The information in the following pages should be
seen by all the department's scientists.
Electronic Posting Courtesy of BIOALERT NEWS
BIOALERT NEWS April 1995
THE FDA ABOUT TO CONTROL ANTIBODIES
The Federal Drug Administration, FDA, is nearing its plans
to implement a new antibody classification ruling which will
designate numerous antibodies as Class II Medical Devices.
Many believe that this new regulatory action will have major
repercussions in nearly every branch of biological and medical
research. The FDA has started with the regulation of antibodies
used for immunohistochemistry, but there are good indications
to believe that this will expand to cover Flow Cytometry,
Hematology, Cytology and even Molecular Biology including
The classification of primary antibodies as Class II Medical
Devices was the result of a reclassification petition by the
College of American Pathologists (CAP).The meeting of the
Hematology and Pathology Devices Panel, was held in
Gaithersburg, MD, on October 21, 1994. According to
previous FDA rules, these antibodies by default were placed
in Class III status. However, this was more a provisional
status than a real Device classification, and consequently
During the Classification Panel meeting the CAP group
corroborated their support for Class II as they had previously
petitioned. At least five other groups including a dissident
group of Immunopathologists within CAP itself, took a
position contrary to that of CAP and supported Class I
designation. The Joint Council of Immunohistochemistry
Manufacturers (JCIM), representing the manufacturers,
also supported Class I designation. The JCIM position was
also supported by The Health Industry Manufacturers
Association (HIMA), the largest association of the health
industry with a membership in excess of 700 health care
companies. At the end of the meeting, the official group of
CAP obtained a victory, and all primary antibodies having
clinical application for Immunohistochemistry were
recommended to become Class II Medical Devices.
No provisions were made to permit the availability of
these antibodies for research use.
The Panel Classification Meeting of October 21, 1994,
was conducted in an unconventional manner. Apparently,
during the course of the meeting, the opinions of the
delegates of JCIM were suppressed to the extreme that their
position paper was not distributed to the Panel members.
Furthermore, the manufacturers presentation was kept under
strict time control and the manufacturers were not allowed
to respond to the arguments of CAP. In contrast, the CAP
representation, advocating in favor of Class II, were given
unlimited time for delivering their position and for general
discussions. This oppressive manner of conducting the meeting
as well as several other irregularities of the meeting, prompted
the filing of a complaint to the FDA by the Washington law
firm of Hyman, Phelps & McNamara, P.C,. on behalf of the
oppressed parties. Attorney Jeffrey Gibbs, in his complaint filed
with the FDA on January 9, 1995, lists the irregularities, and
cites the rules violated during the meeting. The complaint
reveals that the FDA officers present during the meeting
did not clarify to the members of CAP and the Panel members
that the requirements of safety and special controls they were
pursuing to accomplish by obtaining Class II could have been
implemented even if the antibodies were designated Class I.
Essentially, The College of American Pathologists and the
Panel members were misled by the FDA into believing
that their goals were only possible if Class II was designated.
In the complaint, Mr. Gibbs requested that the recommendations
of the Panel Meeting be invalidated, the meeting be rescheduled,
or the antibodies be Classified as Class I. As of April 10, 1995,
three months after receiving the complaint, the FDA has not
The significance of the outcome of this regulatory petition
spearheaded by the College of American Pathologists is that,
if designated as Class II Medical Devices, an extensive list
of antibodies both polyclonal as well as monoclonal,
including CD markers, will be subjected to an expensive
process of Class II Medical Device approval.
The manufacturers as well as distributors of these antibodies
argue that the approval cost of these antibodies will most
likely be $20,000 to $30,000 per antibody. They believe
that approximately 90% of these antibodies do not produce
sufficient sales to justify an expenditure at such level.
It is thus believed that many of these antibodies will be
removed from availability in the U.S. In addition, all
manufacturers and many pathologists assert that these
antibodies, when used for immunohistochemistry, are of
low-risk to the public and should not merit the strict
regulatory environment of Class II Medical Devices.
An analysis of this ruling and comparison to the common
of Medical Devices controlling products used in Clinical
Laboratories, we find a major difference in the magnitude
of the scope of the new regulation:
In the case of devices for clinical labs, the complete
device is the center of the regulatory action. For example,
a kit like Hybritech's PSA is classified as a device. This
does not designate any antibody to PSA, monoclonal or
polyclonal, as a Medical Device. It is the complete kit,
the device, which is licensed under the approval process.
Therefore, the antibody by itself is not the device.
Consequently, antibodies to PSA can be made and sold
as antibodies without being an infraction to the FDA
regulations. The new ruling, however, is different because
it targets the antibodies themselves and gives no provision
for the supply of the antibodies outside of the ruling.
Under these new regulations, since the PSA antibody has
clinical significance for Immunohistochemistry, it becomes
itself a Medical Device. Similarly, many other antibodies
will be under the same set of rules.
In the last two versions of the Points to Consider, a document
published by the FDA as a guide to the requirements of this
ruling, they have unexpectedly included all auxiliary reagents
used in immunohistochemistry as Class II Medical Devices.
This was unanticipated since there was no mention or
discussion on this subject during the Panel Meeting held on
October 21, 1994. Since the classification Panel never ruled
on the auxiliary reagents, it is not understood their sudden
appearance in the Points to Consider documents.
The improprieties of this inclusion may be a separate issue
but the significance of this addition goes beyond anything
expected. These auxiliary reagents usually contain secondary
antibodies labeled with either biotin, peroxidase, alkaline
phosphatase as well as conjugates of avidin or streptavidin also
conjugated to these tracers, and chromogenic substrates of these
enzymes. This ruling designates all of these as Class II Medical
Devices. This remains an unassembled puzzle for the
manufacturers and many observers.
Overall, the amount of antibodies which may be added to this
list could be considerable. It will surely include most of the
CD antibodies available today as well as antibodies to tumor
markers, infectious agents, and practically any antibody of
general importance. This appears to be a heavy regulatory
weight over a broad range of products that are needed for
general research by the U.S. scientific community.
Both manufacturers as well as many users fear that this will
curtail research in the US and place US scientist at a disadvantage
in relation to their European and Japanese colleagues. Some
independent Pathologists are disheartened with the idea of
increased regulation and fear that the prices of the antibodies will
increase considerably. In the midst of this, the prevailing official
position of the College of American Pathologists continues to
support their original request for these antibodies to be Class II
Altogether, the scope of this new set of rulings led by what
appears to be a misled group of Pathologists, is a difficult matter
to assess. The detrimental effect it may have on research could
be substantial and at this point it is difficult to predict if the
gains of this new move will produce benefits commensurate to the loses
inflicted to research and indirectly to healthcare. In the mind of
many it is difficult to answer, with certainty, the lingering questions:
Is this necessary ? Is this really protecting the American public ?
Predictable is, that the FDA will continue in their pursuit of
Whether or not the scientific community will accept the future
limitations imposed to their work by the combined efforts and
ensuing victory of the College of American Pathologists and the
FDA, remains to be seen.
Ti H. Sllubon
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should be aware of this pending problem. If you have a computer
with telecommunication capabilities, download this document
and post it to any Life Sciences newsgroups including Medicine.
Post under the heading: IF YOU USE ANTIBODIES, READ THIS.....
If you get a hardcopy of this document, circulate to all
scientific staff at your institution.