Vaccines, Blood & Biologics
Frequently Asked Questions on FDA's Continuing Investigation of Particulate Matter in Blood
What are the particulates?
Evaluations of the particulates suggest that they primarily consist of platelets and some white blood cells, red blood cells and, in some cases, fibrin.
What causes them?
Although there is not currently a definitive answer to this question, one theory under investigation by FDA and the blood centers is that the observed particles may result from certain conditions of blood handling. Whole blood is composed of red blood cells, plasma, white cells, and platelets. It is a long-term practice in the blood industry, when blood platelets are not being prepared from whole blood, to allow the platelets to remain in red blood cell units during and after processing to remove plasma. Because platelets are known to sometimes form visible particulates, leaving them in the red blood cell fraction of the blood may lead to the observed particulates.
Why are they being observed now?
With the availability in recent years of automated methods for platelet collection that yield more platelets from fewer donors, whole blood donations are less commonly used as a source of platelets. In these whole blood donations, it is efficient to leave the platelets in the RBC fraction of the blood. It is known that platelets sometimes form visible particulates. Thus, this phenomenon has always been present but is apparently being observed more frequently now.
Should Blood Centers be using enhanced visual inspection for particulates?
Blood establishments are required under the regulations to do visual inspections. As a result of the finding of particulate matter, FDA became aware that some blood organizations were enhancing their visual inspection procedures. In light of the uncertainty surrounding the particulates, FDA stated that it considered such procedures to be an appropriate interim step. Based on information from a number of sources in the blood and health industries, FDA is reminding blood collection establishments to inspect all blood and blood components using an enhanced procedure.
Are these particulates associated with illness or adverse events in recipients?
Early reports of adverse events in patients who had received blood that might have conceivably contained such particulates raised the question of whether they could be harmful. However, follow up investigations by the blood centers have so far failed to provide any evidence of increased adverse reactions among patients who may have received potentially implicated blood transfusions. In addition, one epidemiological study has not demonstrated an increase in adverse events over the past year. The FDA, CDC and state health departments are continuing to investigate the possibility of adverse reactions, but at this point we are not aware of evidence indicating an increase in adverse events due to particulate matter.
If a blood center leukoreduces all of its units, should they also use enhanced visual inspection procedures following leukoreduction?
As stated above, FDA regulations require visual inspection procedures during storage and immediately before distribution (21 CFR 606.160(b)(3)(ii) and 640.5(e)). Particulates have been observed in leukoreduced red blood cell products at a greatly diminished frequency. However, the medical director of each blood center should consider whether to utilize enhanced visual inspection techniques, above and beyond those that should already have been in place to comply with FDA regulations.
If particulates are observed in blood units during an enhanced visual inspection, can the units be used after filtration using leukocyte reduction filters?
It is FDA's thinking that units with observed particulates may be used after the blood products are filtered using procedures that are adequate to remove white cells.
If all units are observed with the suggested enhanced visual inspection, and affected units removed, is leukoreduction necessary for units for which no suspect particulates are observed?
No. Although leukoreduction provides known benefits to selected blood recipients and many believe that it provides additional, more general, benefits, FDA does not currently require leukoreduction of all units. If units are not normally leukoreduced and particulates are not observed, we do not believe that the units pose an increased risk.
If I notice particulates in an autologous unit of blood after storage, may I use it?
As mentioned above, it is FDA's thinking that autologous units with observed particulates may be used after the blood products are filtered using procedures that are adequate to remove white cells. As always, the medical director should use discretion and the concerns of the patient should be addressed.
Are blood (170 micron) transfusion filters sufficient to remove particulates?
These filters are important and have been used safely for many years. Their ability to remove the particulate matter that has been recently observed is unverified. FDA is aware of proposals to study this question in vitro but results are not yet available. Pending further studies, it is FDA's current thinking that units with observable particulates should be quarantined rather than used, unless they are filtered with filters designed to remove leukocytes. However, medical directors may exercise independent judgment in this area.
If I add an enhanced visual inspection to my blood processing procedures prior to leukoreduction, do I need to repeat it before distribution?
FDA's regulations require visual inspection procedures during storage and prior to distribution, and these regulations must be followed. However, because an initial enhanced visual inspection may help to identify any units with particulate matter, and because leukoreduction greatly reduces the number of units containing particulates, a second inspection after leukoreduction probably would not add significant benefit to the safety of the blood. FDA's current thinking is that the enhanced inspection of whole blood and red cells is best performed by the collection centers prior to leukoreduction and need not be repeated after leukocyte reduction or by transfusion services.
Should blood centers continue to visually inspect?
Yes. As described in regulation, visual inspection is required during storage and prior to distribution. The enhanced visual inspection should still be considered prior to leukoreduction. The benefit of an additional enhanced observation post leukoreduction probably does not add significant benefit.
Should transfusion services continue to visually inspect?
If transfusion services receive blood units from other blood collectors who have either leukoreduced the units and/or added an enhanced visual inspection, enhanced observation by the transfusion service prior to distribution probably does not add significant benefit. Implementation of the enhanced visual inspection is expected to have its greatest value during the manufacturing process of the blood component. FDA currently believes that routine visual inspections at the transfusion service prior to distribution are adequate.
May I release for distribution in-date components that were collected prior to instituting enhanced inspection but were leukoreduced and have not been transfused?
Yes, so long as such products underwent the visual inspection and other requirements described in FDA regulations, the fact that they did not undergo an enhanced visual inspection does not mean that they cannot be released.