REGULATORY UPDATE: FDA Updates List of Variance Approvals

The Food and Drug Administration’s Center for Biologics Evaluation and Research (CBER) recently updated the list of exceptions and alternative procedures approved under 21 CFR 640.120 for July to December 2022.

FDA approved an exception to 606.65(e) and 610.53(b) to manufacture apheresis platelets, leukocytes reduced, stored at 1-6 degrees Celsius for up to 14 days without agitation. “The cold stored platelets products will be used to treat actively bleeding patients through day 14 of storage when conventional platelet products are unavailable, or their use is not practical.”

FDA continues to approve exceptions to 21 CFR 640.54(a)(2) and 21 CFR 606.65(e) to manufacture cryoprecipitated AHF and pooled cryoprecipitated AHF from plasma frozen within 24 hours after phlebotomy (PF24).

The agency also included five one-time exceptions:

• To 606.65(e) to distribute red blood cells, leukocytes reduced, fresh frozen plasma and recovered frozen plasma units that were collected from donors whose hemoglobin was determined using expired microcuvettes.
• To 610.53(b) and 640.34(b) to distribute for non-injectable use, frozen blood products (fresh frozen plasma, pooled cryoprecipitated AHF) that were exposed to temperatures warmer than -18 degrees Celsius for approximately 9.5 hours with the warmest temperature reaching 15 degrees Celsius, provided certain conditions are met.
• To 630.15(b)(iii) to distribute a rare source plasma unit collected from a donor with systemic lupus erythematosus (SLE) for which a new medical history and physical examination was not conducted.
• To 630.30(b)(1) and 640.65(b)(1)(i) to distribute source plasma units collected from donors who did not have a serum protein electrophoresis (SPE) and serological test for syphilis (STS) sample collected for testing on the day of their initial physical exam or plasmapheresis, provided that the implicated source plasma units are released as follows:
  
  

  (1) Units collected from donors who had a follow-up SPE/STS test with acceptable results may be released for further manufacture into injectable products; and

  (2) Units collected from donors who did not have a follow-up SPE/STS test may only be released for further manufacture into non-injectable products.

• To 640.76(a)(1) to allow source plasma units intended for further manufacturing into injectable products exposed to more than one episode of temperature fluctuations warmer than -20 degrees Celsius and colder than +10 degrees Celsius for approximately 19 hours and 55 minutes to not be relabeled as “source plasma salvaged,” provided the units remained frozen solid and the consignee is notified of the temperature deviations.

AABB encourages members to review CBER’s list of exceptions and alternative procedures to identify new options that might be useful in their facility’s policies and operations. Members with additional questions may contact regulatory@aabb.org.