NON-FDA APPROVED ANTIVENOMS RECOMMENDED IN THIS CPG

Following repeated questions to JTS about using non-FDA-approved antivenoms after publication of the Global Snake Envenomation Management CPG (2020), the JTS Working Group consulted with FDA’s Center for Biologics Evaluation and Research (CBER) to provide clarification and guidance regarding the regulatory framework for DoD medical providers, procurement officers, and commanders who need to obtain the foreign antivenoms listed in this CPG.

Snakebite treatment OCONUS requires the use of non-FDA-approved foreign antivenoms through the Biological-Based Investigational New Drug (BB-IND) pathway.

Non-FDA-approved antivenoms are the only options for treating snakebites outside the United States. None of the 26 foreign antivenoms recommended for OCONUS use in this CPG are FDA-approved, and the FDA does not expect or require them to obtain approval because they are indicated for exotic snakes that are not native to the United States. Instead, the FDA provides a specific legal pathway to facilitate lawful importation, storage, and use of these products: the Biological IND (BB-IND) with Expanded Access under 21 CFR 312 Subpart I. The antivenom BB-IND pathway has been utilized for decades by zoos and private snake keepers, allowing U.S. citizens to procure and administer these lifesaving products with required annual reporting.

DoD is already utilizing the BB-IND pathway to support use of foreign antivenoms.

In AFRICOM, INDOPACOM, SOUTHCOM, EUCOM, and part of NORTHCOM (Mexico), first-line therapy for snakebite utilizes non-FDA-approved antivenoms obtained through the BB-IND/Expanded Access program. The Surgeon General-Department of the Army (TSG-DA) holds the BB-INDs for all antivenoms listed in this CPG, and the Defense Health Agency’s Office of Regulated Activities and Force Health Protection (FHP) Division oversees importation, compliance tracking, and regulatory oversight. Logistics and procurement should follow this established pathway to meet the standard of care and JTS Performance Improvement (PI) objectives.

What type of reporting and documentation is required by the FDA for BB-IND?

Antivenoms accessed through BB-IND require annual and case-specific reporting to FDA CBER. Annual reports are filed each year (FDA Form 1571) and detail whether any antivenom was used in the previous 12 months. When a patient is treated, FDA Form 1572 (found on the FDA website: https://www.fda.gov/about-fda-reports-manuals-forms/forms) is submitted in the annual report and a case report is filed as well. As the BB-IND holder for the US military, the ORA, acting on behalf of TSG-DA is responsible for submitting these reports to the FDA. If any antivenom is administered, please contact a Medical Toxicologist via the Advanced Virtual Support for Operational Forces (ADVISOR) teleconsultation service by calling 833-ADVSRLN (833-238-7756)/ DSN: 312-429-9089 and the Toxicologist will assist in ensuring compliance with FDA guidelines for the use of antivenoms with an IND or in submitting an emergency IND number if one does not already exist.

Who should I contact with questions about obtaining antivenom for my local formulary?

Contact Force Health Protection (FHP) with questions regarding antivenom procurement via the FHP 24/7 Emergency Phone: 301-401-2768 or e-mail: usarmy.detrick.medcom-usammda.mbx.force-health-protection@health.mil.

The U.S. Food and Drug Administration (FDA) does not adjudicate nor approve antivenoms required outside the United States. Code of Federal Regulations (CFR) Title 21 Part 312 classifies these pharmaceuticals as Investigational New Drugs (IND). Therefore, sourcing of these antivenoms occurs through alternate pharmaceutical supply chains. Oversight for IND falls under the Department of Health Operational Medical Systems (DHA OPMED) Force Health Protection (FHP) Division (https://dha.mil/Offices-and-Programs/OPMED/FHP) with regulatory support provided by U.S. Army Medical Research and Development Command’s (MRDC) Office or Regulated Activities (ORA). However, the antivenoms will need to be purchased and acquired by the Combatant Command or on the local market by medical personnel. We recommend contacting the appropriate Geographical Combatant Command Surgeon General’s Office to assist in acquiring and stocking antivenom if there is the credible risk of snake envenomation for which the risks and costs of maintaining and storing said antivenom are appropriate. If medical personnel must acquire the appropriate antivenom on the local economy, it is advised that great caution is taken to ensure the antivenom is legitimate, unexpired, and appropriately stored given that selling and marketing of fraudulent antivenom does occur in developing countries.