Proposed FDA Antibody Regs May Affect You

biodesin at biddeford.com biodesin at biddeford.com
Tue Apr 4 15:58:17 EST 1995


I wanted to bring to the attention of the biological 
research community recent developments which will likely 
have the effect of curtailing the availability of 
monoclonal and polyclonal antibodies in the U.S.

The FDA is considering the enactment of regulations which 
would require regulatory submission and approval as an in 
vitro diagnostic product of any antibody used in 
immunohistochemistry, monoclonal or polyclonal, which 
recognizes an antigen that may have clinical utility.  
Only antibodies which identify an analyte or class of 
analytes for which no clinical utility has been suggested, 
either by the manufacturer or in the published literature, 
will not be subject to FDA requirements.

What does all of this mean?  That only antibodies whose 
sales justify the costs of these regulations (conservative 
estimates of $23,000 - $40,000 for a 510(k) submission in 
addition to ongoing compliance costs and liability 
insurance costs of an in vitro diagnostic product) will be 
offered for sale.  If the market for a new product is 
uncertain and the manufacturer believes that it will fall 
under FDA regulation - will that antibody ever make it to 
market?  Maybe not.  Will the cost of antibodies go up 
because of this?  Certainly.

Specifically, what antibodies will be required to undergo 
regulatory submission?  With such an ambiguous definition, 
the list could be very broad.  There are numerous analytes 
which are most likely to attract regulatory attention.  
Among others, this list includes (but is not limited to):

Actin, Calcitonin, Numerous CD antigens, Desmin, Ki-67, 
S100, Somatostatin, Cytokeratins and Vimentin.

However, if one were to classify analytes as the pending 
regulations suggest, the list of regulated antibodies will 
be much larger.  In fact, based on the recent FDA "Points 
To Consider" document, the regulations include secondary 
reagents, with further regulations existing for antibodies 
for flow-cytometry and molecular probes.

Consider what it means to have an analyte which MAY have 
clinical utility as an in vitro diagnostic product.  A 
list of analytes which meet this definition has been 
compiled by a pathologist and includes such proteins as 
bcl-2, p53, cathepsin-D, S-100 and tubulin.  Also consider 
the difficulty in interpreting such regulations.  When 
does an analyte go from having no clinical significance to 
being clinically significant?  Where is that line, and 
when is it crossed?  After one published suggestion of 
clinical utility?  10?  50?  A single published paper has 
often been the basis for regulatory action.  Yet, we 
believe it to be the pathologist who should define 
clinical utility, not the manufacturer or FDA.

Is this just the problem of antibody suppliers?  No.  
These regulations will effect the supply of research 
reagents available to the biological research community in 
the US.  One leading antibody supplier has established 
that the sales of 60% of their products would not justify 
the costs of submission and could potentially be withdrawn 
from the market.  This applies to the US only, so 
researchers in other countries will have access to a host 
of reagents which will be off limits to U.S. researchers.  
Another major supplier of IHC antibodies has vowed to 
withdraw completely from the U.S. market, should a Class 
II designation be given to these products.

What about products labeled "For Laboratory or Research 
Use Only"?  It doesn't matter that a company label or 
otherwise promote that an antibody be used for laboratory 
use and not for diagnostic purposes.  The regulations 
don't address the situation of pathologists employing 
unclassified reagents in their diagnosis.  Instead, the 
proposed regulations' effect is to prevent suspected 
improper use by physicians by removing unapproved reagents 
from the market.  There is no provision in the regulations 
to sell antibodies not approved for in vitro diagnostic 
use to the research community if they recognize analytes 
that may, now or in the future have clinical significance.

For a good review of this issue, please refer to the 
November 15th issue of Genetic Engineering News 

A thorough and spirited discussion is called for about 
this issue as it will have a real impact on the research 
being done in U.S. universities, government labs, and 
teaching hospitals.  JCIM, the Joint Council of 
Immunohistochemical Manufacturers, is continuing to work 
with the FDA to moderate the effects of the proposed 
regulation.  Expression of your viewpoints and interaction 
with JCIM and FDA toward a reasonable resolution of this 
matter are encouraged.  For questions or comments, please 
Email to biodesin at biddeford.com

Mia Schwierzke
BIODESIGN International
Phone (207) 985-1944
Fax (207) 985-6322

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