Validating a procedure not sanctioned by vendor

[Karrieb61]

Hi all, this goes along with my BBTalk post on running pre-warmed plasma on the Echo. Immucor does not say this is OK to do. I know that many of us run cold screens and panels using reagents that have not been 'sanctioned" to use at 5 or 15 degrees so we are using products off-label at least for this.

 

I am wondering if anyone can quote an FDA-CFR or other agency standard that tells us we can't run a test that we have validated on our own (method comparison kind of validation) but which the manufacturer has not sanctioned, blessed, validated themselves, whatever? This might apply for pre-warmed plasma run by tube also, I haven't checked that yet. Hope this makes sense, thanks

[Dansket]

For Gel users, the FDA has stated that a crossmatch done with an Anti-IgG Gel card cannot be used to demonstrate ABO compatibility, that an immediate-spin (gel or tube) must be done in addition to the IgG crossmatch. When ORTHO submitted the Anti-IgG Gel card to the FDA, the submission did not include data for the detection of ABO incompatiblity. Several papers have been reported at the AABB Annual Meeting that provide some evidence that the IgG gel card does detect ABO incompatiblity. I see some similarities between this and your situation. Just got off the phone with ORTHO Technical Services and they confirmed that legally IgG gel card may not be used to detect ABO incompatible by crossmatch.

[David Saikin]

Agree with Dansket on the IgG card and ABO - the Feds have made that a mandatory thing regardless if we have validated that the IgG card does detect ABO incompatibility. 

 

I am never averse to attempting off-label use of certain reagents based on info I've read in various journals, notably Transfusion.  I have (or am in the process) of validating anything I use of this nature.  Notably for me was the use of PeG autoabsorption after reading in Transfusion in 1999.  Now the Tech Manual has a procedure but I continue to use the one I validated based on the journal article.  Another which I have in the process is dealing with weak IgG gel abs and using Peg/plasma in tubes but adding a washed aliquot to and spinning in an IgG gel card instead of tube anti-IgG (also read about this in Transfusion). 

 

Your Medical Director needs to be comfortable with any "off label" uses you decide to investigate or use.

[Karrieb61]

I did just find an excerpt froma 2012 article in the American Journal of Clin Path that said that "CLIA allows clin labs to modify FDA-approved tests (so called off label use) to develop their own tests as long as they follow the requirements to validate the performance characteristics of the lab developed test. There were no references cited from what I could see but it does sound like as long as we validate that putting warmed plasma on the Echo doesn't negatively affect expected results (loss of significant antibodies for example) then we might be OK.

[goodchild]

Do you have a healthy supply of patients who have cold autoantibodies and underlying clinically significant antibodies with which to validate your proposal?

[tbostock]

Careful though, when there are documented studies that show that warming does diminish some clinically significant antibodies.

 

• Mallory, D: Controversies in transfusion medicine. Prewarmed tests: pro - why, when, and how - not if. Transfusion 1995 35: 268-270.
• Judd, WJ: Controversies in transfusion medicine. Prewarmed tests: con. Transfusion 1995 35: 271-275. 

[Karrieb61]

Thanks tbostock, I did read that here previously so I am trying to be very cautious in how we do this. At the moment, I am telling the techs that if the  cold is very strong, (4+) in tube, then they can pre-warm the plasma up to 30 minutes before running it on the Echo. I am mindful that warming has its issues. And yes Goodchild, we have a fair number of known colds that we will continue to use to validate this before I make it official. Lots of fun, especially for the techs who think that pre-warming for 60 + minutes (like they used to do) is the answer to all problematic antibody IDs. The flack I am getting back from that small group is ridiculous. The lack of immediate transfusion reactions is their comeback of course, no worries on their part about a potential delayed reaction or a full blown antibody discovered later. .....

[Auntie-D]

Gel isn't validated for ABO as it detects IgG not IgM - it is perfectly possible to have an incompatible crossmatch come up negative. Immediate spin must always be done to confirm ABO compatibilitiy on first presentation (computer compatibility is fine after that). But for a full crossmatch I always recommend doing a spin crossmatch as there's nothing worse than booking the units into the computer after the crommatch (which was comaptible) is complete and you find you have grabbed the wrong group and have to start again. I have never done this but have seen others do it on two occasions...

[Eagle Eye]

How about reserving a unit in computer before proceeding for IgG gel crossmatch?

In other words reserve a unit in your computer system which is able to flag ABO incomatibility then proceed with IgG crossmatch...