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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
[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. 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@biddeford.com
Mia Schwierzke
BIODESIGN International
Phone (207) 985-1944
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