Chemical Inactivation of Whole Tissue or Homogenized Tissue
Date: February 13, 2018
Subject: FSAP Policy Statement: Chemical inactivation of whole tissue or homogenized tissue
The Federal Select Agent Program (FSAP) is a collaboration between the Centers for Disease Control and Prevention (CDC), Division of Select Agents and Toxins (DSAT) and the Animal and Plant Health Inspection Service (APHIS) Division of Agricultural Select Agents and Toxins (DASAT) to regulate the possession, use, and transfer of biological agents and toxins listed in 7 C.F.R. Part 331, 9 C.F.R. Part 121, and 42 C.F.R. Part 73 (select agents and toxins). The FSAP administers the select agent and toxin regulations in close coordination with the Federal Bureau of Investigation’s Criminal Justice Information Services Division (CJIS).
In meeting the in-house validation/verification of inactivation by chemical inactivation of whole tissue or homogenized tissue, it is FSAP policy to allow entities to select one tissue type (either (1) the tissue that is expected to have the highest concentration of the specific agent to be inactivated or (2) determine agent concentration for the agent to be inactivated in a tissue before performing inactivation to use as the maximum limit for that agent) to serve as a surrogate for other tissues, including those in other animal models, so long as all standardized conditions are held constant such as the agent used, tissue size, and ratio of tissue to volume of inactivating chemical. A safety margin must be incorporated into the final chemical inactivation procedure to ensure the effective inactivation of the agent.
For example, if the spleen contains the largest amount of viable select agent after exposure, the spleen can be selected as the tissue used to validate the inactivation procedure. Once the validation has occurred and a safety margin added to the inactivation procedure, the procedure can be used for any other tissue in any other animal model so long as all standardized conditions are held constant.
If the entity does not know which tissue, or does not want to select the tissue that would have the highest concentration of the specific agent, the entity should determine the agent concentration in a tissue (for example, the amount of specific agent per gram of tissue) and the procedure must be validated for that concentration and a safety margin needs to be incorporated into the final chemical inactivation procedure. Once the validation has occurred the inactivation procedure can be used for any other tissue from any other animal model so long as all standardized conditions are held constant.
This policy statement is effective February 13, 2018.
For more information on inactivation, please see the guidance at https://www.selectagents.gov/irg-intro.html.
For biological agents and toxins determined by HHS to have the potential to pose a severe threat to public health and safety (select agents and toxins), the Public Health Security and Bioterrorism Preparedness and Response Act of 2002 (42 U.S.C. 262a) directs the promulgation of regulations to establish and enforce safety procedures for the possession and use of select agents and toxins, including measures to ensure proper training and appropriate skills to handle such agents and toxins. 42 U.S.C. § 262a(c)
For biological agents and toxins determined by USDA to have the potential to pose a severe threat to animal health or animal products (select agents and toxins), the Agricultural Bioterrorism Protection Act of 2002 (7 U.S.C. 8401) directs the promulgation of regulations to establish and enforce safety procedures for the possession and use of such select agents and toxins, including measures to ensure proper training and appropriate skills to handle such select agents and toxins. 7 U.S.C. 8401(c)
Zoonotic select agents and toxins are regulated by both HHS and USDA. See 42 C.F.R. § 73.4 and 9 C.F.R. § 121.4.
Federal regulations include provisions regarding select agents that are excluded from the requirements of the select agent regulations. Specifically, a select agent or regulated nucleic acids that can produce infectious forms of any select agent virus that has been subjected to a validated inactivation procedure that is confirmed through a viability testing protocol is excluded from the requirements of the select agent regulations. Surrogate strains that are known to possess equivalent properties with respect to inactivation can be used to validate an inactivation procedure; however, if there are known strain-to-strain variations in the resistance of a select agent to an inactivation procedure, then an inactivation procedure validated on a lesser resistant strain must also be validated on the more resistant strains.
See 42 C.F.R. §§ 73.3(d)(4), 73.4(d)(4), 9 C.F.R. §§ 121.3(d)(4), 121.4(d)(4), 7 C.F.R. §331.3(d)(4).
This policy statement will be provided to the Responsible Official via SA Gram for each registered entity on or before the effective date; and to the Responsible Official for each newly registered entity during the registration process. A copy of this policy statement may also be found at http://www.selectagents.gov.