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Christina P. Liu cliu at IC.NET
Tue Apr 18 11:13:49 EST 1995

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Date: 17 Apr 1995 06:27:50 GMT
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The information in the following pages should be  

seen by all the department's scientists.

Please, distribute.

Electronic Posting Courtesy of  BIOALERT NEWS

BIOALERT NEWS   April 1995


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 
DNA/RNA probes.

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 
never enforced.

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 
officially responded.

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 
Medical Devices.

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 
controlling biologicals.

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

The text of this document  is not copyright. Feel free to copy 
and distribute.

 Please, help in the distribution of this information. Scientists 
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.

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