FDA Finalizes Guidance on Buffy Coat Method for Blood Component Manufacturing

The Food and Drug Administration released final guidance today on the development of blood collection, processing and storage systems for manufacturing blood components using the buffy coat (BC) method.

The agency said it made several clarifying edits in response to comments on the October 2024 draft guidance, including issues raised by AABB and the American Red Cross in joint comments.

The final guidance retains the core technical framework of the draft guidance while adding several substantive provisions, particularly around overnight whole blood holds, DEHP-free systems, platelet comparability studies, RBC hemolysis and implementation by blood establishments.

Most notably, FDA now recognizes systems that hold whole blood for up to 24 hours before component separation and states that the cited component regulations do not restrict the timeframe for separation from whole blood. The timeframe must instead be specified in the system's directions for use, with manufacturers expected to submit supporting data; the agency cites 4, 8 and 24 hours as examples.

The guidance also replaces the draft's recommendation to consider FDA-approved solutions with language supporting development of DEHP-free systems and additive solutions not currently approved by FDA.

For platelet comparability studies, FDA retains its recommended benchmarks and sample size of at least 60 units or pools in each arm but allows manufacturers to propose an alternative, statistically sound sample size with supporting data. The final also provides additional direction on control selection, including justification for the selected control or use of historical control data.

For RBC hemolysis, the acceptance criterion remains less than or equal to 1% hemolysis at the end of storage, but the agency now recognizes that donor-related factors may contribute to failures. The guidance states that such failures should be investigated and described in the submission, and FDA will consider identified reasons for failure during its review.

Once appropriate BC systems are FDA approved or cleared, licensed blood establishments could submit BLA supplements to implement manufacture of blood components using the method.