Circular of Information for the Use of Human Blood and Blood Components

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 regulatory@aabb.org.

FDA's Formal Acceptance and Expectation for Proper Use of the December 2021 Circular

On March 22, 2022 FDA issued guidance formally recognizing the December 2021 Circular as an “extension of labeling” which provides specific instructions for the administration and use of blood and blood components intended for transfusion as required in 21 CFR 606.122.
The Circular is a controlled document and must not be revised. Once revised by a facility, the document is no longer recognized by FDA and must be resubmitted to FDA for review.
The designated pages at the front of the Circular permit the addition of facility specific information and FDA required updates in these defined areas only. Additions in these defined areas only are not revisions to the Circular.
The Circular must be available for review by Transfusion Services, prescribing physicians, and staff anywhere blood is issued or transfused. If the environment includes blood transfusion, the Circular should be available.
During the 2017 Ask the FDA session and again in 2021, FDA stated, “the availability of a hard copy Circular should be part of the overall distribution process, in accordance with §606.122, to include distribution on a yearly basis or whenever a change is made to the Circular, or upon request from your customers.”
As provided above, FDA has clarified their expectations for use of a hard copy with no expressed prohibition on the addition of an electronic version. An electronic version of the Circular has been developed and approved by the Circular Task Force to supplement distribution of the hard copy.

User Guide for the December 2021 Circular

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:

Whole Blood Section
Information on Bacterial Risk Control Strategies for Platelets
Expanded information on Pathogen Reduction Technology
Pathogen Reduced Cryoprecipitated Fibrinogen Complex Section

Purchase

Please visit the AABB Store to order the current Circular of Information for the Use of Human Blood and Blood Components, dated December 2021, as a hard copy brochure or brochure/electronic bundle.

View Posted 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.

FDA Required Updates to the Circular

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:

Using an adhesive label or an ink stamp to insert additional language into the 2 blank pages prior to the Table of Contents of the hard copy version of the Circular.
Updates to the eCircular be added to the 2 blank pages prior to the Table of Contents of the eCircular, similar to the hard copy version. The FDA required updates and approved language may be added to the large, editable text boxes on the designated pages.
Contacting your FDA Consumer Safety Officer before making any other changes to the content of the Circular.

NOTE: The version date of December 2021 for the Circular must not be changed.

Manufacture of Cryoprecipitated AHF from Plasma Frozen Within 24 Hours After Phlebotomy (PF24)

Background

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.”

Alternative Procedures for the Manufacture of Cold-Stored Platelets

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:

“CSP are intended for the treatment of active bleeding when conventional platelets are not available, or their use is not practical.”
“CSP must be stored continuously at 1-6°C to control the risk of bacterial contamination for up to 14 days.”
“Transfusion services should establish procedures for examining CSP for visible aggregates before transfusion.”

Pathogen Reduction Technology - Update to Warnings and Precautions for INTERCEPT-treated platelets

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.

FDA does not require this change until the next revision to the Circular is released.
Until this can be removed in the next version of the Circular, AABB recommends adding this statement to update your December 2021 Circular if you manufacture INTERCEPT-treated platelets:

“The package inserts for INTERCEPT Blood System for Platelets no longer include acute respiratory distress syndrome in the warnings and precaution section. Users should refer to the package inserts for information on adverse events observed in clinical studies of INTERCEPT platelets.”

Licensed establishments that choose to make this change must report it to FDA in their next annual report.

ZIKV Testing Language Update

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.