Regulation of Research Antibodies

James Stiehr jcim at pipeline.com
Mon Dec 12 10:58:38 EST 1994

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 US.

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:

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

However, if one were to classify analytes as the pending 
regulations suggest, the list of regulated antibodies will be 
much larger.  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 & 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?  

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 estimated 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 US 

What about products labeled "For Laboratory 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 

For a good review of this issue, please refer to the November 
15th issue of Genetic Engineering News [14(20):1].

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.  For 
questions or comments, please e-mail to jcim at pipeline.com

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