REGULATORY UPDATE: Circular of Information Updated for Cryoprecipitated AHF Manufactured From PF24

AABB updated the Circular of Information web page this week to include new language required by the Food and Drug Administration for the manufacture of cryoprecipitated antihemophilic factor (AHF) manufactured from plasma frozen within 24 hours after phlebotomy (PF24).

It is important to refer to the FDA-approved use of the blood collection set described in the package insert and the regulations that apply to understand why it is necessary, under certain circumstances, to request FDA approval for an exception to those FDA requirements using the variance request process under 21 CFR 640.120.

Cryoprecipitated AHF is manufactured from plasma, as defined in 21 CFR 640.50 (a) and (b):

• FDA approves a blood collection set based on details in the manufacturer’s submission.
• The manufacturer’s submission specifies the intended use of the blood collection set for plasma preparation of FFP or for expanded use to prepare other plasma products.

FDA has confirmed that an approved variance is necessary in the following circumstances:

• Only when the facility intends to prepare other types of plasma, including cryoprecipitated AHF manufactured from PF24, using a collection set FDA-approved for plasma preparation of FFP only.
• To provide an FDA-approved alternative or exception to applicable regulations at 640.54(a)(2), which requires the plasma be “placed in the freezer within eight hours”, and 606.65(e), which requires the blood collection set “to be used in a manner consistent with instructions provided by the manufacturer.”

An FDA-approved variance is not necessary for cryoprecipitated AHF prepared from PF24 if using a blood collection set that is FDA-approved for use in preparing additional plasma products and not limited to FFP.

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.”

Those with questions may contact regulatory@aabb.org.