Ahead of the Radiological Devices Advisory Panel meeting on Tuesday, FDA reviewers noted that the agency's proposal to classify salvaged blood irradiators as high-risk Class III devices is based on a dearth of information supporting safety, and no data supporting their benefits.
The panel is being asked to make recommendations on whether these devices -- used to prevent metastasis during surgery -- are safe enough for a Class II designation, or whether they should be designated to the highest-risk category.
While not scheduled to be part of the panel's discussions, the U.S. Government Accountability Office has warned that in the hands of terrorists, some of these devices given that they can rely on high-risk radioactive materials.
According to FDA , a literature review that spanned 21 years turned up only 10 studies on these devices. However, none of them specifically mentioned either of the two irradiators cleared in the U.S. Furthermore, none of these studies were randomized controlled trials, were conducted in the U.S., or discussed risks or performance issues, leading FDA staff to conclude that "the data to support effectiveness of irradiation of intraoperatively salvaged blood to prevent metastasis is sparse."
They also pointed out that "blood irradiation of intraoperatively salvaged blood in order to prevent metastasis does not currently appear to be a widely used technique."
Both of the cleared devices are indicated for cancer patients undergoing tumor resection who are not candidates for a blood transfusion. The devices collect blood and run it through an x-ray exposure chamber with the intent of destroying tumor cells that are in circulation or have been liberated by the surgical procedure.
Blood irradiators for the prevention of metastasis are a pre-amendments, unclassified device type, FDA staff noted. "This means that this device type was marketed prior to the enactment date of the Medical Device Amendments of 1976 ... but was not classified by the original classification panels. Currently, these devices are being regulated through the 510(k) pathway, and are cleared for marketing if their intended use and technological characteristics are 'substantially equivalent' to a legally marketed predicate device."
However, since they're unclassified, they're in regulatory limbo. Adding to the confusion is the shared administrative oversight between two regulatory branches.
"Blood irradiators as medical devices are among a few medical devices that are jointly regulated by the Center for Biologics Evaluation and Research (CBER) and the Center for Devices and Radiological Health (CDRH)," FDA reviewers wrote.
"Irradiators intended for use in the inactivation of immunologically active cells in whole blood, red blood cells and platelets are regulated by CDRH with consultation by CBER on the safety and effectiveness of the irradiated product," they explained. "Irradiators intended for use in the in-process inactivation of HIV viruses or other pathogens in all blood products, licensed biological products, or analogous products will be regulated by CBER with consultation by CDRH."
Although the literature review didn't identify any documented health risks, FDA staff contended that there is insufficient information to provide "reasonable assurance" of the safety of these devices for this indication.
They also identified some potential risks:
- Active malignant cells could be re-perfused into the patient if the radiation dosage is incorrect, which could result from operator error or maintenance issues
- Irradiated blood might stimulate an immune reaction that could worsen the patient's prognosis
- Radiation could damage red blood cells
- Unintentional radiation leaks could expose the operator, patient, and other people in the surgical suite to unnecessary radiation
- The device itself could malfunction, causing an electric shock, or it could fall and cause a crush injury
The literature review also failed to substantiate much efficacy, FDA reviewers noted.
"Based on the information we could collect, there is inadequate evidence to draw any definitive conclusions about the effectiveness of the use of blood irradiators to irradiate intraoperatively salvaged blood to assist in the prevention of metastasis in cancer patients undergoing surgery," they wrote.
"The one observational study that included re-transfusion of irradiated intraoperatively salvaged blood, contained a control arm, and followed patients for tumor recurrence ... but only examined occurrence of metastasis in patients with one type of cancer, had a small sample size of 10 patients across three arms, and all patients received transfusion of allogeneic blood components," they added. "While infusion of salvaged blood did not increase tumor recurrence rates, there was also no reduction seen in patients receiving salvaged blood that had been irradiated."
If the committee doesn't feel a Class III indication is merited, the FDA will want members to discuss their reasoning.