While exceedingly rare, radiological disasters — including the detonation of an improvised nuclear devices or a nuclear meltdown — do occur. To that end, the FDA has unveiled final guidance intended to help devicemakers develop products to help in mass casualty situations.
Dated April 18, a new guidance document applies to medical device systems that aim to measure biological responses to radiation absorption. It finalizes a draft guidance released Dec. 30, 2014; however, it isn’t intended for radiation doses used in the course of therapy.
While not providing specific study designs, the guidance gives an overview of the principles for studies to establish “reasonable assurance of the safety and effectiveness of biodosimetry devices.” As the document notes, incorrect use of these devices could lead to inappropriate treatment for either a false positive reading or an overestimation of absorption.
Because existing methods to determine absorbed radiation take days to complete, the FDA is aiming to cut the amount of time it takes to develop a treatment strategy to patients.
To that end, sponsors should develop a validation plan to back up claims in the device’s intended use statement and discuss their plans with the FDA before beginning their studies.
The agency up front acknowledges that it will be impossible to validate these devices before marketing them; therefore, they should include in their PMA submission a plan to conduct postmarket testing in the event of a real-world situation.
Unlike the draft guidance, the final document addresses the benefit of biodosimetry over physical dosimetry, which is more appropriate for measuring the actual radiation dose delivered. Biodosimetry, on the other hand, “takes into account the natural patient biological variability in radiation response,” according to the document. That can prove helpful in differentiating between a patient who is radiation sensitive and one who is resistant.
Intended Use Statement
The final guidance also provides an overview of what an intended use statement should specify. It includes three items from the draft version ― the nature of the analyte, specimen types for testing, for example, blood, urine or saliva, and the specific patient population ― and adds a fourth: intended use setting.
In addition, the statement should include stage of response ― that is, early field triage or during clinical evaluation. For the latter, “specific clinical indicators of health status should be part of the intended use statement,” according to the document.
The statement also should address appropriate timeframes for testing and potential limitations, such as validation testing not being conducted in certain patient populations.
Sampling, Other Considerations
The document acknowledges that samples may be difficult to obtain during device validation. To address this problem, the agency says sponsors may use contrived samples ― which are designed to mimic a patient sample ― as a supplement to clinical samples. Examples include ex vivo irradiation of the appropriate matrix, spiking the analyte of interest into the appropriate matrix or using animal-derived specimens.
Other topics covered in the final document include instrumentation and software, animal study considerations, labeling and CLIA categorization.
Read the guidance here: www.fdanews.com/04-18-16-guidance.pdf. — Elizabeth Hollis