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Manufacturing

The Proven Manufacturing Process of CroFab Ensures Only the Most Effective and Highest Quality Venom-Specific Antibodies 

Watch Alex Garrard, Clinical Toxicologist, discuss the manufacturing process for CroFab.

Follow the Manufacturing Process for CroFab


Hold the cursor over highlighted steps of the manufacturing process to learn how CroFab is specifically manufactured to ensure the safe and effective management of envenomation by pit vipers native to the United States.

Steps of the manufacturing process for CroFab

Venom Collection From
Clinically Relevant Native Pit Vipers1

Water Moccasin - Coiled

Cottonmouth/
Water Moccasin

Eastern Diamondback - Coiled

Eastern
Diamondback

Mojave Rattlesnak Coiled

Mojave
Rattlesnake

Western Diamondback - Coiled for Strike

Western
Diamondback

  • The venom of 4 different geographically and clinically relevant North American pit viper species native to the US are separately collected.1,5
  • The venom from each species is used to immunize a separate flock of sheep.1,5

Antibody Collection From Australian Sheep1,2

  • CroFab is manufactured from serum obtained from sheep in Australia, which are free from prion disease and raised within a robust biosecurity system that ensures quality blood-derived products.2
  • Serum from each flock of sheep is separately extracted, allowing the production of antibodies specific to each of the 4 species of pit vipers.1

Removal of FC Fragment to Reduce Hypersensitivity1,3,4

  • Individual antibody fragments are cleaved from the Fc portion, which may cause allergic reactions if not discarded, yielding a small venom-specific protein (Fab) fragment (50 kDa).1,3,4

Affinity Purification to Increase Specificity and Reduce Adverse Reactions1,2

  • A separate affinity purification process eliminates nonspecific antibodies, increasing the purity of the Fab fragments.1,2
  • Each of the 4 monospecific antivenoms undergo 2 separate validated viral inactivation and clearance steps to ensure that the product is free from viruses.2
CroFab vial


Four monospecific antivenoms are
combined to become CroFab. 

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CroFab safety is backed by more than 20 years of clinical experience 

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CroFab is clinically proven to achieve initial control of envenomation 

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IgG antibody icon

CroFab rapidly binds to and neutralizes venom toxins 

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References

  1. CroFab®. Prescribing information. BTG International Inc.; August 2018.

  2. Data on file. BTG International Inc.

  3. Alvarenga LM, Zahid M, di Tommaso A, et al. Engineering venom’s toxin-neutralizing antibody fragments and its therapeutic potential. Toxins. 2014;6(8):2541-2567.

  4. Laustsen AH, María Gutiérrez J, Knudsen C, et al. Pros and cons of different therapeutic antibody formats for recombinant antivenom development. Toxicon. 2018;146:151-175.

  5. WHO Expert Committee on Biological Standardization. WHO Technical Report Series, No. 1004, Annex 5; 2017. Accessed June 13, 2022. https://cdn.who.int/media/docs/default-source/biologicals/blood-products/document-migration/antivenomglrevwho_trs_1004_web_annex_5.pdf?sfvrsn=ef4b2aa5_3&download=true

Indication and Important Safety Information
Indication

CroFab® Crotalidae Polyvalent Immune Fab (Ovine) is a sheep-derived antivenin indicated for the management of adult and pediatric patients with North American crotalid envenomation. The term crotalid is used to describe the Crotalinae subfamily (formerly known as Crotalidae) of venomous snakes which includes rattlesnakes, copperheads and cottonmouths/water moccasins.

Important Safety Information
Contraindications

Do not administer CroFab® to patients with a known history of hypersensitivity to any of its components, or to papaya or papain unless the benefits outweigh the risks and appropriate management for anaphylactic reactions is readily available.

Warnings and Precautions

Coagulopathy: In clinical trials, recurrent coagulopathy (the return of a coagulation abnormality after it has been successfully treated with antivenin), characterized by decreased fibrinogen, decreased platelets, and elevated prothrombin time, occurred in approximately half of the patients studied; one patient required re-hospitalization and additional antivenin administration. Recurrent coagulopathy may persist for 1 to 2 weeks or more. Patients who experience coagulopathy due to snakebite should be monitored for recurrent coagulopathy for up to 1 week or longer. During this period, the physician should carefully assess the need for re-treatment with CroFab® and use of any type of anticoagulant or anti-platelet drug.

Hypersensitivity Reactions: Severe hypersensitivity reactions may occur with CroFab®. In case of acute hypersensitivity reactions, including anaphylaxis and anaphylactoid reactions, discontinue infusion and institute appropriate emergency treatment. Patients allergic to papain, chymopapain, other papaya extracts, or the pineapple enzyme bromelain may also have an allergic reaction to CroFab®. Follow-up all patients for signs and symptoms of delayed allergic reactions or serum sickness (e.g., rash, fever, myalgia, arthralgia).

Adverse Reactions

The most common adverse reactions (incidence ≥ 5% of subjects) reported in the clinical studies were urticaria, rash, nausea, pruritus and back pain. Adverse reactions involving the skin and appendages (primarily rash, urticaria, and pruritus) were reported in 12 of the 42 patients. Two patients had a severe allergic reaction (severe hives and a severe rash and pruritus) following treatment and one patient discontinued CroFab® due to an allergic reaction. Recurrent coagulopathy due to envenomation and requiring additional treatment may occur.

Please see full Prescribing Information.