Guidance on the Inactivation or Removal of Select Agents and Toxins for Future Use: Inactivation
Historical inactivation failures by registered entities required the Federal Select Agent Program (FSAP) to focus on ways to increase the certainty that inactivated select agents and regulated nucleic acids intended for further use do not contain live agent. This is particularly important when the inactivation procedures are tempered in order to avoid disrupting the physical characteristics of the agent or toxin. FSAP acknowledges that 100% inactivation of material is not possible in both a mathematical and practical sense. However, FSAP expects the risk of live agent or toxin in inactivated material to be as low as possible given the intended use of the material and the consequences of inactivation failures.
Inactivation procedures used to render a select agent nonviable, regulated nucleic acids non-infectious, or select toxins non-toxic may fall into the following categories: physical (e.g. heat or irradiation), enzymatic (e.g. lysozyme), or chemical. Filtration procedures can be used to remove viable select agents from biological fluids, culture supernatant, and other materials.
For a select agent or regulated nucleic acids to be properly characterized as non-viable after treatment, the agent must not have the ability to grow or replicate, and the toxin must not have the ability to cause toxicity. Exposure to the agent, toxin, or nucleic acids must not result in infection or toxicity.
Select Agent or Regulated Nucleic Acid Inactivation
Select agents or regulated nucleic acids are considered non-viable or non-infectious only after being subjected to an in-house validated inactivation procedure that is confirmed through a viability or infectivity testing protocol. The responsibility of assuring non-viability or non-infectivity, remains on the individual or entity possessing the select agent or regulated nucleic acids.
An entity must use a validated inactivation procedure to render a select agent non-viable or regulated nucleic acids non-infectious. This means that the inactivation procedure’s efficacy must be confirmed by data generated from a viability testing protocol to render a select agent non-viable for future use. It also means the procedure that renders nucleic acids that can produce infectious forms of select agent virus non-infectious for future use. Validation of an inactivation procedure that renders a select agent non-viable or regulated nucleic acids non-infectious may include:
- Use of the exact conditions of a commonly accepted procedure (such as autoclaving) whose efficacy is confirmed by data generated in-house by the entity using a viability testing protocol.
- Use of a published procedure with adherence to the exact published conditions whose efficacy is confirmed by data generated in-house by the entity using a viability testing protocol.
- Use of entity derived procedure with specific conditions whose efficacy is confirmed by data generated in-house by the entity using a viability testing protocol.
Select Toxin Inactivation
The new inactivation provisions apply to select agents and regulated nucleic acids only. For a select toxin to be considered non-toxic and therefore excluded from the regulations, a validated inactivation procedure should be used but validation does not have to occur in-house and the inactivation provisions found in the records and RO section do not apply. The difference in validation requirements for toxins is due to the non-replicating nature of toxins.
Nonregistered clinical or diagnostic laboratories and other entities that possess, use, or transfer a select agent or toxin that is contained in a specimen presented for diagnosis or verification are exempt from the inactivation requirements, so long as they meet the requirements found in 7 CFR §331.5(a), 9 CFR §§121.5(a), 121.6(a), 42 CFR §§73.5(a), 73.6(a).