immune complexes2

Step 5: Affinity Purification in the UK: Increases specificity and minimizes nonspecific foreign proteins that can lead to adverse reactions2

Step 6: Viral Clearance in the UK: Provides extra layer of security to ensure product is free from viruses2

Step 7: Final Packaging in the US: CroFab® is lyophilized (freeze dried) into a powder and packaged for distribution2

Venom Collection, Testing, and Certification

 
Map of US with text: Venoms from 4 different types of pit vipers native to the United States are separately collected<sup>1</sup>
photo of western diamondback  
photo of Mojave rattlesnake  
photo of eastern diamondback  
photo of water moccasin/cottonmouth  


A process with purpose

The 4 snake types were specifically selected based on key criteria2:

  • Clinical significance
  • Diverse geographic range
  • Broad spectrum of venom toxins
  • Comprehensive coverage of all US pit viper bites
 

Did You Know?


CroFab® demonstrated cross-reactivity with 10 clinically important North American crotalid snake venoms in an animal model.2 

 


Watch Dr. Jami Johnson discuss how CroFab® gives the best coverage against all North American pit viper envenomations.


Immunization of Sheep in Australia2

 
Image of 4 sheep

Four separate flocks of sheep are each immunized with one of the venom types

  • Australian sheep: a host animal from a country that has negligible prion disease
  • Dedicated flocks per venom type guarantee representation of each venom in every vial of CroFab®
  • Immunization of sheep with small and relatively infrequent doses of venom was proven to elicit high levels of specific antibodies
 

Australia has one of the most robust biosecurity systems in the world2

  • High standards of animal welfare
  • High level of biosecurity, ensuring quality blood-derived products
  • Intensive health screening program for donor sheep
  • Sites regulated and inspected by both the Therapeutic Goods Administration (TGA) and Australian Quarantine and Inspection Service (AQIS)
: Graphic of the outline of Australia with padlock icon


 

Did You Know?

In order to protect humans from exposure to unnecessary pathogens, CroFab® is manufactured from serum obtained only from sheep located in Australia.2

Dr. Johnson explains how CroFab® is manufactured using the venom of 4 types of poisonous snakes to create the best antivenom coverage.


Fab Creation in the UK

Serum is collected and transported back to the BTG production facility in Wales2

CroFab® is specifically designed as a small protein fragment for rapid and large volume of distribution in the body.2


2 graphics showing the removal of the Fc fragment
  • Antivenom production separates antibodies from serum
  • Papain, a plant-derived enzyme, cleaves the antibodies, thereby producing Fab molecules each capable of binding venom
  • Fab has been shown to have binding capacity for toxins while eliminating risk of cross-linking antigens and formation of immune complexes that can lead to Type III hypersensitivity reactions


Affinity purification in Wales2


Unnecessary antibodies are removed to yield only venom-neutralizing antibodies, resulting in a purified product.2 By isolating these antibodies, affinity purification2:

  • Increases specificity
  • Minimizes nonspecific foreign proteins that can lead to adverse reactions


Viral clearance provides an extra layer of security to ensure product is free from viruses2
 

2.png

 
  • Two validated independent virus inactivation steps for extra assurance
  • Includes both viral filtration and low pH hold steps

Formulation

CroFab® is formulated without the need for added preservatives at any stage of the process or in the final drug product.2
 

Did You Know?

CroFab® is the result of manufacturing 4 separate monospecific antivenoms that are mixed at the end to create an antivenom that is effective against the venoms of all North American pit vipers. Each component “antivenom” uses venom from 1 snake type, 1 flock of sheep, and its own affinity purification column.1,2

Watch video testimonials and review patient case studies.

References:

1. CroFab® [prescribing information]. BTG International Inc; January 2018. 2. Data on file. Conshohocken, PA; BTG International Inc. 2019.