CroFab® [Crotalidae Polyvalent Immune Fab (Ovine)] is a sterile, nonpyrogenic, purified, lyophilized preparation of ovine Fab (monovalent) immunoglobulin fragments obtained from the blood of healthy sheep flocks immunized with one of the following North American snake venoms: Crotalus atrox (Western Diamondback rattlesnake), Crotalus adamanteus (Eastern Diamondback rattlesnake), Crotalus scutulatus (Mojave rattlesnake), and Agkistrodon piscivorus (Cottonmouth or Water Moccasin). To obtain the final antivenin product, the four different monospecific antivenins are mixed. Each monospecific antivenin is prepared by fractionating the immunoglobulin from the ovine serum, digesting it with papain, and isolating the venom-specific Fab fragments on ion exchange and affinity chromatography columns.

CroFab (crotalidae polyvalent immune fab ovine) is standardized by its ability to neutralize the lethal action of each of the four venom immunogens following intravenous injection in mice. The potency of the product will vary from batch to batch; however, a minimum number of mouse LD50 neutralizing units against each of the four venoms is included in every vial of final product, as shown in Table 1. For comparison, the minimum potency of each monospecific component in the batches demonstrated to be efficacious in clinical trials is also included in Table 1.

Table 1. Minimum Mouse LD50 Neutralizing Units* for Each Venom Component

Venom Minimum Potency per Vial of CroFab Minimum Potency per Vial of Clinical Trial Batches
[95% Reference Interval]
Crotalus atrox 1350 935
[760 - 1200]
Crotalus adamanteus 800 1805
[1320 - 2250]
Crotalus scutulatus 5210 11630
[8000 - 17860]
Agkistrodon piscivorus 460 755
[580 - 980]
* One neutralizing unit is determined as the amount of the mixed monospecific Fab proteins necessary to neutralize one LD50 of each of the four venoms, where the LD50 is the amount of venom that would be lethal in 50% of mice.

Each vial of CroFab (crotalidae polyvalent immune fab ovine) contains up to 1 g of total protein and sodium phosphate buffer consisting of dibasic sodium phosphate USP and sodium chloride USP. Thimerosal is used as a preservative in the manufacturing process, and as such, mercury is carried over into the final product at an amount no greater than 104.5 mcg per vial, which amounts to no more than 1.9 mg of mercury per dose (based on the maximum dose of 18 vials used in clinical studies of CroFab (crotalidae polyvalent immune fab ovine) ). The product is intended for intravenous administration after reconstitution with 10 mL of Sterile Water for Injection USP.

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