Awesome Variances “First break all the rules” Carolyn Te Young & Jed Gorlin ABC 7/04

Variances: An underused tool RIBC has been granted variances for: Tattoos: applied in licensed parlors Hemochromatosis: hct down to 34% ml using 500 ml bag- may use HIV WB indeterminate- case by case reinstatements following adverse lots HCV RIBA indeterminate-case by case

Exceptions and Alternatives approved under 21 CFR “The director for CBER may approve an exception or alternative procedure to any requirement in subchapter F (biologics) of Chapter 1(Parts ) of title 21 CFR. Both licensed and unlicensed establishments must submit requests: Guidance for Industry: Changes to an approved Application: July 2001)

Tattoos First applied to AABB for variance: Deferred by AABB Standards and TTD committee pending review by FDA. Granted by FDA for licensed parlors- limited to tattoos only, not other piercing Granted by AABB Standards July 2002 Single use needles AND pigments only

Hemochromatosis RIBC has standard variance allowing more frequent donations and not requiring labeling. BUT, they also were granted the ability to draw donors down to a hct of 34% provided the donation volume is between ml using the 500ml bag. Logic: RBC mass > than 405 ml from donor with 38% hct

ml: Short units In the event that less than 449 mls obtained from a donor with hct > 38%, but > 405 ml, then RIBC uses the unit as a regular unit, since the RBC mass exceeds that obtained from a standard draw using a 450 ml bag.

HIV-Western blot indeterminate MBC acts as confirmatory testing center for RIBC. MBC was using Calypte for HIV WB. Quality of HIV WB deteriorated significantly in , resulting in very high rate of unreadable or indeterminate WB. One time approval for re-entry of selected donors affected by these tests allowed.

Other one time donor variances For a few individuals with HCV reactive ab, indeterminate RIBA and negative singlet NAT testing, approval for re-entry of donor has been allowed.

Other approved variances 21 CFR (e) Use of NAT testing for other types of donors? Use of EIA testing for specimens with high fat 21 CFR Ship autologous blood untested (test subsequent unit) 21 CFR 640.4, : Allow use of components exposed to temperatures up to 17C up to 2 hours and 15 minutes.

Other approved variances (cont.) 21 CFR Allow syphilis testing on substitute sample drawn 1 day later 21 CFR a Allow use of 325 RBC exposed to 1 to –3oC for up to 4 hours provided each unit examined for hemolysis! 21CFR Allow use of A and AB FFP warmed to –4C over an 18 hour period with consignee notification. Also allow FFP manufacture when frozen within 24 hours after collection.

Ortho Hepatitis B sAg system 3 This “new improved, more sensitive test” also had up to 10 fold more false positives! Pending switch to alternative test, blood centers may apply for a one time variance to have falsely deferred donors reinstated after negative BioRad test. (UBS (+ others?) currently offering this reinstatement pathway testing)

HCT variance for plateletpheresis MBC will apply for variance to allow platelet collections from donors with 36% hct. Current machines lose few RBC if procedure halted. European rules allow platelet donations at a lower hct. Machines validated for use with lower hcts. Beth Israel in Boston (Transfusion report?) previously published efficacy of this variance.