New Draft Guidance and the Potential Impact on Platelet Inventories

August 17, 2020 by Carter BloodCare Specialty Services

by Geeta Paranjape, MD

Background
The reported rates of septic transfusion reactions from platelets vary from 1/100,000 by passive surveillance to 1/10,000 by active surveillance when testing with primary culture alone. Surveillance data on platelets stored up to five days have shown that the majority of platelet transfusion-related septic reactions and associated fatalities have occurred with transfusion of day four and day five stored platelets.

The FDA has established regulations to address the control of bacterial contamination of platelets. Under 21 CFR 606.145(a), blood establishments and transfusion services must assure that the risk of bacterial contamination of platelets is adequately controlled using FDA approved or cleared devices, or other adequate and appropriate methods found acceptable for this purpose by the FDA.

Currently, this risk can be controlled by bacterial testing or pathogen reduction methods.

Bacterial testing includes the use of culture-based or rapid detection tests. While primary testing is typically performed by culture and within 24 hours of collection, secondary testing is performed at later times of storage and prior to transfusion. Pathogen reduction is performed shortly after platelet collection.

Under 21 CFR 610.53(b), the dating period for platelets with a storage temperature between 20 and 24 degrees Celsius is five days from the date of collection. The current maximum dating period for platelets can be extended to seven days provided the storage container is FDA approved for seven days and rapid testing is performed. Current expiration date for platelets treated with pathogen reduction technology is five days. In the draft guidance document (published December of 2018 and open for comments), the FDA has proposed the following methods.
Table 1. Summary Table of FDA’s Recommendations

The recommendations posed by the FDA will result in a disruption to the current manner that platelet inventories are managed, add cost to provide the final component, and most likely require hospital transfusion services to implement rapid testing to meet urgent transfusion needs.

Pathogen reduction option

Currently, there is only one approved pathogen reduction technology available for use in the U.S. The technology is not comprehensive in its use and cannot be used for testing of pre-storage whole-blood derived pools or triple apheresis collections. Additionally, the processing method has content and volume limitations for effective treatment that cause a decrease in the apheresis split rate. As a blood collection facility, without major changes to how we collect, the option to use and distribute pathogen reduced platelets could significantly impact our ability to meet the current need for platelet components.

5-day or 7 day storage primary culture + secondary culture/rapid testing

Currently, Carter BloodCare elects to rotate and restock apheresis platelets maintained on site at multiple healthcare facilities in order to meet the daily, unpredictable demand for platelets. This model allows Carter BloodCare to maximize the use of this limited resource and minimize outdates. While there is currently no additional charge for this service, this model is most likely unsustainable with the need to re-test (secondary culture or rapid point of issue testing) and re-label. Secondary culture and rapid testing is not feasible as the component is at the hospital transfusion service and would need to be returned to the blood center and then delivered back to the hospital for use after sampling. The logistics involved present a challenge, but of more importance is the available transfuseable inventory that will be reduced due to the time period to re-test and re-label. Hospital transfusion services should be prepared to implement rapid testing to ensure a readily transfuseable platelet is always maintained on-site.

7–day storage large volume delayed sampling

Large volume delayed sampling at 48 hours post collection and incubating for an additional 12 hours means that platelets will not be available for 60 hours post collection. Additionally, the large volume requirements could result in a reduced platelet yield per component. While this option is promising and places fewer burdens on the hospital transfusion service, there is currently no methodology licensed for this option. We encourage you to urge the FDA not to finalize the guidance until this option is available.

To review the guidance in its entirety, please visit the FDA website at:
https://www.fda.gov/downloads/BiologicsBloodVaccines/GuidanceComplianceRegulatoryInformation/Guidances/Blood/UCM627407.pdf

Any of the final recommendations will result in a strain on the current platelet supply, which is already challenged by the unpredictability in usage. The hospital’s burden to implement rapid testing may increase; some methods will result in a decreased number of platelet products that can be made available from a single donation which creates additional pressures on the blood center to recruit more donors. Overall, the final guidance will inevitably require a more collaborative and innovative platelet management model than we have seen in the past.

Table 1. Bacterial Risk Control Strategies for Blood Collection Establishments and Transfusion Services to Enhance the Safety and Availability of Platelets for Transfusion, FDA draft guidance, December 2018.