Darrell Pilling pillingd at bham.ac.uk
Mon Apr 17 09:38:41 EST 1995

In article <3mt1ha$kuh at slip-1.slip.net>, biotech at slip.net 
>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, 
>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 
>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 
>or  the antibodies be Classified as Class I.  As of  April 10, 
>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 
>conjugated to these tracers, and chromogenic substrates of 
>enzymes.  This ruling designates all of these as Class II 
>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 
>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 
>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 
>increase considerably. In the midst of this, the prevailing 
>position of the College of American Pathologists continues to 
>support their original request for these antibodies to be Class 
>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 
>to assess. The detrimental effect it may have on research could 
>be substantial and at this point it is difficult to predict if 
>gains of this new move will produce benefits commensurate to 
the loses 
>inflicted to research and indirectly to healthcare. In the mind 
>many it is difficult to answer, with certainty, the lingering 
>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. 
>should be aware of this pending problem.  If you have a 
>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.

I for one have no idea what a class I, II or for that matter III 
Medical Device is.  A brief explanation of what these 
classifications mean would be most helpful in understanding this 
obviously important matter.

Aarn Huissoon

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