373
Vol. 52, No. 6, Special Issue 1992
FDA and ADA Evaluation of Dental Implants David Schumann, DDS
5101 S.Keeler Avenue Chicago, IL 60632 Abstract The FDA classification of endosseous dental implants (€01)is reviewed. Factors impacting the long-term efficacy of dental implants and the guidelines for development of ED1 are enumerated. The role of the ADA in evaluation of EDls is also discussed. Recommendations for development of performance criteria and reporting format are made. Key Words: endosseous dental implants, FDA, ADA, equivalency.
Regulation of the manufacture, sale, and distribution of medical devices by governmental authoritiesis necessary to ensure that minimum patient safety standards are met. The level at which dentistry is practiced varies widely worldwide and the standards in effect for a given market should be established with input fromorganized dentistry in the specific market under consideration. FDA regulations (US marketplace) concern endosseous dental implants (EDIS),which are defined as "devices surgically implanted into the upper and/or lower jaws to provide support for prosthetic appliances such as artificial teeth, and to restore the patient's chewing function." Current guidelines regulate endosseousdental implants, abutments, and prosthetic components. The operative mechanisms involved in "osseointegration" (clinicallydefined as the direct connection of living ordered bone and a load bearing implant)are not understood fully at the ultrastructural level. Osseointegration is a necessary prerequisite to meaningful implant reconstruction of dental deficits. The fusion of the anchorage unit (implant) to host bone is the foundation for the reconstruction. Animal and human preclinical trials are the ultimate means to deduce the safetyand effectiveness of implantable materials, given the lack of knowledge regarding interface physiology. Studies in the literature (1)report long-term follow-upon human subjects.These reports substantiate the specific products and methods used in the treatment of reported patients. Many related issuesmay impact the long-termclinical efficacy of dental implants, including: biocompatibility of the implant's surface, macrostructure of the implant surface (surface topography), microstructure of the implant surface (surface texture), surfacepreparation after machining (cleaning), mechanical properties of the imJ Public Health Dent 1992;52(6):373-4
plant components, method of sterilization, packaging method, and storage conditions. All of these parameters can impact the success rates of the implantable materials and effect their safetyand effectiveness.Each proprietary system of implants and abutments should proceed through the scientific process verifying the implant design and surgical protocol, culminating in human preclinical trials. Extrapolating from the data compiled by others in the clinical research arena may be appropriate to create new scientific models. However, device-specifi preclinical documentation is essential prior to marketing these devices for general use. In 1987 the FDA reclassified endosseous dental implants as class I11 medical devices, which would make them subject to the premarket approval guidelines. In 1988 the "Guidance for Arrangement and Content of a Premarket Approval (PMA) Application for EDIs" was developed and published. In 1989 the FDA proposed a rule that would require a PMA based on the provisions of the 1988 "Guidance." The PMA requirements are much more stringent than those of the Premarket Notification, 510(k).They require a more detailed investigation by the manufacturer in many respects. PMA guidelines are very appropriate in light of the lack of knowledge of operative mechanisms at the level of the bioactive interface, and the variety of products, packaging methods, and delivery systems presently available. Of particular importancein assessingeffectivenessare human preclinical trials, which ultimately verify the safety and effectiveness of a given product system. It is in these phases of development (animal and human studies) that protocols and designs receive final validation. Currently EDIs are classified as class I11 medical devices requiring 510(k)notification, the premarket reporting format of class I1 devices. A 510(k)notificationallows demonstration of "substantial equivalency" to implants that have been marketed prior to the enactment of the Medical Device Amendments (May 28, 1976). Equivalency is assessed on the basis of mechanical drawings of the product and stated applications for the products, including indications and contraindications. The result of the "substantial equivalence" regulatory position hasbeen that little research or clinical documentation has occurred prior to bringing an implant product to market, other than to demonstrate a similarity to a product already approved. Biocompatibility tests, mechanical tests, animal studies, or human preclinical trials
Journalof Public Health Dentistry
374
have been required only if substantial equivalency was challenged by the FDA reviewer. If substantial equivalence is challenged by the FDA, any of the above validation tests could be requested to verify safety and effectiveness of the product in question. A situation of uncertainty has been created for manufacturers when preparing for market release of new products. Are the new products essentially equivalent or not? With the acceptance of the proposed rule requiring reclassification of all EDIs as class 111 medical devices requiring PMAs, the following requirements must be met: Animal (nonclinical laboratory) studies with six study criteria specified Clinical investigations involving human subjects with 11criteria specified Mechanical drawings of all products Mechanical tests: hardness, compressive strength, bending strength, tensile strength, yield strength,modulus of elasticity and fatigue analysis Surface quality validation, poststerilization Claims relative to special surface preparation or characteristics affecting bone bond, gingival attachment, or load distribution must be detailed. Manufacturing controls, inluding: --Quality control standards set for final production. -Filing complete manufacturing process documentation. -Maintaining traceability of manufacture of products. -Sterilization method must be specified. Performance standards, as yet, have not been set. The Harvard ConsensusConference (1980)or the criteria proposed by Albrektsson and Zarb (2) could serve as a basis for performance standards. System reliability analysis, both predictive and retrospective assessing -potential for patient injury -potential for required corrective surgery -potential for soft and/or hard tissue loss related to product use Provisions for postmarket surveillance(track products to individual clinicians who purchased them). These areas of regulatory scrutiny are manifested in the following practical applications. Good Manufacturing Practices (GMPs) specify the daily production of approvedproductsaccordingto specificprocedures. Fulfillment of minimum performance standards, both me-
.
chanical and clinical, could be used to validate claims of implant success. Class 111status requiring PMAs would be in the best interest of patientsbeing treated with EDIs. The additional expense incurred by manufacturers is reasonable in light of the potential harm to the public from unproven products. Additionally regulatory requirements would lead to continued scientific investigation with concomitant product improvement due to increased knowledge at the basic-science level. Minimum performance standards would be only a starting point for improved product performance. The American Dental Association did not make recommendationsregarding dental implantsuntil 1987.At that time two ADA categories were created for classification of dental implants, those fully and provisionally acceptable. Full acceptance required five-year results of treatment in humans to be reported. No specification was made as to the format or reporting criteria of the study. Provisional acceptance can be attained by submission of three years of data reporting treatment in humans. For both classifications no specifics are detailed regarding study format or reporting requirements. The level of scientific scrutiny required for ADA approval has been left to the manufacturer and has resulted in uncertainty as to the value of the ADA seal. These approved classifications have provided little guidance to manufacturers outside the regulation of the FDA. However, the seal of acceptance of the ADA has been widely used in marketing dental implants to add legitimacy to products. The guidance of the FDA has been and will continue to be a valuable source of direction for dental implant manufacturers. The ADA might be most helpful to its membership by creating a unified set of performancecriteria and a specified reportingformat, which dental implant manufacturers must comply with to be awarded the ADA seal. A liaisonbetween the FDA and ADA could create specificguidelines for manufacturers with respect to research, product development, and marketing, with the needs of both the general public and the dental clinicians in mind. References 1. A d d R, Lekholm U, Rodder 8, Branemark PI. A 15-year study of osseointegrated implants in the treatment of the edentulousjaw. Int J Oral Surg 1981;10387-416 2. AIbrektssonT,Zarb G, WorthingtonP, Eriksson AR. The long-term efficacy of currentlyused dental implants:a review and proposed criteria of success. hit J Oral Madofac Implants 1986;l:ll-25.
Vol. 52, No. 6, Special Issue 1992
FDA and ADA Evaluation of Dental Implants David Schumann, DDS
5101 S.Keeler Avenue Chicago, IL 60632 Abstract The FDA classification of endosseous dental implants (€01)is reviewed. Factors impacting the long-term efficacy of dental implants and the guidelines for development of ED1 are enumerated. The role of the ADA in evaluation of EDls is also discussed. Recommendations for development of performance criteria and reporting format are made. Key Words: endosseous dental implants, FDA, ADA, equivalency.
Regulation of the manufacture, sale, and distribution of medical devices by governmental authoritiesis necessary to ensure that minimum patient safety standards are met. The level at which dentistry is practiced varies widely worldwide and the standards in effect for a given market should be established with input fromorganized dentistry in the specific market under consideration. FDA regulations (US marketplace) concern endosseous dental implants (EDIS),which are defined as "devices surgically implanted into the upper and/or lower jaws to provide support for prosthetic appliances such as artificial teeth, and to restore the patient's chewing function." Current guidelines regulate endosseousdental implants, abutments, and prosthetic components. The operative mechanisms involved in "osseointegration" (clinicallydefined as the direct connection of living ordered bone and a load bearing implant)are not understood fully at the ultrastructural level. Osseointegration is a necessary prerequisite to meaningful implant reconstruction of dental deficits. The fusion of the anchorage unit (implant) to host bone is the foundation for the reconstruction. Animal and human preclinical trials are the ultimate means to deduce the safetyand effectiveness of implantable materials, given the lack of knowledge regarding interface physiology. Studies in the literature (1)report long-term follow-upon human subjects.These reports substantiate the specific products and methods used in the treatment of reported patients. Many related issuesmay impact the long-termclinical efficacy of dental implants, including: biocompatibility of the implant's surface, macrostructure of the implant surface (surface topography), microstructure of the implant surface (surface texture), surfacepreparation after machining (cleaning), mechanical properties of the imJ Public Health Dent 1992;52(6):373-4
plant components, method of sterilization, packaging method, and storage conditions. All of these parameters can impact the success rates of the implantable materials and effect their safetyand effectiveness.Each proprietary system of implants and abutments should proceed through the scientific process verifying the implant design and surgical protocol, culminating in human preclinical trials. Extrapolating from the data compiled by others in the clinical research arena may be appropriate to create new scientific models. However, device-specifi preclinical documentation is essential prior to marketing these devices for general use. In 1987 the FDA reclassified endosseous dental implants as class I11 medical devices, which would make them subject to the premarket approval guidelines. In 1988 the "Guidance for Arrangement and Content of a Premarket Approval (PMA) Application for EDIs" was developed and published. In 1989 the FDA proposed a rule that would require a PMA based on the provisions of the 1988 "Guidance." The PMA requirements are much more stringent than those of the Premarket Notification, 510(k).They require a more detailed investigation by the manufacturer in many respects. PMA guidelines are very appropriate in light of the lack of knowledge of operative mechanisms at the level of the bioactive interface, and the variety of products, packaging methods, and delivery systems presently available. Of particular importancein assessingeffectivenessare human preclinical trials, which ultimately verify the safety and effectiveness of a given product system. It is in these phases of development (animal and human studies) that protocols and designs receive final validation. Currently EDIs are classified as class I11 medical devices requiring 510(k)notification, the premarket reporting format of class I1 devices. A 510(k)notificationallows demonstration of "substantial equivalency" to implants that have been marketed prior to the enactment of the Medical Device Amendments (May 28, 1976). Equivalency is assessed on the basis of mechanical drawings of the product and stated applications for the products, including indications and contraindications. The result of the "substantial equivalence" regulatory position hasbeen that little research or clinical documentation has occurred prior to bringing an implant product to market, other than to demonstrate a similarity to a product already approved. Biocompatibility tests, mechanical tests, animal studies, or human preclinical trials
Journalof Public Health Dentistry
374
have been required only if substantial equivalency was challenged by the FDA reviewer. If substantial equivalence is challenged by the FDA, any of the above validation tests could be requested to verify safety and effectiveness of the product in question. A situation of uncertainty has been created for manufacturers when preparing for market release of new products. Are the new products essentially equivalent or not? With the acceptance of the proposed rule requiring reclassification of all EDIs as class 111 medical devices requiring PMAs, the following requirements must be met: Animal (nonclinical laboratory) studies with six study criteria specified Clinical investigations involving human subjects with 11criteria specified Mechanical drawings of all products Mechanical tests: hardness, compressive strength, bending strength, tensile strength, yield strength,modulus of elasticity and fatigue analysis Surface quality validation, poststerilization Claims relative to special surface preparation or characteristics affecting bone bond, gingival attachment, or load distribution must be detailed. Manufacturing controls, inluding: --Quality control standards set for final production. -Filing complete manufacturing process documentation. -Maintaining traceability of manufacture of products. -Sterilization method must be specified. Performance standards, as yet, have not been set. The Harvard ConsensusConference (1980)or the criteria proposed by Albrektsson and Zarb (2) could serve as a basis for performance standards. System reliability analysis, both predictive and retrospective assessing -potential for patient injury -potential for required corrective surgery -potential for soft and/or hard tissue loss related to product use Provisions for postmarket surveillance(track products to individual clinicians who purchased them). These areas of regulatory scrutiny are manifested in the following practical applications. Good Manufacturing Practices (GMPs) specify the daily production of approvedproductsaccordingto specificprocedures. Fulfillment of minimum performance standards, both me-
.
chanical and clinical, could be used to validate claims of implant success. Class 111status requiring PMAs would be in the best interest of patientsbeing treated with EDIs. The additional expense incurred by manufacturers is reasonable in light of the potential harm to the public from unproven products. Additionally regulatory requirements would lead to continued scientific investigation with concomitant product improvement due to increased knowledge at the basic-science level. Minimum performance standards would be only a starting point for improved product performance. The American Dental Association did not make recommendationsregarding dental implantsuntil 1987.At that time two ADA categories were created for classification of dental implants, those fully and provisionally acceptable. Full acceptance required five-year results of treatment in humans to be reported. No specification was made as to the format or reporting criteria of the study. Provisional acceptance can be attained by submission of three years of data reporting treatment in humans. For both classifications no specifics are detailed regarding study format or reporting requirements. The level of scientific scrutiny required for ADA approval has been left to the manufacturer and has resulted in uncertainty as to the value of the ADA seal. These approved classifications have provided little guidance to manufacturers outside the regulation of the FDA. However, the seal of acceptance of the ADA has been widely used in marketing dental implants to add legitimacy to products. The guidance of the FDA has been and will continue to be a valuable source of direction for dental implant manufacturers. The ADA might be most helpful to its membership by creating a unified set of performancecriteria and a specified reportingformat, which dental implant manufacturers must comply with to be awarded the ADA seal. A liaisonbetween the FDA and ADA could create specificguidelines for manufacturers with respect to research, product development, and marketing, with the needs of both the general public and the dental clinicians in mind. References 1. A d d R, Lekholm U, Rodder 8, Branemark PI. A 15-year study of osseointegrated implants in the treatment of the edentulousjaw. Int J Oral Surg 1981;10387-416 2. AIbrektssonT,Zarb G, WorthingtonP, Eriksson AR. The long-term efficacy of currentlyused dental implants:a review and proposed criteria of success. hit J Oral Madofac Implants 1986;l:ll-25.
