Comment from Anonymous

Comments and Questions On Timeline for PMA Submission (Section III) * Comment: The proposed 30-month compliance window for manufacturers to file a PMA after the final order is issued is excessively long and should be compressed to 12 or 18 months to minimize patient exposure to unvalidated devices. (Speculative) * Supporting Evidence: While novel Class III applications can take up to a year to review, allowing high-risk metastasis prevention devices to remain on the market without a completed PMA for over two years presents an unnecessary and ongoing public health risk. Source: Daeryun Law, 2026, [https://www.daeryunlaw.com/us/practices/detail/premarket-approval](https://www.daeryunlaw.com/us/practices/detail/premarket-approval) On Radiation Dose Standardization (Section V.C) * Comment: The FDA must mandate clear clinical and technical protocols within the PMA framework to resolve the current lack of professional consensus regarding the optimal radiation dose for tumor inactivation. * Supporting Evidence: Historically reported doses range from 25 to 50 Gy, creating an unacceptable variance that can result in either incomplete tumor cell eradication or catastrophic erythrocyte damage. Source: PMC, 2014, [https://pmc.ncbi.nlm.nih.gov/articles/PMC4165080/](https://pmc.ncbi.nlm.nih.gov/articles/PMC4165080/) On Clinical Trial Diversity and Health Equity (Section VI) * Comment: PMA submission requirements should explicitly mandate demographic diversity in clinical trials to ensure that efficacy data is generalizable across racially and socioeconomically diverse patient groups. * Supporting Evidence: Significant health equity disparities persist in oncology care, and ensuring clinical trials reflect diverse demographics avoids compounding systemic biases in medical device efficacy evaluation. Source: PMC, 2025, [https://pmc.ncbi.nlm.nih.gov/articles/PMC12251436/](https://pmc.ncbi.nlm.nih.gov/articles/PMC12251436/) On Product Code Bifurcation and Adverse Event Tracking (Section IV) * Comment: The FDA should immediately create and enforce a separate, distinct product code for metastasis-prevention blood irradiators separate from those used for transfusion-associated graft-versus-host disease (TA-GVHD) to optimize post-market surveillance. * Supporting Evidence: Segmented product codes are necessary to accurately isolate and monitor unique adverse outcomes, such as local or systemic cancer recurrence, within the MAUDE database. Source: FDA Regulatory Impact Analysis, 2026, [https://www.fda.gov/about-fda/economic-impact-analyses-fda-regulations/medical-devices-radiology-devices-classification-blood-irradiators-regulatory-impact-analysis](https://www.fda.gov/about-fda/economic-impact-analyses-fda-regulations/medical-devices-radiology-devices-classification-blood-irradiators-regulatory-impact-analysis) On Environmental and Safety Risks of Radioactive Sources (Section VII) * Comment: The FDA should utilize the PMA process to strongly incentivize or mandate a technological transition from radioactive isotopes like Cesium-137 to modern X-ray tube technologies. * Supporting Evidence: Phasing out cesium-based sources protects urban community healthcare infrastructure from catastrophic radiological liabilities, security costs, and the societal threat of dirty bombs. Source: Nuclear Threat Initiative, 2018, [https://www.nti.org/analysis/articles/cesium-137-blood-irradiator-replacement/](https://www.nti.org/analysis/articles/cesium-137-blood-irradiator-replacement/) On In Vivo Clinical Endpoints (Section V.A) * Comment: The FDA must specify that in vitro evidence of tumor cell death is insufficient for PMA clearance and require robust, long-term in vivo clinical efficacy endpoints. * Supporting Evidence: Prior systematic reviews indicate that existing professional guidelines rely heavily on weak in vitro data, leaving significant uncertainty regarding actual in vivo tumor recurrence prevention and overall patient survival. Source: FDA Radiological Devices Advisory Panel, 2023, [https://www.fda.gov/media/173451/download](https://www.fda.gov/media/173451/download) On Cellular Integrity and Safety Monitoring (Section V.C) * Comment: The proposed rule must require manufacturers to include comprehensive post-irradiation analysis of erythrocyte structural integrity and potassium level fluctuations in their PMA applications. * Supporting Evidence: Inadequate or imprecise dosing can cause rapid cell degradation and dangerous hyperkalemia, posing acute physiological risks to patients during autologous reinfusion. Source: AABB, 2026, [https://www.aabb.org/news-resources/news/article/2026/03/18/regulatory-update--fda-proposes-new-classification-rule-for-blood-irradiators-used-to-prevent-ta-gvhd](https://www.aabb.org/news-resources/news/article/2026/03/18/regulatory-update--fda-proposes-new-classification-rule-for-blood-irradiators-used-to-prevent-ta-gvhd)