The Circular of Information (the Circular) is made available through the important work of the AABB's Circular of Information Task Force. This webpage provides the background information for compliance with FDA requirements under 21 CFR 606.122 for use of the Circular, including information on purchase options, implementation, and updated language. AABB encourages you to review the information for important changes.
Please contact Regulatory Affairs with your questions at
The User Guide for the December 2021 Circular provides blood collection establishments, transfusion services and clinical staff with information to supplement their understanding of the regulatory responsibilities for implementation and use of the Circular. The User Guide also provides information about appropriate use of the electronic version of the Circular (eCircular provided in USB format to blood manufacturers). The User Guide includes a Change Table highlighting significant changes and new information included in the December 2021 Circular. New in this version:
AABB has made the Circular publicly available for review (as a pdf document) to ensure access to the content. This posted watermarked version may not be copied, printed or used as the extension of labeling.
According to 21 CFR 606.122, a Circular of Information must be available for distribution if a blood product is intended for transfusion. As new products for transfusion become available, new testing requirements are implemented or new information becomes available, the December 2021 Circular must be updated to accurately reflect the changes. Until the new language is incorporated into the next version of the Circular and consistent with historic practices, AABB recommends:
NOTE: The version date of December 2021 for the Circular must not be changed.
Cryoprecipitated AHF is manufactured from plasma, as defined in 21 CFR 640.50 (a) and (b). Historically, blood establishments have prepared Cryoprecipitated AHF from Fresh Frozen Plasma (FFP).
Establishments that wish to prepare Cryoprecipitated AHF from other types of plasma such as PF24 should contact FDA to determine what to submit for review. In some instances, blood establishments may need to request an alternative or exception to applicable regulations if the plasma collection set is labeled for the collection of FFP only.
FDA required update to the Circular
Until new language is incorporated into the next version of the Circular, facilities that manufacture Cryoprecipitated AHF from PF24 may update their December 2021 Circular with the following language:
“Cryoprecipitated Antihemophilic Factor (AHF) is prepared by thawing whole-blood-derived or apheresis PF24 between 1 and 6 C and recovering the precipitate.”
“Plasma Cryoprecipitate Reduced is prepared from whole-blood-derived or apheresis PF24 after thawing and centrifugation and removal of the cryoprecipitate.”
On June 23, 2023, FDA issued a guidance, for immediate implementation, Alternative Procedures for the Manufacture of Cold-Stored Platelets Intended for the Treatment of Active Bleeding when Conventional Platelets Are Not Available or Their Use Is Not Practical that permits blood establishments to adopt exceptions and alternatives to certain requirements to support the manufacture of cold-stored platelets (CSP) without submitting a variance request to the agency under 21 CFR 640.120. FDA noted that maintaining platelet availability in the face of logistical challenges (e.g., in military, prehospital or austere settings) or other threats to blood availability (e.g., mass casualty events or public health emergencies) is critical to assure that platelets are available to patients with active bleeding.
Until such information can be included in the next version of the Circular, blood establishments that manufacture CSP must update their December 2021 Circular to provide adequate directions for the use of CSP. FDA recommends including the following statements and information:
Package Inserts for the INTERCEPT Blood System for Platelets were revised to remove acute respiratory distress syndrome (ARDS) from the Warnings and Precaution section. ARDS remains described in the clinical summary section of the package inserts. Accordingly, blood centers manufacturing INTERCEPT-treated platelets may update their December 2021 Circular of Information to reflect this change.
On May 12, 2021, the FDA’s July 2018 Zika virus (ZIKV) Testing Guidance was withdrawn because the agency has determined that testing for ZIKV, or pathogen reduction as an alternative to testing for ZIKV, is not necessary to comply with the requirements of 21 CFR 610.40(a)(3) because ZIKV is no longer a Relevant Transfusion-Transmitted Infection (RTTI). FDA requires establishments to update the Circular at the time testing is discontinued and report the changes to your Circular “in the annual report under 21 CFR 601.12(d).”
Accordingly, the recommendation was not included in the December 2021 Circular. For Blood Centers that continue to have ZIKV tested units in their distributed inventory and to satisfy FDA’s expectations, AABB recommends adding this statement to your Circular at the time testing is discontinued:
“Blood components collected between [insert date-date] were tested with a licensed nucleic acid test (NAT) for Zika Virus RNA and found to be nonreactive.”
At the time your blood center no longer has ZIKV-tested units in your distributed inventory, you can opt to delete this statement from your Circular of Information.