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
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
Immunization of Sheep in Australia2
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)
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
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
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- 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
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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
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Viral clearance provides an extra layer of security to ensure product is free from viruses2
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- Two validated independent virus inactivation steps for extra assurance
- Includes both viral filtration and low pH hold steps
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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.