The US Food and Drug Administration (FDA) has finalized guidance detailing the types of data and study considerations necessary to support the approval of diagnostics intended to measure levels of unintended radiation exposure in patients.
Unlike physical dosimetry devices, which measure the actual dose of radiation delivered to a patient, the guidance deals with biodosimetry devices, which measure a patient's physiological, biological or chemical response to radiation. FDA says this gives biodosimetry devices an advantage in determining treatment and outcomes versus physical dosimeters, as they are able to take into account differences in patients' radiation sensitivity.
The devices may act as medical countermeasures for a mass radiation exposure event, such as a nuclear attack or natural disaster affecting a nuclear power plant, according to FDA.
The final guidance is largely similar to the draft version from 2014, though a number of sections have been reformatted.
FDA says that biodosimetry devices present "unique challenges" due to the limits of how they may be studied in premarket settings.
"For example, ethical considerations limit the availability of appropriate clinical samples for biodosimetry device performance studies, leading to the expected use of animal models as surrogates for clinical validation purposes," FDA writes.
FDA says the greatest risk to patients is if the devices' results are inaccurate. The agency warns that a false positive could cause patients to undergo unnecessary treatment for acute radiation syndrome (ARS), while a false negative could result in patient injury or death due to inadequate treatment.
However, the agency says it may consider approving less accurate biodosimetry devices if they are able to provide more rapid results, as current methods detecting absorbed radiation can take several days.
Because this type of device is relatively new, FDA encourages sponsors to go through the agency's pre-submission program to get input on developing their product.
In describing the qualities of a biodosimetry device, FDA says sponsors should specify the type of analyte the test uses, such as DNA, RNA or protein; the types of specimen it is designed to analyze, such as blood, urine or saliva; and the populations it is intended for. In a change from the draft version of the guidance, FDA is also asking sponsors to detail the intended use setting(s) for the device.
FDA says sponsors should discuss what stages of a response the device is intended for, i.e. early field triage or subsequent clinical evaluation and confirmatory testing. Additionally, the agency says it expects sponsors to consider the appropriate timeframe the device should be used in, and any limitations of the device that may affect the validity of its results.
Animal and Human Studies
While animal studies are typically not used to support the approval of diagnostics, FDA says they may be necessary "to supplement human clinical samples to demonstrate device performance."
Notably, the agency says this recommendation is limited only to biodosimetry devices, and "is not applicable to the Animal Rule pathway for approval of drugs or biological products."
For FDA to consider using animal model data, the agency says sponsors must meet certain criteria:
- "The analyte(s) being detected is not stable in archived specimens;
- A diligent search of available specimen banks has failed to yield adequate samples for testing; or
- A prospective study is either unethical, or prospective studies that may be ethically performed will not yield a sample set adequate to demonstrate assay performance over the measuring interval of the device."
However, the agency says it still expects sponsors to conduct appropriately designed pivotal studies using human samples in order to demonstrate the performance of a biodosimetry device. These studies can either be prospective studies involving patients who have been dosed with radiation as part of a therapeutic intervention, or using human tissue samples.