THE AMERICAN ASSOCIATION OF BLOOD BANKS
Presented by Kay R. Gregory, MS, MT(ASCP)SBB
Director, Regulatory Affairs, AABB
The American Association of Blood Banks (AABB) is the professional society for over 8,000 individuals involved in blood banking and transfusion medicine and represents approximately 2,000 institutional members, including blood collection centers, hospital-based blood banks, and transfusion services as they collect, process, distribute, and transfuse blood and blood components and hematopoietic stem cells. Our members are responsible for virtually all of the blood collected and more than 80 percent of the blood transfused in this country. For over 50 years, the AABB's highest priority has been to maintain and enhance the safety and availability of the nation's blood supply.
The AABB believes that bacterial contamination of platelets is the most significant current infectious threat from blood transfusion and appreciates the opportunity to comment on this issue. For decades, bacterial contamination has been recognized as a significant risk associated with room-temperature storage of platelets. The AABB believes the time has now come to take action on this issue.
As other infectious risks of transfusion have been reduced, the magnitude and relative importance of bacterial contamination of platelets has become more pronounced. Various innovative strategies have been and are being developed to address this risk. Although no single method or strategy provides a perfect solution, the AABB believes that multiple approaches may be appropriate for consideration. Methods to prevent and detect bacterial contamination in both apheresis and pooled platelets made from whole blood have been implemented in other countries. These methods have undergone clinical evaluation in this country, demonstrating the ability to detect some bacterially contaminated units. The AABB notes that the FDA has recently approved two culture-based bacterial detection systems for quality control testing of leukocytes-reduced platelets. At this critical juncture, the AABB sees a valuable opportunity for cooperation between the transfusion medicine community and FDA.
The AABB reviews its voluntary Standards for Blood Banks and Transfusion Services on a planned basis. The next edition of these Standards, the 22nd edition, has just been published for public comment and proposes two significant changes with regard to decreasing the risk of bacterial infection for recipients of platelet transfusions.
The first focuses on prevention of bacterial contamination of the donated unit, and involves changes to the skin preparation method. Based on the data reviewed, AABB has recommended that alcohol/tincture of iodine be the method of choice, with chlorhexidine being acceptable for individuals who are allergic to iodine. On the basis of data reviewed, the Standards Committee has concluded that green soap is not acceptable for skin preparation.
The second change the AABB has proposed is a draft standard requiring that facilities have “method(s) to detect bacterial contamination in all platelet components.” In light of the fact that no single system or method is effective in eliminating the risk of bacterial contamination in all components, the AABB has declined to be specific as to the method(s) of bacterial detection required in this proposed standard. There are a number of logistical and scientific issues to be resolved prior to implementation of any detection system, but the AABB believes it is critical to begin to address these issues now. The AABB recognizes that some facilities may opt to use a method that gives immediate results, while others may be able to adopt culture techniques.
It is also relevant to note that this proposed standard would require screening of all platelet components. If the goal is to reduce infections in recipients, it is essential that all platelet components be evaluated. A statistical sampling approach runs the risk of not effectively decreasing the rate of bacterial infection.
It is much more feasible and practical from both a logistical and a product loss standpoint to perform bacterial detection, especially using culture methods, on apheresis platelets. However, the entire need for platelet transfusion is not currently, nor will it be in the foreseeable future, met by single donor apheresis platelets. Whole blood derived platelets are necessary to ensure an adequate supply of platelets. The potential application of culture methods to detect bacterial contamination in apheresis platelets cannot be allowed to render platelets from whole blood an undesirable component. To this end, the AABB recognizes that detection techniques such as Gram’s or Wright’s stain, or dipstick monitoring may initially need to be used for whole blood derived platelets.
The AABB believes that the FDA can facilitate bacterial detection of whole blood derived platelets by reexamining its current thinking under which platelets pooled in either the blood collection facility or the transfusing facility, regardless of the use of sterile methods, cannot be used beyond four hours after pooling. The FDA’s current thinking makes the culture of pooled platelets impossible. In the interim, alternative (albeit less ideal) methods, including microscopy with acridine orange, Wright’s or Gram’s stains, or dipstick monitoring of glucose and/or pH with appropriate thresholds are available for use at the time pooled platelets are released. The FDA appears to have indicated that it would require in vivo studies of platelet effectiveness before considering extending the storage of platelets pooled using sterile methods to 5 days, as is currently allowed for non-pooled product. However, such in vivo studies are difficult to perform, expensive, require the enrollment of large numbers of patients from multiple institutions, and are difficult to analyze due to multiple, unavoidable confounding factors. In light of existing in vivo data from Europe concerning the 5-day storage of pooled platelets derived by the buffy coat method and in vitro data showing the similarity between platelet rich plasma derived platelets and buffy coat platelets, the AABB urges the FDA to examine ways in which it could expedite approval of the extended storage of a pooled platelet product.
The AABB also urges the FDA to act quickly to consider what data will be required to extend platelet storage to 7 days, provided that an acceptable bacterial detection system is used.
In light of the challenges and tremendous opportunity for improving the safety of the blood supply through the implementation of the bacterial contamination methods described above, the AABB requests the following assistance from FDA:
1. Regulatory support towards accomplishing AABB’s current goal of requiring bacterial detection and interdiction of contaminated products;
2. Regulatory support in developing consensus on arm preparation solutions and techniques, with a specific emphasis on prohibiting the use of green soap;
3. Discussion of the data required to increase the storage time for pooled platelets (with a particular focus on whether in vitro data on platelet bacterial growth rates is acceptable);
4. Discussion of the data needed to extend the outdate of platelets to 7 days.
As has been the case relating to the development of new tests for emerging infectious diseases, the blood banking and transfusion medicine community and the FDA must understand the need to implement less than perfect solutions, while we work to improve the available methodology and technology, recognizing that such incremental steps will improve the safety of the blood supply.