October 31, 2003
The FDA previously commented on particulate matter observed in blood bags. This notice updates that February 7, 2003, statement.
Early this year, the American Red Cross (ARC) reported finding multiple units of blood and blood components that contained white particulate matter in a small percentage of blood bags manufactured by Baxter Healthcare Corporation (Baxter) and identified in the ARC Southern region. Subsequent reports revealed that this phenomenon also affected blood and blood components collected in bags made by other companies, and collected by ARC and non-ARC establishments in other areas of the country. Based on conditions under which the initial observations were made, FDA commented that it would be an appropriate interim measure to inspect blood bags visually prior to leukofiltration, at the time of packing for distribution, and after placing the bags, label down, on a flat counter, undisturbed for 10 minutes. Studies performed to date have failed to show any increase in adverse events, any correlation of adverse events with presence of particulates, or any anomalies in the manufacture of blood bags that could have caused an increase in formation of particulates. Therefore, FDA currently believes there is no additional value provided by the enhanced visual inspection.
Numerous investigations by Baxter and other blood bag manufacturers, FDA, NIH, CDC and ARC focused on the nature of the particles and the possible cause of their formation. Physical characterization of the particles themselves revealed them to be composed of normal blood elements (aggregates of platelets, with variable amounts of fibrin and trapped red and white cells) and not of extraneous material or organisms. The formation of similar aggregates has been well reported in previously published literature. In addition, unintended changes in the composition of the blood bags themselves and their contents, which might have contributed to an increase in particle formation, could not be demonstrated. (Certain changes related to storage of the blood bags remain under study.) The frequency of formation of visually detectable particulates was correlated with absence of leukocyte reduction and with the use of higher g-forces in centrifugation to make components. Leukocyte filtration was demonstrated to remove most observable particulates.
Epidemiological investigations by the Georgia Department of Public Health in conjunction with CDC and blood centers that may have received affected products addressed the question whether any change had occurred in the frequency of adverse events from transfusion over the 12 months prior to and including the time period associated with recognition of unusual particulates in blood components. In addition, two blood centers prospectively collected data on the frequency of adverse events associated with leukofiltered and non-leukofiltered units, and any correlation with presence of particulates. No increase in adverse events was seen either as a general national trend or in specific hospitals and blood centers that made efforts to identify adverse reactions that might have been associated with particulates in released units. Although these studies found no evidence for an increase in the frequency of adverse events from transfusion associated with the recent observations of particulates, and units with particulates were not associated with more frequent adverse events than those without, the available data cannot conclusively rule out a potential association between particulate formation in blood units and some adverse events included in historical background rates. FDA therefore remains interested in the investigation of formation of particulates in blood units and their potential relevance to transfusion safety.
FDA's regulations call for visual inspection of blood and blood components during storage and immediately prior to distribution and issuance (21 CFR 606.160(b)(3)(ii), 640.5(e)). Pending investigations into the original reports of unusual findings of particulate matter in blood units, FDA considered the additional procedures mentioned above to be appropriate as an interim precautionary measure. Along with this inspection, blood establishments were encouraged to report observations of these particles in blood or blood components, quarantine the affected products and report findings expeditiously to FDA at the following e-mail address: BP_Deviations@cber.fda.gov or by phone at 800-835-4709. Based on the studies summarized above, FDA currently believes that there is no additional value provided by the enhanced visual inspection, and therefore it would be appropriate for blood establishments to discontinue that procedure. However, because the data cannot conclusively rule out a potential association between particulate formation in blood units and some adverse events, it may be appropriate for blood establishments to consider the use of leukocyte reduction as a measure to reduce the frequency of particulates in released units.