Restricted Experiments Guidance: Request to Conduct a Restricted Experiment
The entity’s Responsible Official (RO) should submit any request to conduct a restricted experiment through eFSAP. FSAP will review the request. HHS only (42 CFR § 73.3external icon) or overlap (42 CFR § 73.4external icon and 9 CFR § 121.4external icon) select agents may be further reviewed by CDC’s Intragovernmental Select Agents and Toxins Technical Advisory Committee (ISATTAC). VS only agents (9 CFR § 121.3external icon) and PPQ agents (7 CFR § 331.3external icon), may be further reviewed by the Agriculture ISATTAC (Ag-ISATTAC) . The request should not be submitted as part of an amendment to an entity’s registration. Doing so may delay approval of other changes proposed in the amendment while the restricted experiment request is under review. If the restricted experiment is approved, the entity should amend their registration by submitting the appropriate Form 1 sections related to the experiment. When requesting to conduct a restricted experiment, the entity should submit a cover letter (on official entity letterhead) requesting to conduct the experiment along with the following relevant information:
- Synopsis of the proposed experiment(s) and the intended objective(s).
- Description of the nucleic acid insert (if applicable, complete sequence information is not required) and the predicted biological characteristics of the recombinant product.
- Description of the cloning/expression vector.
- Identification and characteristics of the host organism used for molecular cloning (if applicable).
- Description of the methods used for selection (e.g. recombinant or passive selection) to include all potential drug resistant traits (if applicable, including intermediate variants).
- Description of any alternative drug resistance markers that could be used, i.e., to avoid the acquisition of drug resistance that could compromise the use of the drug to control disease agents in humans, veterinary medicine, or agriculture (if applicable). Provide an explanation as to why these alternative marker genes are not being considered.
- Description of biosafety level including facility containment, equipment and special practices to be utilized for the proposed experiment(s).
- Description of the mechanism and specificity of the antimicrobial resistance (antibiotic, antifungal and antiviral resistance) being conferred to include any cross-resistance to other therapeutically useful antimicrobials (if applicable).
- Estimated amount of toxin (recombinant or synthetic) to be produced (if applicable).
- Synopsis of any planned animal or plant experiments (if applicable) or other relevant animal or plant work.
- Scientific references or supporting documentation, particularly with respect to the biosafety aspects of the proposed experimental product.
In addition, FSAP reviews and considers the following criteria when determining if a) gradient selection experiments (in vitro or in vivo) or b) drug efficacy experiments (in vitro or in vivo) with the intention of evaluating any resistant strains that result from failed therapy with drugs that control disease agents in humans, veterinary medicine, or agriculture in select agents meet the definition of a restricted experiment. For these types of experiments, please address the following:
- Whether isolates less susceptible to the drugs that control disease agents in humans, veterinary medicine, or agriculture will be retained.
- Whether drugs that control disease agents in humans, veterinary medicine, or agriculture will be used at therapeutic doses to limit the growth of a less susceptible population.
- Whether the experimental model will exert pressure to create resistant strains.
- Whether agar plates or broth media will be supplemented with drugs that control disease agents in humans, veterinary medicine, or agriculture to determine if resistant isolates were generated.
- Whether purposeful selection for resistant strains will be conducted.