ASR and FRO (RUO) reagents -Reply

From: CATHARINE FRITSCHI (CSFRITSC@SENTARA.com)
Date: Tue Jun 01 1999 - 17:32:30 EST


Some tidbits as I understand them (unfortunately, I am never brief).  This info
is for ALL CLINICAL Flow labs; you must add the required comment to your
reports, or else!     (what?  to be determined...)

Any reagent / application that is FDA approved needs no comment (i.e. our FDA
approved CD4 / CD8 reagents on peripheral blood).  Stop here if you only use
FDA approved reagents for clinical assays on peripheral blood.  The rest of
you...

Remember the letters that you had to sign promising that you were not using
"for research use only" reagents for clinical purposes?  The ASR reagent
category replaces that system and puts the burden of proving reactivity on the
labs for clinical assays.  

We attach the required comment (modified as indicated below) to all leuk
reports as no reagents I know of are FDA approved for doing leuk panels. 
(Please, someone, correct me if this is incorrect )    Also, I add it to
clinical results without FDA clearance i.e. our CD34 and HLA PRA screens.   

Becton Dickinson sent out a "bright-green" pamphlet explaining the ASR
regulations in pretty clear terms.  I even shared it with our special chem and
sendout labs as the original federal regulations are longer and more difficult
to interpret.  Call your BD rep to get a copy:  pub. # 11/98  23-3886-00.  Then
read the federal regulation.  The pamphlet also lists "for further reading"
articles.  Nice job, guys!

This is our modified version of the required comment:

"These tests were developed and their performance characteristics were
determined by the Sentara Norfolk General Hospital flow cytometry laboratory, a
CLIA-certified high complexity testing facility, using Class I Analyte Specific
Reagents (ASRs).  These tests have not been cleared or approved by the U.S.
FDA; Class I ASRs do not require FDA clearance or approval."

You must be a high complexity testing facility to use homebrew reagents for
clinical assays (homebrew = non-FDA approved assays = your leuk results).  See
CLIA regulations for high complexity testing requirements; your CAP inspection
may qualify for certification.  The last sentence is added to avoid
misinterpretation or refusal of payment by insurance companies "for research
use only".

We began this comment in December 98 and expected a huge resistance / response
from our clients.  I have yet to receive the first call.  I also worried that
this would jeopardize our market share with the competition.  But I figured
being shut down or having to scramble to fix it after being discovered, and
maybe even fined, would be worse.  We haven't lost any clients.

The vendors I contacted (Caltag, Coulter, BD) told me that the inserts have
been changed and that the labels on the reagent bottles have been changed.  As
their old-labelled stock is rotated off their shelves, I was told we would see
the new labelling.  

Reactivity of reagents without FDA approval which we are currently using have
been established through the years for leuks.  Any new reagents we begin using
will have to have their reactivity established.  I plan to place new reagents
in "quarantine", and run them on all specimens received to establish reactivity
and staining patterns.  I will have a separate folder for each new reagent
containing all titer info, histograms, and supporting literature pertaining to
this reagent.  Hmmm, but we all do this already, right?  These folders will be
very helpful when the lab is questioned or inspected.

Note:  "They" are not just picking on flow labs.  These regulations effect many
immuno tests using in-house antibodies or unestablished kit testing.  Our
institution even attaches comments to sendout results performed in reference
labs because the original testing was performed by someone else using ASRs.   

The only testing using ASRs that are exempt from adding a comment is
immunohistochemistry testing because, best as I can determine, the reactive
pattern must be reviewed by a pathologist together with morphology.  I called
20 antibody vendors in January for our IHC lab to document ASR policies, and
only 2 had even heard of ASRs.  I sent them the BD pamphlet info. 

Cheers!

Cathy Fritschi
Norfolk, VA



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