Guidance on the Inactivation or Removal of Select Agents and Toxins for Future Use: Terminology
The regulatory requirements and this accompanying guidance applies to select agents and regulated nucleic acids that have undergone an inactivation process on or after March 21, 2017 for future use. Inactivated select agents and regulated nucleic acidsare excluded as nonviable.
Term |
Definition by the SAR or within this Guidance |
| Bioburden reduction studies | Studies based on deliberately adding a specific agent (“spiking”) and subsequently measuring the removal or inactivation during inactivation steps. |
| Inactivation | A procedure to render a select agent or regulated nucleic acids as non-viable or a select toxin non-toxic while retaining characteristic(s) of interest for future use. |
| Infectivity Testing | A protocol to confirm the inactivation procedure by demonstrating the nucleic acids are incapable of producing infectious forms of any of the select agent viruses. |
| Limit of detection (LOD)/Limit of quantitation (LOQ) | The smallest concentration of a select agent or toxin that can be reliably detected or measured by an analytical procedure. |
| Kill curve | The results of a dose-response experiment where a select agent is subjected to increasing levels of the inactivating procedure in order to determine the minimum conditions required to render it nonviable. |
| Margin of error | The amount of error allowed for in case of miscalculation or normal variation in a process. |
| Non-infectious nucleic acid | Nucleic acids no longer capable of producing infectious forms of a select agent virus (e.g. regulated positive sense RNA virus genomes like FMDV or EEE). |
| Non-viable select agent | A select agent no longer capable of growing, replicating, infecting, or causing disease. |
| Non-toxic select toxin | A toxin no longer capable of exerting a toxic effect. |
| Safety margin | The treatment amount designed into an inactivation procedure beyond that required to reach LOD/LOQ, intended to reduce the probability of inactivation failure. |
| Sterility assurance level (SAL) | The probability of surviving organisms in material that has been subjected to inactivation. |
| Toxicity Testing | A protocol to confirm the inactivation procedure by demonstrating the select toxins are non-toxic. |
| Validated inactivation procedure | A procedure, whose efficacy is confirmed by data generated from a viability testing protocol, to render a select agent non-viable, but allows the select agent to retain characteristics of interest for future use; or to render any nucleic acids that can produce infectious forms of any select agent virus non-infectious for future use. |
| Verification | Confirmation by an individual or entity that the use by the individual or entity of a validated inactivation or select agent removal procedure will result in an end product that achieves the expected results. |
| Viability testing protocol | A protocol to confirm the validated inactivation procedure by demonstrating the material is free of all viable select agent. |
Page last reviewed: August 19, 2020, 11:45 AM
Content source: Division of Regulatory Science and Compliance