Exclusion Guidance Document: Requests for Exclusion of Attenuated Strains or Toxins Modified to be Less Potent or Toxic

The HHS Secretary or APHIS Administrator will grant or deny the request for reconsideration as promptly as circumstances allow and will state, in writing, the reasons for the decision.

If an excluded attenuated strain or modified toxin is subjected to any manipulation that restores or enhances its virulence or toxic activity, the resulting select agent or toxin will be subject to the select agent regulations.

Review of Exclusion Requests

FSAP reviews requests for exclusions and may seek input from CDC’S Intragovernmental Select Agents and Toxins Technical Advisory Committee (ISATTAC), which is comprised of federal government subject matter experts from HHS, USDA, the Department of Homeland Security, and the Department of Defense. ISATTAC reviews requests for the exclusion of attenuated strains and modified toxins of HHS only or overlap select agents and toxins. For VS only agents, federal subject matter experts from APHIS, ARS, and CVB will review the request.

Some of the criteria used to determine if a strain or toxin should be excluded are given below. The entities request should contain the following:

1. Documented history of not causing disease in humans, or relevant animal or plant models.
2. Defined genetic mutations or alterations known to attenuate virulence in humans or relevant animal or plant models.
3. Data showing the mutations have a low frequency of reversion to wild-type virulence.
4. Level of difficulty in engineering the attenuated strain to restore wild-type virulence. For each pathogen, the sample size and type of animal or plant model used to test virulence is important.
5. Quantitative measures demonstrating a change in virulence in an appropriate animal or plant model.
6. Information regarding tests that may be conducted to differentiate animals or plants exposed to the attenuated strain from those infected with the wild-type organism.
7. Related published scientific papers supporting the methods and data provided for the exclusion.

See the data requirements necessary for consideration of an exclusion request for highly pathogenic Avian influenza (HPAI) virus pdf icon[PDF – 243 KB] on the FSAP website.

Request to Appeal a Decision Denying an Exclusion Request

An individual or entity may make a written request to the HHS Secretary or APHIS Administrator for reconsideration of a decision denying an exclusion application. The written request for reconsideration must state the facts and reasoning upon which the individual or entity believes the decision was incorrect. FSAP will grant or deny the request for reconsideration as promptly as circumstances allow and will state, in writing, the reasons for the decision. You may submit the written request to FSAP through eFSAP for registered entities or email lrsat@cdc.gov or DASAT@usda.gov for non-registered entities.