The Food and Drug Administration issued a highly anticipated final guidance this morning 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.
AABB Regulatory Affairs is currently preparing a toolkit to assist member facilities in implementing the final guidance. In addition, AABB will update the Circular of Information web page with FDA’s recommended statements and information for the use of CSP. Facilities with questions may contact regulatory@aabb.org.
What’s in the Guidance
FDA defines cold-stored platelets as those stored continuously at 1 to 6 degrees Celsius within a specified time after collection.
The director of FDA’s Center for Biologics Evaluation and Research has authority under 21 CFR 640.120(b) to issue a notice of exception or alternative to any requirement in 21 CFR parts 600-680 regarding blood, blood components or blood products if a variance under this section is necessary to assure that blood, blood components or blood products will be available in a specified location to address an urgent and immediate need.
To address the urgent and immediate need for platelets in the U.S, FDA has issued this final guidance for immediate implementation, giving notice of the following exceptions and alternatives under 21 CFR 640.120(b) now available to all blood establishments:
- Alternative procedures to 21 CFR 610.53(b) and 21 CFR 606.65(e) to permit the storage of apheresis platelets at 1 to 6 degrees Celsius for up to 14 days from the date of collection when such apheresis platelets are intended for the treatment of active bleeding when conventional platelets are not available or their use is not practical.
- Exceptions to the requirements in 21 CFR 640.25(b)(1) and 21 CFR 640.25(b)(3), regarding testing for platelet count and measurement of actual plasma volume, for the manufacture of apheresis platelets stored at 1 to 6 degrees Celsius for up to 14 days from the date of collection, and intended to treat active bleeding when conventional platelets are not available or their use is not practical.
In section III, “Notice of Exceptions or Alternatives,” FDA clarifies that blood establishments may adopt the above-listed exceptions and alternatives without submitting a request to FDA under
21 CFR 640.120(a). However, licensed establishments must report changes to their approved application as a CBE 30 in accordance with
21 CFR 601.12 as discussed in section V, “Reporting Implementation of Manufacturing and Labeling Changes.”
The final guidance also provides recommendations to blood establishments for the manufacture, process validation, quality control testing and labeling of CSP. Additionally, the guidance specifies the statements and information to be added to the Circular of Information to provide adequate directions for use of CSP.
Regarding the control of bacterial contamination of platelets, the guidance states that “cold storage of platelets as described in this guidance is an adequate method to assure the risk of bacterial contamination is adequately controlled.” Furthermore, establishments may consider implementing additional measures as described in FDA’s
December 2020 guidance on platelet bacterial risk control.
The agency stipulates that blood establishments that manufacture CSP must comply with all requirements that apply to platelets collected by automated methods, except for the alternative procedures and exceptions under 21 CFR 640.120(b) described in section III of the guidance. Collection of apheresis platelets and further processing (such as leukocyte reduction or pathogen reduction) must be performed in accordance with the device manufacturer’s instructions for use (21 CFR 606.65(e)), except for their instructions for the platelet storage temperature and dating period.
In addition, the final guidance discusses the need for additional data on the efficacy of CSP to address whether their use is supported when conventional platelets are available and whether their use is practical. FDA expects that the use of CSP manufactured under the alternative procedures and recommendations described in the guidance will generate real-world evidence to further inform regulatory decision-making on the storage conditions and dating periods for devices used in the manufacture of CSP. The agency will continue to assess the available data on the use of CSP to determine whether changes to the alternative procedures and recommendations described in this guidance are appropriate.
