21 September 2012
Considerations for Options to Further Reduce the Risk of Bacterial Contamination in Platelets
M. Allene Carr-Greer, Director, Regulatory Affairs
AABB is an international, not-for-profit association representing individuals and institutions involved in the field of transfusion medicine and cellular therapies. The association is committed to improving health by developing and delivering standards, accreditation and educational programs that focus on optimizing patient and donor care and safety. AABB membership consists of nearly 2,000 institutions and 8,000 individuals, including physicians, nurses, scientists, researchers, administrators, medical technologists and other health care providers. AABB members are located in more than 80 countries.
AABB thanks you for the opportunity to speak today. We also wish to thank the Food and Drug Administration for addressing the issue of bacterial contamination of platelet components in a public venue. AABB has addressed this issue on several fronts during the past decade and we appreciate the opportunity to provide a record for this meeting of the actions AABB has required member facilities to take to limit and detect bacterial contamination in platelet components and of education provided to the membership to support implementation of the various requirements and recommendations.
AABB strategies have been developed using the expertise of members of its Bacterial Contamination Task Force, Transfusion Transmitted Diseases Committee, and Blood Bank and Transfusion Service Standards Program Unit. The method for AABB policy and requirements to be communicated to accredited members is through publication of Association Bulletins and development of Standards. The current requirements of an accredited AABB member, applicable to today's discussion, as published in Standards for Blood Banks and Transfusion Services (28th edition) are listed here. The standards were also applicable in the 27th edition.
| || ||Aseptic methods shall be employed to minimize the risk of microbial contamination of blood and blood components. Equipment and solutions that come into direct contact with blood or blood components shall be sterile and pyrogen-free. Single-use equipment shall be used whenever possible.|
| || ||220.127.116.11||The blood bank or transfusion service shall have methods to limit and to detect or inactivate bacteria in all platelet components. Standard 5.6.2 applies.|
| || || ||18.104.22.168.1||Detection methods shall either be approved by the FDA or be validated to provide sensitivity equivalent to FDA-approved methods.|
| || ||22.214.171.124||When a true-culture positive result is obtained and an appropriate specimen is available, additional testing to identify the organism shall be performed. Additional testing and followup shall be defined. Standards 5.2.4 and 7.1 to 7.1.4 apply.|
| || ||Blood shall be collected into a sterile closed system.|
| ||5.6.2||Protection Against Contamination|
| || ||The venipuncture site shall be prepared so as to minimize risk of bacterial contamination. Green soap (USP) shall not be used.|
| || ||126.96.36.199||Blood collection containers with draw line (inlet) diversion pouches shall be used for any collection of platelets, including whole blood from which platelets are made.|
Early strategy focused on moving the membership away from the use of green soap to prepare venipuncture sites and toward the use of pouches that divert the first milliliters of blood withdrawn from the donor, potentially containing a contaminated skin plug, into tubes used for testing rather than flowing into a collection bag.
BB/TS Standard 188.8.131.52 was published in 2003 in the 22nd ed. with an effective date of March 1, of 2004. Practically, the result of implementation of Standard 184.108.40.206. was detection of bacterial contamination in apheresis platelets by culture-based methods. Eventually this included pre-storage pooled whole blood-derived platelets. Remaining whole blood-derived platelets were evaluated using a variety of methods including the use of pH and glucose readings, as well as observation of swirling.
Association Bulletin #03-12 issued October 1, 2003 – Further Guidance on Methods to Detect Bacterial Contamination of Platelet Components – was a comprehensive document that provided the membership with 1) background information on the risk to recipient safety posed by bacterial contamination of platelets and the underpinnings of the approaches that had been considered to limit and detect contamination, 2) practical guidance on the implementation of some of the techniques, and 3) sample plans and algorithms.
Association Bulletin #04-07 issued October 14, 2004 – Actions Following an Initial Positive Test for Possible Bacterial Contamination of a Platelet Unit – is still an active bulletin.
Association Bulletin #09-04 issued July 20, 2009 – Developments in Bacterial Testing and BBTS Standard 220.127.116.11. – reviewed what was then the current status of technology available to meet the intent of Standard 18.104.22.168 and provided an update on new technologies in development that would offer an alternate method for meeting the standard. It also informed members that once studies demonstrated the efficacy of an alternate method in detecting bacteria in whole blood-derived platelets (similar to the studies required for FDA approval), AABB would likely adopt a more prescriptive interim standard.
BB/TS Interim Standard 22.214.171.124.1 was announced in Association Bulletin #10-02 issued May 3, 2010 and became effective January 31, 2011. The Standard was subsequently published in the 27th edition.
Association Bulletin #10-05 issued August 19, 2010 – Suggested Options For Transfusion Services and Blood Collectors to Facilitate Implementation of BB/TS Interim Standard 126.96.36.199.1 – was published to assist transfusion services with making a complete transition away from surrogate testing (pH and glucose) to culture-based or rapid immunoassay (point-of-issue) bacterial screening. Another option provided was use of approaches or methods that were not FDA-cleared but that had been validated to be of equivalent clinical sensitivity to an approved assay.
In July of this year AABB provided the opportunity for public discussion of issues surrounding the remaining residual risk of bacterial contamination of platelet components. While a variety of experiences and data were presented and discussed, the focus of the workshop was apheresis platelets and the impact secondary screening for bacterial contamination has had and might have if more broadly applied. FDA did not co-sponsor the workshop but was represented on the planning committee. As follow-up to the public conference AABB is reviewing its current policy and will issue further recommendations in an Association Bulletin.
Because AABB recognizes the remaining residual risk of bacterial contamination in apheresis platelets, the association welcomes guidance from FDA on ways to reduce this risk. Multiple approaches, in addition to those proposed by FDA today, require careful consideration. Any further actions, however, must be validated as to their efficacy and impact on patients who depend on platelets for treatment. Specifically, no change should be advocated in the absence of a careful evaluation of the impact on platelet availability.