A complete detailed guide regarding the levels of unintended radiation exposure in patients is now available and agreed on by the US Food and Drug Administration (FDA). It has been titled ‘Radiation Biodosimetry Medical Countermeasure Devices’ and an electronic copy is available for download on the internet as well. The guidance has particularly been constructed to ensure that the industry and agency staff have the required information needed to support market authorization for radiation biodosimetry medical countermeasure devices and clarity on this issue.
Though it is pretty much an extension of the draft established in the Federal Register on December 30, 2014, and then reopened on May 28, 2015, few changes have been made in some sections regarding the format.
Due to radiation, the cells in our body tend to change resulting in pathological behavior of our biological systems. It is important to immediately monitor any change before major harm takes place. The biodosimetry devices take into account the biological, chemical or physiological response of a patient after they have been exposed to radiation and provide both quantitative outputs as well as qualitative information regarding the actual dose of radiation. It is important to note, however, that this differs from physical dosimetry devices which are concerned with the level of radiation given to a patient during treatment. They are in fact concerned with the radiation that one is exposed to during normal work. This could include early field triage settings (mostly qualitative), patient bedsides and certified clinical laboratories. It can also prove to be extremely useful for accidental exposures such as an earthquake or tsunami resulting in high radiation release. It does not include biological assays such as ingested radioisotopes in sputum or urine but will be a helpful measure for personalized therapeutic responses proving to be highly beneficial for the general public and their health.
The main risk factor is the possibility of an inaccurate reading. A false positive result resulting in heightened estimation of absorption levels in an emergency setting could lead to unnecessary or improper acute radiation syndrome (ARS) treatment, whereas a false negative with an underestimated result could lead to injury or even death due to poor treatment or no treatment at all. Hence, it is extremely vital to recognize the risk factors along with the importance of biodosimetric devices.
The draft has been divided into seven sections; namely, benefit-risk analysis which focuses on the effects of a false positive or a false negative, device description and specifying the intended use which takes into account each component in order to effectively monitor treatment. This would include the nature of the analyte, specimen types in which testing may be carried out, the specific population for which the test is intended and the intended use setting. Then comes establishing performance characteristics – analytical validation studies which understand the individual biological differences that are bound to occur between patients, establishing performance characteristics – animal studies as surrogates for clinical validation which recognizes the possible difficulties that can arise due to the testing of humans, establishing performance characteristics – clinical validation studies with human samples motivating manufacturers to carry out further tests with a complete plan provided with a suitable statistical analysis to be completely sure, labeling to help developers identify extrinsic factors or other confounding variables that may interfere with the results and provide a comprehensive review of both quantitative as well as qualitative data. And lastly, CLIA categorization for respecting the need for individual testing. The CLIA regulation incorporates three levels of test complexity i.e., waived tests, moderate complexity tests and high complexity tests.
A suitable timeframe for the device mentioning both the beginning and end of time exposure should be included and a detailed desired purpose for using the device along with limitations that may interfere with the results. For a biodosimeter study, the need for a statistical analysis plan (SAP) is highly essential. The SAP should comprise of a sample size, design of the study and a valid statistical method. The SAP should also cover the procedure in case of missing values and data in order to reach a conclusion. If results are qualitative, interpretations explaining both positive and negative aspects should be provided.
FDA also urges sponsors to review the pre-submission program to acquire further data in order to expand the product and for those who plan to market it, they must comply with the rules provided by the Federal Food, Drug and Cosmetic Act (FD&C Act).