March 5, 2003
The Food and Drug Administration's (FDA) Center for Biologics Evaluation and Research (CBER) has recently received inquiries regarding the freezing and irradiation of red blood cells collected on Gambro BCT TRIMA and Baxter Amicus and ALYX apheresis instruments in ACD-A/AS-3 or ACD-A/AS-1 anticoagulant/preservative solutions. It has come to FDA's attention that red blood cells collected in various anticoagulant/preservative solutions used for both manual and automated collections are being frozen, irradiated or both without prior approval of these solutions for use in conjunction with those procedures. This information update is intended to provide FDA's current thinking on the use of unapproved solutions for freezing and/or irradiation of red blood cells.
The freezing and/or irradiation of red blood cells under conditions not yet approved by FDA may raise safety and efficacy concerns regarding these products. Both freezing and irradiation can damage red blood cells causing them to be more prone to hemolysis, or more rapidly cleared from the circulation after transfusion. Because there are unique concerns with irradiation and freezing procedures, we are addressing these procedures separately.
Irradiation of certain lifesaving blood products is a procedure necessary to prevent potentially fatal complications of graft versus host disease from use of those products. Although no anticoagulant/preservative solutions have been specifically approved for use in combination with irradiation, the safety data for irradiated products encompassed the use of a variety of solutions. Based on these considerations, it has been our policy to approve irradiation as a process that can be performed on products collected in all anticoagulant/preservative solutions. Additionally, we recognize that the use of the products has appeared to be safe in clinical practice. Therefore, FDA will continue to allow products collected in the anticoagulant/preservative solutions that are currently approved, to be irradiated. However, we intend to request data to support specific licensure of irradiated products collected in new anticoagulant/preservative solutions.
Currently, FDA has approved several red blood cell - anticoagulant/preservative solution combinations to be used to prepare red blood cells for freezing with a 10 year storage period. These include:
- CPD Red Blood Cells
- CPDA-1 Red Blood Cells
- CPDA-1 Rejuvenated Red Blood Cells
- CPD/AS-1 Rejuvenated Red Blood Cells
Although we consider it appropriate for blood centers to freeze red blood cells only in the approved anticoagulant/preservative solutions listed above, we recognize that it is currently in the best interest of public health to allow the continued use of frozen red blood cells prepared in other anticoagulant/preservative solutions. The Agency's current thinking is based on recognition of the present strain on the nation's blood supply and the long period during which red blood cells have been frozen using other anticoagulant/preservative solutions without reports of adverse events linked specifically to the solutions used for freezing red blood cells. However, in view of the potential safety and efficacy concerns for red blood cells collected in unapproved anticoagulant/preservative solutions, we are requesting that blood centers and blood collection system manufacturers submit data to support licensure of the anticoagulant/preservative solutions when used to manufacture frozen red blood cells.
Although FDA shares the concerns voiced by industry on the potential impact to the blood supply if current procedures were to be abruptly discontinued, we would like to resolve the safety and efficacy concerns as soon as possible. We hope that the clinical trials performed by the device or blood collection system manufacturers will address our concerns about the safety and efficacy of irradiated and frozen red blood cells collected in the various anticoagulant/preservative solution combinations. The automated collection device manufacturers have willingly agreed to sponsor studies on red blood cells collected and stored in anticoagulant/preservative solutions approved for their devices. When appropriate data becomes available, we will consider publishing guidance on use of approved anticoagulant/preservative solutions in the preparation of frozen and/or irradiated red blood cells.