IF YOU USE ANTIBODIES, YOU SHOULD READ THIS BULLETIN
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.
>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,
>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
>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
>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
>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
>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
>The text of this document is not copyright. Feel free to copy
> 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.
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