September 11, 1992

Carolyn A. Tylenda, D.M.D., Ph.D. -
Food and Drug Administration

Betty W. Collins -
Food and Drug Administration

W. Don Galloway, Ph.D. -
Food and Drug Administration

Carol M. Lee -
Food and Drug Administration

Charles Somerville
Food and Drug Administration

The Regulatory Work Group has considered its assigned discussion topics and has developed the following recommendations:

Determine whether the absence of definitive risk information for dental amalgams should alter the product's regulatory status as a medical device.

Classification of dental devices was published in December 1987. Dental amalgam was considered to consist of two devices: dental mercury and amalgam alloy. Dental mercury, a class I device, is defined in 21CFR 872.3700 as "a device composed of mercury intended for use as a component of amalgam alloy in the restoration of a dental cavity or a broken tooth." Class I devices are those for which "General Controls" are sufficient to assure safety and effectiveness. General Control requirements include registration of each manufacturing location, listing of the device(s), possession of a cleared Premarket Notification [510(k)], and Good Manufacturing Practices (GMPs). General Controls are minimal requirements that apply to class I, II and III devices. Amalgam alloy, a class II device, is defined in 21CFR 872.3050 as "a device that consists of a metallic substance intended to be mixed with mercury to form filling material for treatment of dental caries." A class II device is one for which reasonable assurance of safety and effectiveness can be achieved through the application of "Special Controls". Special Controls include postmarket surveillance, performance standards, patient registries, development and dissemination of guidelines, recommendations and other appropriate actions. A class III device is one for which insufficient information exists to assure that general and special controls provide reasonable assurance of safety and effectiveness. Generally, class III devices are those that sustain or support life, are of substantial importance in preventing impairment of human health or present potential unreasonable risk of illness or injury.

In recent months, data purported to establish risks associated with dental amalgam have undergone extensive scrutiny by several panels of experts. In March 1991, FDA held a meeting of the Dental Products Panel to assess the scientific evidence regarding the toxicity of dental amalgam. The Dental Products Panel consists of experts selected from across the country to help FDA evaluate the safety and effectiveness of devices and to make recommendations to FDA on device related issues. The Panel unanimously agreed that sufficient valid scientific data do not presently exist that establish dental amalgam to be a health hazard in humans. However, the Panel agreed that the information presented at the panel meeting raises questions that warrant further research. In November, 1991 the CCEHRP Subcommittee on Risk Assessment completed its report on the evaluation of risk from exposure to mercury vapor from dental amalgam, and reached a similar conclusion. While it is clear that mercury vapor is continually released from dental amalgam, it is not clear that this exposure leads to toxicity. However, the potential for toxic effects due to low levels of exposure to mercury vapor from dental amalgam restorations must not be disregarded. The FDA Dental Products Panel, the CCEHRP Risk Assessment Subcommittee, and the CCEHRP Benefits Subcommittee on Amalgam, as well, have proposed that well designed scientific studies be conducted to precisely define those potential toxic effects, if any.

The Regulatory Work Group recommends that the Food and Drug Administration view dental amalgam as a kit, in that both mercury and alloy must be used together to create dental amalgam restorative material. FDA considers the class of the kit to be that of the component of the kit assigned the highest classification. In this case the kit would be viewed as a Class II device because that is the classification of amalgam alloy. No reclassification action would be required. Because the great majority of dentists use pre-encapsulated amalgam, this consolidation would simplify and clarify FDA's handling of dental amalgam submissions.

The Regulatory Work Group feels that reclassification of dental amalgam to Class III should not be readdressed until a body of substantial scientific evidence establishes that dental amalgam restorations are a health hazard. The Research Work Group is charged with developing a list of research objectives and priorities for determining the toxicity and toxic potential of mercury vapor released by dental amalgam. In view of this activity, the Regulatory Work Group believes it is prudent to delay consideration of reclassification of dental amalgam to class III for a reasonable period of time to allow these studies to be carried out. From a practical viewpoint, it would be difficult for amalgam manufacturers to carry out the studies required for premarket approval applications that would unequivocally establish the safety of dental amalgam restorations. The variety of approach and complexity in design required to produce meaningful data would require the cooperation of the public health and scientific communities. If it becomes clear that research directed toward addressing public concerns on the safety of dental amalgam restorations will not be forthcoming, FDA could then reconsider the question of reclassification.

From a benefit versus risk standpoint, the benefit of dental amalgam restorations is clear while the risk has not been established. The Regulatory Work Group is concerned that reclassification to class III at the present time would send a strong message to the public that dental amalgam restorations are dangerous. Without definitive risk information for amalgam and other restorative materials, and as other dental restorative materials are class II devices, it is consistent for dental amalgam to be treated as a class II device.

As described in 21CFR 807.87(e), Premarket Notification [510(k)] submissions must include "proposed labels, labeling, and advertisements sufficient to describe the device, its intended use, and the directions for its use". In regard to dental amalgam, instructions would inform the user, the dentist, on proper and safe handling of the device to insure the safety of the dentist and dental personnel as well as the patient.

The status of labeling materials for dental amalgam was discussed in a joint meeting between the CDRH Dental Amalgam Task Force and the Regulatory Work Group. A review of labeling material for dental amalgams is underway to establish if current labeling meets current FDA regulatory labeling requirements.

There are other restorative materials which can be substituted for dental amalgam in certain cases. These have been identified and discussed in the CCEHRP Benefits Subcommittee report. The field of restorative dentistry is an ever growing one with new products being developed and marketed daily. The diversity of restorative materials available to the dentist today is vast in comparison to that of a decade ago. Along with this tremendous technological improvement in handling properties that result in better functional qualities, increased longevity of the restoration and improved ease of handling is an increase in the number of potentially toxic materials that are in continuous contact with the oral mucosa. While much attention has been devoted to the potential toxicity of dental amalgam, less has been paid to the vast array of other restorative materials.

On the whole, use of dental restorative materials has not generated significant numbers of reports of adverse reactions. On the contrary, the incidence of side effects from restorative materials is reported to be very low. The most commonly reported problem with these materials is that of sensitivity reaction.

The Regulatory Work Group recommends that, based on currently available information, a statement be placed in the labeling accompanying amalgam and all other restorative materials

1. Advising the clinician of possible sensitivity reactions to the material, and
2. If a sensitivity reaction occurs, instructing him/her to discontinue use of that product and to substitute a suitable alternative restorative material.

While definitive information regarding the potential toxic side effects of all dental restorative materials is not yet available, the Regulatory Work Group feels that clinicians should be advised to use barrier techniques as much as possible to reduce inhalation and ingestion of restorative materials that are being placed or being removed. Possible mechanisms for accomplishing this include a statement in the labeling of the restorative material, and education of the clinician through other means. We suggest that the Education Work Group explore this issue.

The Regulatory Work Group further recommends that a comprehensive list of ingredients contained in the labeling of amalgam and other restorative materials be placed on the outside of the package containing the restorative material. By doing so, the clinician would be made aware of the materials he/she is placing in a patient's mouth, and would be better able to make an appropriate selection, and to identify a substitute, when necessary. The clinician would also be able to pass on this information to any interested and concerned patients.

The ingredients should be listed in order of decreasing percent composition (by weight), and include all coloring and flavoring agents. That is, the ingredient present in greatest amount would be listed first. Also, instructions for safe handling and disposal as well shelf life and information on optimal storage conditions should be provided.

It is difficult to assess the significance of the current data base (Device Experience Network) on adverse reactions to amalgam. Publicity on an issue plays a pivotal role in generating reports of incidents. The recent wave of media attention and the resulting public concern to the potential harmful effects of amalgam have resulted, in a short time span, in an accumulation of adverse reaction reports. It is difficult to determine a trend among the numerous ailments that have been attributed to the presence of dental amalgam. Moreover, subtle, and especially delayed, adverse reactions to any material are likely to be under-reported, whereas highly publicized purported effects may be over-reported. A summary of all data collected should be made available to government and private researchers to help them identify key areas for development of clinical studies.

The data collected to date through the Device Experience Network was reviewed in a joint meeting of the Regulatory Work Group and the CDRH dental amalgam task force. It was decided that a letter will be sent to each individual who submitted a report asking that person to allow his/her physician and dentist to release information in his/her medical and dental history. Information such as medication use, family history of illness, allergies, number of dental restorations, types of dental restorative material used, and length of tune restorations were present might be helpful in detecting a commonality among this group of individuals. Documented medical findings before and after dental amalgam removal would be especially useful.

The Regulatory Work Group believes that the dental community as a whole is not familiar with existing mechanisms for reporting adverse effects from dental devices. In order to encourage the reporting of adverse reactions to dental restorative materials, the Regulatory Work Group recommends that a program be developed aimed at publicizing the Medical Device & Laboratory Product Problem Reporting Program (PPRP). We recommend that the Education Work Group develop a plan for educating the dentist, and perhaps the patient as well, about the existence of the program and the importance of reporting an adverse device reaction. It cannot be emphasized enough that it is crucial for FDA to be aware of adverse incidents involving devices in order to develop a meaningful response.

In addition to publicizing the existence of the PPRP, the format of the form and the mechanism by which device reporting forms are distributed deserve review. The form should be user-friendly, i.e., with easy to follow instructions for completion and for return to FDA. The mechanism of distribution is important in capturing the attention of the dentist and the office staff so that when the material arrives at the office, it will not be lost among the myriad of bills, magazines, advertising material, and bulk mail.

The Regulatory Work Group is not aware of unethical practices by manufacturers regarding bogus claims of toxicity from dental amalgam, and the promotion of amalgam removal and replacement by other materials. In a discussion with the American Dental Association (ADA), the ADA representative agreed with this view. Some manufacturers have promoted their products as alternatives to dental amalgam, which they are.

There are reports that some individual dentists are promoting this practice to patients in their individual offices. The present assessment of the ADA is that it is difficult to determine the extent of this activity. Information dissemination on "mercury-free" dental practices, which advocate removal of dental amalgams and replacement with alternative restorative materials, may be through newsletters published by one of several antiamalgam organizations, or by word-of-mouth.

Advertising is considered to be labeling. If individual dentists were participating in false advertising such as claiming that dental amalgams are toxic to humans or causative agents for diseases, and if literature purporting these claims were on the premises of the dentist's office, FDA would have the authority to take legal action against that dentist. However, this situation is unusual in comparison to the more common case of illegal use of a device. In view of this, the Regulatory Work Group feels that it would be more appropriate for this issue to be handled by State licensing and regulating bodies, or by the state professional association, i.e., State dental association. If there does not appear to be a problem, or if the problem is a minor one, States may elect to issue voluntary guidelines. If, however, the problem becomes blatant, and could adversely affect the dental profession as a whole, the State may wish to develop mandatory regulations.

In summary, the Regulatory Work Group makes the following recommendations:

1. That FDA consider dental amalgam to be a single class II device. This would be accomplished without any reclassification activity, but by regarding dental amalgam as a "kit."
2. That labeling materials include statements about the safe handling and use of dental amalgam, as well as information on the clean-up of spills and proper handling, storage, and disposal of waste amalgam.