The Honorable Howard M. Metzenbaum
United States Senate
Washington, D.C. 20510
Dear Senator Metzenbaum:
This is in further response to your letter of July 24, 1990, on behalf of Ms. Virginia A. Luce, Springfield, Ohio, concerning the drug N-2 (also known as Sargenti Paste).The N-2 Sargenti Method of root canal therapy was introduced into this country in the early 1960’s. It was developed as a one- appointment root canal technique by Dr. Angelo Sargenti, Locarno, Switzerland. Although the drug has been on the European market for over 20 years, it has never been approved for use in this country. Proponents of this method have been advised repeatedly by this Agency that the N-2 material is considered to be an unapproved new drug, and may not legally be imported or distributed in interstate commerce until an applicant has submitted a new drug application (NDA) with convincing evidence of safety and effectiveness for the recommended use, and we have approved the application. A new drug application for this product was submitted by the AGSA Company in June 1962. The NDA was never approved and was finally withdrawn by the firm in July 1967. The Food and Drug Administration (FDA) continued in the ensuing years to receive complaints that similar products were being imported without approved NDAs. These complaints prompted the initiation of several field investigations, which revealed that the N-2 formulations were still being imported. In order to stop this practice, an import alert was issued to all FDA district offices in August 1971. This action denied entry to the N-2 formulations because they were regarded as new drugs with no approved NDAs in effect. It also resulted in the initiation of a voluntary recall of an N-2 type product in October 1971. Subsequent to this import ban, FDA received complaints that the formula was being promoted in this country through a scheme that involves referring dentists to local pharmacies to have the N-2 formula compounded under their prescription. Although the practices of dentistry and/or pharmacy properly are the responsibility of State and local authorities, our concern caused us to issue a letter to all State drug officials in April 1974, advising them that we regarded the N-2 preparations to be unapproved new drugs. The issuance of this letter to all the State agencies represented a major step on the part of FDA.
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In the mid-1970s, FDA began receiving another series of complaints concerning the availability of commercially manufactured N2 type formulas. We once again conducted extensive investigations concerning the latest promotion of the product. These investigations included a series of inspections, meetings with opponents of the drug, reviews of submitted data, and attendance at a lecture series given by the American Association of Endodontics on root-canal therapy. It became apparent that even if FDA were successful in eliminating from the interstate market all precompounded commercially marketed versions of N-2, a licensed practitioner may compound and dispense the Sargenti formula for individual patients under the practice of dentistry; customarily, such a practice would be subject to State and local jurisdictions. In this connection, some States, such as California, have informed the pharmacies operating within their jurisdictions that the N-2 formulations are considered new drugs and may not be dispensed even on the prescription of a licensed practitioner. After weighing these facts, the past history of these products, and the apparent acceptance of these formulations by a significant portion of the dental community, the Agency decided to carefully review the merits of the product before taking additional regulatory action. In particular, we wanted to be certain that a change of a violation of the new drug provisions of the Federal Food, Drug, and Cosmetic Act (Act) would stand scrutiny in a contested court case. We also wanted to evaluate whether additional actions (e.g., another letter to State authorities, a public Warning, etc.) should be considered. Accordingly, it seemed entirely appropriate to seek the advice of the dental and scientific community through our outside advisory committee. On November 12 and 13, 1975, FDA’s Dental Drug Products Advisory Committee convened and heard seven hours of testimony from individuals representing both sides of the controversy. After deliberation, the committee concluded and so advised that there was insufficient valid scientific evidence to permit a judgement that these preparations are generally recognized as safe and effective. The committee also found insufficient evidence of significant risk from use of the N-2 formulations themselves to warrant recommending their removal from the market. While the Agency agreed with the committee’s scientific judgement that N-2 formulations did not pose a significant hazard, we disagreed with the recommendation to permit continued marketing. The committee’s recommendation notwithstanding, FDA initiated regulatory action against those N-2 type formulations that were commercially marketed in interstate commerce in obvious violation of the new drug provisions of the Act. In addition, we notified State governments of our actions.
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We have forwarded your letter to the appropriate office within FDA’s Center for Drug Evaluation and Research (CDER) for review and any appropriate follow up and have also forwarded a copy to the Ohio State Dental Board. In closing, we want to assure you that we are extremely sensitive to the gravity of the problem of adverse reactions to any drug, and that this Agency is committed to taking appropriate regulatory action to remove any unapproved new drug from the market place. |
DEPARTMENT OF HEALTH & HUMAN SERVICES