Eman

Current employer has been using Chloraprep for years, with a small number of the povidone-iodine combo scrubs available for the rare donor with an allergy to chloraprep (I think that's super rare but have no data, but I know we've had event reports about expired PI swabs being available). My prior employer, 2004-2011, also used Chloraprep exclusively (although probably not in 2004, I don't recall exactly when Chloraprep became available). I have always had a good impression of the chloraprep scrubs.

Ah, you are correct, its a bit vague, but we treated it like a strong recommendation and only made RBCs from whole blood that took longer than 20' to collect.

There's a comment in the Technical Manual about not making cryo from units that take more than 15-20 minutes to collect, the organizations I've been have used that guideline to determine manufacturing. As well as the no clots part of course

I think we would refer to this statement in our "Organization" Quality Program document: The Quality Unit responsibilities are defined and include: active and prospective participation in quality planning; oversight of all activities relating to quality; ensuring that policies and procedures are properly maintained and executed; ensuring that the quality of products, tests, and services provided conform to regulatory/accreditation, customer, and company standards; and maintenance of the facility quality manual

Hi, I can only answer some of your questions: We have had a Trauma WB protocol in place for a while. Below are our use restrictions, we generally only have 2-6 of these products available, so most recipients do get switched to RBCs after the initial WB transfusion(s). These are not crossmatched, being for trauma situations only, and are in fact issued on back up and reconciled in the LIS afterwards. Since we limit it to two products until the patient is typed, and they wouldn't get a group O after an incompatibility is identified, I don't believe we've had any typing issues subsequent to the WB transfusion. Seems like mixed field could be a confounder though. • Product Use: o Limited to adult patients weighing 40 kg or more o Untyped recipients will not receive more than two of these units. o Women of child bearing age and individuals with unknown Rh type will receive Rh negative products. o Adult males and women not of childbearing potential (55 years of age and older) will receive Rh positive products. A lot of these products went unused at first, but use picked up in the 2nd year of the program (I think we're in year 3 now)

FWIW, we give our Trauma WB products a two week expiration date, because of the declining platelet function.

When we were bringing up a platelet collection system I asked the manufacturer some questions about the bag volume limits (100-400mL) and time spent where the volume was greater than 400mL. This scenario occurs for example when a 500mL intended-double is collected, but stored in one bag until counting/processing begins after the collection. That manufacturer said you could go up to 24 hours "out of range" before you compromised the product. Similar concerns about the storage concentration, the manufacturer has validated an acceptable platelet concentration range, odds are your volume reduction process results in a concentration greater than their validated upper limit. With your closed system scenario I'd be uncomfortable giving the volume reduced product more than 24 hours without having validation data showing viability past that point. Due to container, volume and [PLT] concerns. At a previous employer we volume reduced platelets and they were pretty ugly products, my current employer no longer volume reduces platelets, we give multiple divided aliquots instead. [sorry for reiterating some of the points made earlier. they're good points ]

We were using TempTales for quite a while, but "suddenly" had trouble getting some cooler validations to pass. That's when we realized that the TempTales had a fairly large +/- tolerance, too large when validating a 1-6°C range. So our transfusion service ordered up some LogTags, they've been very happy with those over the past couple years.

Your questions need a bit more context I think, not really sure if you're talking transfusion service or blood center. But maybe this will help. 1) In a US blood center setting, when processing freshly collected whole blood into RBCs and a plasma product, a second spin is typically allowed if there is blood in the ports (which means that blood would go through the port into the plasma bag) or poor RBC/Plasma separation. Typically you'd clear the ports, gently remix the WB a bit and then respin. Additional WB spins are not allowed. The centrifuge settings should be validated for your WB processing and you shouldn't see reddish plasma too often. 2) We leukoreduce before the WB is separated into RBCs and Plasma, and bedside filters are standard. So not sure what you mean about the filter step. Washing and irradiating could be done in either order, but sometimes your computer system may define your process (for a while at my current employer you had to irradiate before washing because our computer system wasn't set up to allow you to wash and then irradiate, that modification path wasn't defined in the computer system). Washing shortens your outdate drastically while irradiation only reduces it to 4 weeks or the existing expiration date if shorter, so irradiating first might make more sense. 3) If you don't use a sterile connection device during your cryo production you've got an open system, and remember that freezing doesn't actually destroy any introduced bacteria. If you are making pooled cryo, using an open system shortens your thawed shelf life from six hours to four hours, but if you sterile dock during that process you get six hours. I'm not actually sure about single cryo units, you probably still have the four shelf life on that product after thawing. (and if you make open system single units and then pool you'll only get the four hour shelf life even if you do sterile dock during pooling). Closed system for making singles and pooling is pretty much the standard practice.

Fair question, I'm sure it depends on if the manufacturer makes the claim or not. Cerus is the only licensed PRT provider/system in the US and their package insert states it will "potentially reduce the risk of TA-GVHD." Not as strong a statement as I expected, but our medical leadership has taken it to heart. Perhaps we will see a case report in a few years, hopefully not!

The folks handling BPDRs are different people than the inspectors, I don't think anyone does both. My/our groups interactions with BPDR submissions have been very positive, sometimes we're told it's not actually reportable, sometimes they tell us they changed the classification code. I've also had positive interactions writing in to ask if a situation is reportable (I switched from QA support of BBTS to HCTP a year or so ago, so have had a LOT of questions. Rather different on the HCTP side).

Curious what you mean, the pathogen reduction (PRT) is FDA cleared and accepted to replace irradiation due to GVHD concerns. Prior to implementing that our platelets were 100% irradiated, just to be safe. There is a rWBC threshold for the PRT process, we still do QC on rWBC on the platelets to make sure we're lower than the limit. And RBCs get irradiated when patient needs indicate. But totally agree that LR filters do not remove 100% of WBCs, and since it's not 100% tested some over the limit may slip through. More of concern with RBCs though, which are irradiated as needed. The apheresis tech is pretty reliable when it comes to LR.

There's an annual BPDR summary for BB/TS from the FDA, looks like 2016 is the most recent available at: https://www.fda.gov/BiologicsBloodVaccines/SafetyAvailability/ReportaProblem/BiologicalProductDeviations/ucm129757.htm 1,956 BPDRs from Transfusion Services in 2016, a majority being QC and distribution related, not documenting issue in the computer system is typically the #1 reason.

I guess I could clarify that our validation environment (and training environment) is identical to the live production environment, except the "other" two environments don't interface to billing.

I know we have users from multiple countries here, another confounding point is that the US considers leukoreduction to have less than 5*10^6 WBCs left, but the EU standard is less than 1*10^ WBCs in the product. One nice thing about having implemented pathogen reduction for platelets is we can stop irradiating for GVHD, since the pathogen reduction also stops WBCs from being able to reproduce (the platelet products are still coming off the machine leukoreduced too).

Doesn't seem extreme to us at all, we also enter PT specimens into our LIS, although we use the validation environment to keep fake patients out of the live side, which also means we don't get billing issues with these. By managing the PT specimens in the LIS we are truly treating them like real patient specimens.

If you're registered with FDA you ought to update your address with them, since your address is part of the registration record.

I suspect there will be some regional bias after mentioning AABB That said, I'm in the Midwest and have been impressed by the Wisconsin Association of Blood Banks annual meeting (disclosure: I used to chair their Education Committee and since leaving WI have been back as a presenter twice in the past 6 years). There's is a 2 day conference with a fairly large vendor area/participation. www.wabb.org

Neil is correct, there was some kind of regulatory change around 5-10 years ago so 5 day Thawed Plasma is legal now, no variances required. [I think the change was officially recognizing the 5 day product.] Also agree that validation of the plasma contents is not required, just validate your computer/label processes. Our frozen product is immediately relabeled as E2720 (Plasma, thawed, CP2D) upon thawing, given the 5 day expiration right away.

Here's another useful paper, it was the model for the study reported above (and they had a bit better FVII retention). http://onlinelibrary.wiley.com/doi/10.1046/j.1537-2995.2001.41040570.x/full Serial measurement of clotting factors in thawed plasma stored for 5 days Authors Katharine A. Downes MD, Erica Wilson MD, Roslyn Yomtovian MD, Ravindra Sarode MD First published: April 2001 able 1. Mean coagulation factor levels at 24-hour intervals by blood group Level* Coagulation factor Day 1 Day 2 Day 3 Day 4 Day 5 Mean change from Day 1 to Day 5 (%) p values * Mean ± SD. † Comparison of FVIII activity at Day 1 and that at Day 3 was statistically significant. FVIII (%) Blood group A 107 ± 26 76 ± 19 66 ± 18 65 ± 17 63 ± 16 41 <0.004† Blood group B 103 ± 44 74 ± 37 71 ± 35 67 ± 36 67 ± 33 35 <0.02† Blood group O 70 ± 16 51 ± 10 43 ± 10 43 ± 7 41 ± 8 41 <0.001† Factor II (%) 81 ± 9 81 ± 9 81 ± 9 80 ± 10 80 ± 10 1 NS Factor V (%) 79 ± 7 75 ± 8 71 ± 9 68 ± 9 66 ± 9 16 NS Factor VII (%) 90 ± 18 81 ± 15 76 ± 15 72 ± 14 72 ± 15 20 NS Factor X 85 ± 13 84 ± 13 84 ± 15 82 ± 11 80 ± 11 6 NS Fibrinogen (mg/dL) 225 ± 12 224 ± 13 224 ± 13 224 ± 17 225 ± 12 0 NS

Both the Technical Manual and Circular of Information include a table from a paper published a while back (2009) showing how the various factor and proteins C and S and anti-thrombin persist (or not) over 5 days. It's really not pretty but here is a copy/paste from the circular of information, which is also available from AABB (direct link, go to page 14 for easier reading of the table) I do QA and software support now, so read your question as about validating the computer/labeling process. Our facility skips the 24 hour FFP step, so when we thaw a plasma it is immediately re-labeled as 5 day Thawed Plasma [looks like our study results might not have passed at Kate's place, only about 70% of FVII remained after 5 days at 1-6 in FFP, but the FP24 would pass (it started lower but retained 86% of activity).] Table 3a. Coagulation Factor Activity in FFP and PF24 (whole blood) at the Time of Thaw and after 120 Hours of 1 to 6 C Storage (adapted from Table 1. Scott EA, et al. Transfusion 2009;49:1584-91) Thaw, mean ± SD (range) by product 120 hr, mean (range) by product %Change after 120 hr at 1 to 6 C Analyte FFP (n=20) PF24 (n=14)* FFP (n=20) PF24 (n=14)* FFP PF24 FII (IU/dL) 97 ± 10 (83-125) 97 ± 8 (80-113) 95 ± 10 (82-126) 96 ± 11 (74-120) 3‡ 1 FV (U/dL) 85 ± 13 (63-104) 86 ± 16 (54-124) 67 ± 19 (17-92) 59 ± 22 (15-109) 21‡ 31‡ FVII (IU/dL) 105 ± 25 (50-163) 89 ± 22 (54-145) 70 ± 18 (34-102) 77 ± 27 (50-159) 33‡ 14‡ FVIII (IU/dL)§ 81 ± 19 (47-117) 66 ± 17 (30-100)† 43 ± 10 (27-60) 48 ± 12 (26-73) 47‡ 28‡ F IX (IU/dL) 82 ± 13 (62-108) 88 ± 13 (70-105) 80 ± 12 (64-107) 84 ± 12 (65-99) 2 4‡ FX (IU/dL) 94 ± 10 (71-112) 94 ± 11 (72-112) 87 ± 11 (65-111) 91 ± 12 (67-114) 7‡ 3‡ vWF:Ag (IU/dL)§ 98 ± 27 (57-156) 132 ± 41 (78-211) 97 ± 30 (48-150) 127 ± 40 (79-224) 1 4 vWF:RCo (IU/dL)§ 101 ± 26 (61-152) 123 ± 47 (58-238) 93 ± 30 (48-149) 102 ± 38 (50-191) 8‡ 17‡ Fibrinogen (mg/dL) 280 ± 52 (223-455) 309 ± 70 (211-500) 278 ± 50 (223-455) 303 ± 50 (205-490) 1 2‡ Anti-thrombin (IU/dL) 97 ± 9 (85-118) 97 ± 11 (77-110) 100 ± 10 (85-131) 101 ± 14 (73-116) 3 4‡ Protein C (IU/dL) 107 ± 20 (74-148) 88 ± 16 (65-120)† 107 ± 19 (77-148) 89 ± 17 (65-115)† 0 2 Protein S (IU/dL) 97 ± 18 (61-123) 92 ± 18 (54-121) 90 ± 22 (52-134) 78 ± 19 (46-114)† 7‡ 15‡ *N = 25 for FII, FV, FVIII, Fibrinogen, vWF:RCo, and Protein S. †p < 0.05 compared with mean activity in FFP of the same age. ‡p < 0.05 when comparing mean activity at thaw to mean activity after 120 hours of 1 to 6 C storage. §Only results from group O products were used for statistical comparisons of factor VIII, vWF:Ag, and vWF:RCo activities.

Another important difference, at least in the US, is that INTERCEPT is approved/licensed for use with platelets and plasma but approval to use Mirasol in the U.S. is still pending (The Terumo website says Mirasol is "available in select markets". We went live with INTERCEPT for platelets earlier this year, been a generally positive experience. Downsides have been mostly related to collection targets (there are somewhat strict acceptance parameters for volume, platelet concentration and platelet content that required us to tweak our collection targets a fair bit) and the system isn't licensed for triple products, so we can only collect and process single and double collections. We had previously irradiated all of our platelets, so it was a nice benefit to no longer have to irradiate once we implemented INTERCEPT.

Nice work, congrats! When I was doing my SBB training our reference lab manager/educator had an running bet, she'd buy dinner for any student that took an SBB exam and didn't get a question about anti-D,C and G. Don't think she has bought anyone dinner yet

We use 55, like others have said 50 seems more reasonable to me.

Not sure what you mean by "ref kit" but we are currently collecting platelets on the Trima and getting ready to collect plasma with it. I forget if the plasma kit has 4 or 5 satellite bags but I think our intent is to collect 600-800/1000mL per donor (as allowed by their total blood volume and whether there are 4 or 5 bags), creating 200 mL aliquots. Helpful hint: assign a 28 day minimum interval for your plasmapheresis collections so you don't fall under the frequent plasma collection requirements.