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
researchers.
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
significance.
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
