Navigating FDA Compliance (Regulatory Standards CE)

Unregulated medical devices were once widely available to the public and often caused serious health hazards or even death. Ultimately, the public demanded protection against the possible harm caused by medical devices. In response, the US government created an agency responsible for the protection of public health known as the Food and Drug Administration (FDA) in 1906. Since its inception, the FDA has continued to tighten its policies to increase the safety of medical devices.

Still, in many cases little is known about the origin and composition, indications and contraindications, manufacturing processes, and effects that countless medical devices have on human health. Even 100 years into the FDA’s existence, dental laboratories were relatively unregulated.

However, in recent years dental laboratories have been subjected to increased scrutiny as regulatory bodies have learned about the possible dangers associated with dental prostheses and turned their attention to the manufacturing and sales of these devices. As this scrutiny becomes more intense and widespread, many laboratory owners and managers still are not fully aware of the regulations that apply to their industry.

FDA

The FDA is the oldest regulatory consumer protection agency in the federal government. It is overseen by the Department of Health and Human Services. Oversight of dental laboratory technology falls within the FDA’s Center for Devices and Radiological Health (CDRH), within the Office of Medical Products and Tobacco.¹ The FDA works on a case-by-case basis; understanding how it conducts its diverse operations is often confusing and difficult.

The FDA’s mission is simply to be responsible for public health. This enormous undertaking is handled in various ways, including regulating products that are new to the market; regulating manufacturers, marketing, and distribution; ensuring the security of food supply; and promoting the development of products.

The FDA has regulatory authority over a very wide spectrum of items produced domestically and internationally that can affect the health of US citizens, including dental prostheses. The agency fulfills its mission through the review and pre-market clearance of new products (preclinical and clinical studies, manufacturer information about the product); monitoring (review, investigation, post-clearance, and surveillance of new risks); enforcement/compliance; and research. The FDA’s basic working principles are built on science-based decision-making; leveraging the scarce resources available via collaboration among government, academia, and industry; enforcement; and transparency. As of 2012, the FDA had 14,648 full-time employees, including 1,413 who were employed by the CDRH.²

Medical Device Regulations: Historical Perspective

The early regulations of medical devices date back to the Federal Food, Drug and Cosmetic Act of 1938 (FD&C Act). This was the first US law to address restrictions placed on medical devices. It enacted a review for new premarket drugs and banned interstate shipment of misbranded, adulterated devices.³

In the 1970s, a number of serious injuries and deaths surfaced in relation to medical implants and other devices on the market. One well-documented example was an intrauterine device designed to prevent pregnancy that had a design flaw that caused serious injuries. When 300,000 lawsuits followed, the manufacturer voluntarily took the device off the market.³

Device-specific provisions were added to the FD&C Act on May 28, 1976. The 1976 Medical Device Amendments defined the term device (201(h) of the FD&C Act), added premarket clearance of devices, increased FDA enforcement authority, and authorized the use of outside experts on advisory panels to assist in the regulatory process. The amendments classified devices from Class I to Class III based on their risks. All classes of devices became subject to general controls such as registration (manufacturers must register facilities with the FDA), listing of manufactured products, quality systems (based on good manufacturing practices), correct labeling, and reporting adverse events through the Medical Device Reporting (MDR) system.³

The Safe Medical Devices Act of 1990 broadened device regulations, required user facilities to report device-related deaths and injuries to the FDA and/or manufacturer, and introduced the substantial equivalence for 510(k), special controls, and Humanitarian Device Exemption. Next was the FDA Modernization Act of 1997, which brought the least burdensome route to FDA clearance, added evaluation of automatic Class III designation, and allowed for accreditation of third parties for review of premarket notification (section 510(k)). Then, the Medical Device User Fee and Modernization Act of 2002 introduced user fees, third-party inspections of manufacturing facilities, and new requirements for reprocessed single-use devices. In July 2012, the FDA Safety and Innovation Act modified the reclassification process and simplified it by allowing reclassification to take place through administrative order instead of regulation.³

Besides the aforementioned statutes, regulations written by agencies can become laws. Such is the case of FDA Device Regulations, Title 21 CFR Parts 800. CFR refers to the Code of Federal Regulations. The examples of Title 21 CFR Parts 800 for the Device Regulations are 801: Labeling, 803: Medical device reporting, 814: Premarket approval of medical devices, etc. The numbers skip between regulations so new information can be added if necessary.^3,4 Dental devices are listed under regulation Title 21 CFR Part 872.

Medical Device Definition, Classification, and Controls

Since the dental laboratory profession is inherently tied to FDA-defined medical devices, understanding the basis for FDA regulations is important. According to section 201(h) of the FD&C Act, a medical device is “an instrument, apparatus, implement, machine, contrivance, implant, in vitro reagent, or other similar related article, including any component, part, or accessory” that meets one of the following criteria:

• Recognized in the official National Formulary, or the U.S. Pharmacopoeia, or any supplement to them
• Intended for use in diagnosis of disease or other condition, or in the cure, mitigation, treatment, or prevention of disease
• Intended to affect the structure or any function of the body, and does not achieve its primary intended purposes through chemical action within or on the body and is not dependent upon being metabolized for the achievement of its primary intended purposes.^3,5

The FDA classifies medical devices by evaluating the safety and effectiveness of the device and by weighing any probable health benefit against any probable risk of injury or illness from the use of the device (section 513 (a)(2) of the FD&C Act). The FDA has classified approximately 1700 medical devices in 16 medical specialties or device panels.⁶ Device classification is based on intended use, indications for use, and the level of risk to human health. For a detailed summary of each of the classifications along with examples of dental products in each class, go to insidedentaltech.com/886.

Classification of devices is based upon the controls necessary to protect public health. Controls increase from Class I to Class III and are divided between general and special controls.⁷ General controls include registration of manufacturing facilities, listing of device type, labeling requirements, good manufacturing practices (GMP)/quality system regulations, recordkeeping, reporting device failures (via the MDR system), and banned devices. Special controls are device specific and may include device guidelines, performance standards, post-marketing surveillance, patient registries, and other applicable actions necessary to provide adequate assurance of safety and effectiveness. Class I devices are based on general controls and most are exempt from Premarket Notification 510(k).³

When insufficient information exists and general and special controls are not sufficient to assure the safety and effectiveness of the device, the FDA uses more stringent measures such as Premarket Notification 510(k) and Premarket Approval (PMA). Both 510(k) and PMA are more detailed scientific and regulatory reviews that examine the safety and effectiveness of the devices based on their risk to public health. 510(k) is required when the device is first introduced to the market, or when altering the device’s indications for use or modifying the device significantly and affecting its safety or effectiveness, ie, change in design, materials, chemical composition, energy source, or manufacturing process.⁸ Most Class II devices require 510(k) and Class III devices require PMA. 510(k) requires substantial equivalence to a comparable existing device (predicate device) on the market and must be cleared by the FDA prior to marketing. 510(k) is required for Class II devices and in some instances for Class III or even Class I devices. PMA is required for Class III devices to begin marketing, and the application must demonstrate the safety and effectiveness of the device through valid scientific research supported by clinical data; the FDA must approve it prior to marketing. PMA is the most rigorous and lengthy FDA application process.⁸ The FDA examines approximately 3000-4000 510(k) and 30-50 PMA applications per year.³

Hence, if a business wants to introduce a device to the US market, and a similar device already exists on the US market, the business can submit 510(k) validating that its device is substantially equivalent to a predicate device. A predicate device is legally marketed in the US and is not subject to PMA (not a Class III device). Further, a predicate device can be either a pre-amendments device (legally marketed in the US before May 28, 1976) that does not require PMA or an existing device that is substantially equivalent through the 510(k) process, and one that is considered a Class I or Class II device. Substantial equivalence of a device can be demonstrated through the similarity to the predicate device in the intended use, design, energy used or delivered, materials, chemical composition, manufacturing process, performance, safety, effectiveness, labeling, biocompatibility, standards, and other means.

Substantial equivalence relates to the devices legally marketed in U.S. prior to May 28, 1976, or a device that was reclassified from Class III to Class II or I, or a device that was found to be substantially equivalent through the 510(k) premarket notification process. However, if the device is found not substantially equivalent (NSE), the business can resubmit a new Premarket Notification 510(k) with new data, request Class I or II designation through the De Novo process for newly introduced devices where no predicate devices exist, or submit a PMA Application for a Class III device.³ Dental devices fabricated by laboratories are either not classified by the FDA or fall into Class I or II and are often exempt from 510(k).¹⁰

An example of an FDA pre-amendments predicate device legally marketed before May 28, 1976, is Valplast® Flexible Partial material, introduced in the 1940s by Arpad F. Nagy, CDT. Valplast is registered with the FDA as a manufacturer, and its Flexible Partial material is classified as a Class II medical device. Nagy’s grandson Justin Marks, CDT, owner of Master-Touch Dental Laboratory, says even though most Class II devices are required to have Premarket Notification, by being grandfathered in, Valplast Flexible Partial material did not have to go through the 510(k) process and now serves as a predicate device for the industry.

FDA Relationship With the Dental Laboratory Industry

Data from the Bureau of Labor Statistics through the second quarter of 2015 indicated the existence of 6,584 dental laboratories, including 735 single-person laboratories. The former is a 2.7% decrease from 2014, but the data also indicated that laboratories had 44,569 employees, a 0.8% increase from the previous year. Bennett Napier, CAE, Chief Staff Executive for the National Association of Dental Laboratories (NADL), states that it would be very difficult to track how many laboratories are registered with FDA as the agency does not track establishments by industry classification. FDA public records, however, indicate that more than 25 domestic and 30 foreign dental laboratories had been inspected in the 24 months prior to March 2016, an increase from previous years.

Dental laboratories fabricate dental prostheses that may fall into one of the categories of FDA medical devices. Based on FDA classification, the laboratory may have to register or file documentation with the FDA to seek approval for in-house fabrication; its other options are to use equipment cleared by the FDA to fabricate such devices, or to direct the milling and printing to centers that have FDA clearance. Napier says, “A laboratory could mill custom abutments in-house if it registers as a Contract Manufacturer for some systems.” With CAD/CAM systems that received 510(k) clearance, the laboratory itself does not need to register to mill in-house FDA medical devices while using FDA-cleared equipment. The manufacturer may seek FDA clearance for its devices by demonstrating that FDA regulatory standards and parameters are followed. For custom implant abutments, proper angulation parameters must be installed in the equipment and followed by the laboratory without the possibility of modification outside of the FDA-allowed scope. Similarly, milling and printing centers can obtain clearance from the FDA as long as FDA regulations and parameters are followed in the production of FDA-cleared medical devices.

FDA clearance is required for anyone using CAD/CAM to fabricate custom implant abutments. However, the CAD/CAM systems used to fabricate other dental prostheses such as crowns, bridges, partial dentures, and full dentures do not currently require FDA clearance. In fact, according to the NADL, the only dental laboratories that need to register with the FDA are those involved in the sale of sleep apnea devices, CAD/CAM fabrication of custom abutments, importation of restorations such as crowns, bridges, dentures, and custom abutments, or repackaging/resale of ceramic or other materials. Laboratories not involved in such activities are exempt from registration with the FDA altogether.¹¹

All dental laboratories fall under the jurisdiction of the FDA, and the agency’s regulations cannot be ignored. The FDA can conduct an audit of any dental laboratory in the US. According to the NADL, through registration the FDA identifies device manufacturers and their products, and prioritizes inspections based on higher-risk devices/situations. Higher priority is given to Class III devices, implantable devices, life-supporting and life-sustaining devices, new devices to the market, or devices/situations involved with significant violations in the past.¹² The simplest way for the FDA to find unregistered laboratories and manufacturers of medical devices is by reviewing their websites and marketing materials, receiving patients’ complaints, or inspecting new shipments into the country.

If a violation is detected, the FDA can use its regulatory enforcement powers in a variety of ways. First, the FDA seeks a corrective action plan with a timetable to respond or fix the problems. Then it tries to levy financial penalties, followed by halting production and preventing any further product from leaving the facility. If that does not remedy the violation, the FDA seeks an injunction to shut the business down, followed by criminal penalties. Fines are based on the circumstances and seriousness of the violations. Most violations are resolved with a correction plan. The FDA turns most often to that first step to allow the facility to fix the problem in a timely manner.¹¹

To remedy future noncompliance with various regulatory authorities, it is important for dental laboratories and manufacturers to embrace regulatory and industry standards and stay informed about new developments.

FDA Registration and Medical Device Taxes

FDA registration includes a fee, which increases annually. The fee is the same regardless of the size of the business or group registering. According to the FDA, the electronic registration process, a collection of information on form FDA 3673, should take no longer than 30 minutes per response for firms annually registering their establishments and approximately 15 minutes for annually listing the devices.¹³

Domestic laboratories that do not sell sleep apnea devices, fabricate CAD/CAM custom abutments, import restorations, or repackage/resell materials are exempt from FDA registration requirements under Title 21 CFR Part 807.65, Exemptions for device establishments: “(i) Persons who dispense devices to the ultimate consumer or whose major responsibility is to render a service necessary to provide the consumer (ie, patient, physician, layman, etc.) with a device or the benefits to be derived from the use of a device; for example, a hearing aid dispenser, optician, clinical laboratory, assembler of diagnostic X-ray systems, and personnel from a hospital, clinic, dental laboratory, orthotic, or prosthetic retail facility, whose primary responsibility to the ultimate consumer is to dispense or provide a service through the use of a previously manufactured device.”

The list of the types of businesses that must register with the FDA can be found under Title 21 CRF Part 807.20, “Who must register and submit a device list?”¹⁴ Foreign manufacturers of devices must also register with the FDA under Title 21 CFR Part 807.41, “Identification of importers and persons who import or offer for import.”

By registering with the FDA, the manufacturer or importer is also responsible for filing Form 720, the Quarterly Federal Excise Tax Return, and required to pay taxes to the Internal Revenue Service on the sale of certain medical devices (section 4191 of the Internal Revenue Code). The 2.3% Medical Device Excise Tax applied to sales of taxable medical devices after 2012. A taxable medical device is a device that is listed with the FDA under section 510(j) of the FD&C Act (21 CFR part 807), unless the device falls within an exemption from the tax, such as the retail exemption. However, a law signed on December 18, 2015, the Consolidated Appropriations Act, 2016 (Pub. L. 114-113), incorporated a two-year suspension on the Medical Device Excise Tax. Consequently, this tax does not apply to the manufacturers, producers, or importers of taxable medical devices, including domestic dental laboratories, during the period from January 1, 2016 to December 31, 2017.^14-15

Medical Device Reporting, FDA

When a device becomes available on the market, the FDA continues to monitor its performance via Medical Device Reporting (21 CFR Part 803). MDR is a fully online system that allows for identification and monitoring of adverse events of medical devices, such as device malfunction, serious injury, or death, which must be reported. The manufacturers, user facilities, and importers of medical devices must submit mandatory reports. User facilities must submit reports to the FDA and to the manufacturers of the device (if known) no later than 10 business days after learning of the event. Importers of medical devices must submit reports to either the manufacturers or the FDA, or both, depending on the report type, no later than 30 calendar days after learning of the event. The manufacturers of medical devices have either 5 or 30 days to report to the FDA, depending on the type of adverse event. Health care professionals, consumers, and patients submit voluntary reports. MDRs are stored in the Manufacturer and User Facility Device Experience database and have been collected since 1991.¹⁶ Currently, the FDA makes data from this database available on its website for download and review¹⁷ as well as for online searching.

Latest on Regulations of Milled Implant Abutments

New FDA developments have emerged recently in relation to CAD/CAM fabrication of custom implant abutments. Due to increased demand for these products, the FDA became more concerned with potential risks associated with patient health. The issue surfaced because FDA design parameters were not always followed when CAD/CAM technologies were being utilized to fabricate custom abutments. In recent months, the FDA intensified its enforcement efforts by sending compliance letters to manufacturers, milling centers, and dental laboratories. According to Eric Thorn, Esq., NADL Chief Staff Executive, “Anyone making the implant/abutment interface is no longer a dental laboratory from a regulatory perspective, but rather a manufacturer of a Class II medical device and must obtain 510(k) clearance.” Further, the FDA requires that the manufacturer’s CAD/CAM instructions must be 510(k) cleared to incorporate hard stops so it is not possible for the laboratory to surpass FDA-cleared design parameters. Without these clearances, “the laboratory can only hand-mill custom abutments from single-piece abutment blanks with a pre-milled connection platform and a large cylinder for fabrication of the collar and post.”¹⁸

Those laboratories that offer CAD/CAM custom-milled abutments and are not utilizing FDA-cleared technologies may be violating FDA regulations and may come under FDA scrutiny. It is possible that in the near future the FDA will create new guidelines related not only to CAD/CAM custom abutments but also to other medical devices fabricated with digital means in dental laboratories.

FDA Compliance

Many dental organizations, including laboratories, are taking a proactive position by looking into ways to resolve some of the pressing regulatory issues. The International Organization for Standardization (ISO) continues to develop and publish International Standards (iso.org). A laboratory can become certified in ISO standards through external certification bodies. As for the US market, the NADL and state associations monitor and work with legislatures to enact favorable laws and provide the industry with timely updates. The NADL also adopted the Dental Appliance Manufacturers Audit System (DAMAS) based on the quality system management principles specified by the ISO and reflecting the FDA’s Quality System/Good Manufacturing Practice (QS/GMP) standards that are required of all US-based dental laboratories regardless of registration requirements. By becoming DAMAS certified (nadl.org/damas), a dental laboratory will be well prepared for FDA compliance. According to Napier, the U.K.’s Dental Laboratories Association Ltd. started using DAMAS in the mid-1990s, and the NADL initiated and modified the North American version in 1999. Currently, there are 32 DAMAS-certified dental laboratories in the US. For third-party auditors or consultants, the laboratories can contact the NADL directly by visiting nadl.org.

Conclusion

Change is not new to the dental laboratory profession, yet complying with evolving regulations is a challenge that all laboratories will need to manage. New regulations touching the dental laboratory profession are a prelude to the tightening that can be expected in upcoming years. According to the NADL, with new and increased funding for the FDA, facility inspections will increase; more emphasis will be placed on product safety during production and through import; the raw material supply chain will undergo higher scrutiny; and workforce proficiencies as well as the standards of the profession will be questioned.

For the future survival of the profession, it is more important today than ever before that laboratory owners and managers keep up with industry standards, stay informed, and understand applicable regulations.

Disclosure

The author had no disclosures to report.

References

1. U.S. Food and Drug Administration. FDA Organization. http://www.fda.gov/AboutFDA/CentersOffices/default.htm. Updated February 25, 2015. Accessed January 28, 2016.

2. U.S. Food and Drug Administration. Food and Drug Administration Distribution of Full-Time Equivalent (FTE) Employment: Program Level. http://www.fda.gov/downloads/AboutFDA/ReportsManualsForms/Reports/BudgetReports/UCM301553.pdf. Accessed January 28, 2016.

3. Pirt, N. FDA 101: An Overview of FDA's Regulatory Review and Research Activities: FDA’s Regulatory Framework: Device Regulation. U.S. Food and Drug Administration. Online Lecture. http://google2.fda.gov/search?q=FDA%20101&client=FDAgov&proxystylesheet=FDAgov&output=xml_no_dtd&site=FDAgov&requiredfields=-archive:Yes&sort=date:D:L:d1&filter=1. Published October 23, 2015. Accessed December 18, 2015.

4. Food and Drug Administration. Code of Federal Regulations (CFR). http://www.fda.gov/medicaldevices/deviceregulationandguidance/overview/ucm134499.htm. Updated December 31, 2014. Accessed January 28, 2016.

5. U.S. Food and Drug Administration. What is a Medical Device?. http://www.fda.gov/AboutFDA/Transparency/Basics/ucm211822.htm. Updated December 28, 2015. Accessed January 28, 2016.

6. Shutton B. Overview of Regulatory Requirements: Medical Devices - Transcript. Food and Drug Administration. http://www.fda.gov/Training/CDRHLearn/ucm281656.htm. Updated October 14, 2014. Accessed January 24, 2016.

7. U.S. Food and Drug Administration. Classify Your Medical Device. http://www.fda.gov/medicaldevices/deviceregulationandguidance/overview/classifyyourdevice/default.htm. Updated July 29, 2014. Accessed January 28, 2016.

8. U.S. Food and Drug Administration. Premarket Approval (PMA) http://www.fda.gov/medicaldevices/deviceregulationandguidance/howtomarketyourdevice/premarketsubmissions/premarketapprovalpma/default.htm. Updated August 19, 2014. Accessed January 29, 2016.

9. U.S. Food and Drug Administration. CFR-Code of Federal Regulations Title 21: Part 872 Dental Devices. http://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfcfr/CFRSearch.cfm?CFRPart=872. Updated April 1, 2015. Accessed January 28, 2016.

10. U.S. Food and Drug Administraion. Medical Device Exemptions 510(k) and GMP Requirements. https://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfpcd/315.cfm?GMPPart=872. Updated February 15, 2016. Accessed February 15, 2016.

11. National Association of Dental Laboratories. NADL Guide to Food and Drug Administration Inspections of Dental Laboratories. http://dentallabs.org/wp-content/uploads/2013/07/NADL-Report-on-Food-Drug-Administration-Activities.pdf 2015.

12. U.S. Food and Drug Administration. What does FDA Regulate?. http://www.fda.gov/AboutFDA/Transparency/Basics/ucm194879.htm. Updated December 28, 2015. Accessed January 28, 2016.

13. U.S. Food and Drug Administration. Device Registration and Listing. http://www.fda.gov/MedicalDevices/DeviceRegulationandGuidance/HowtoMarketYourDevice/RegistrationandListing/. Updated August 3, 2015. Accessed February 6, 2016

14. Internal Revenue Service. Medical Device Excise Tax: Frequently Asked Questions. https://www.irs.gov/uac/Medical-Device-Excise-Tax:-Frequently-Asked-Questions. Updated January 11, 2016. Accessed February 7, 2016.

15. Thorn E J. Medical Device Excise Tax Member Guidebook. National Association for Dental Laboratories. 2013.

16. U.S. Food and Drug Administration. CFR-Code of Federal Regulations Title 21: Part 803 Medical Device Reporting. http://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfcfr/CFRSearch.cfm?fr=807.41. Updated April 1, 2015. Accessed January 28, 2016.

17. U.S. Food and Drug Administration. Manufacturer and User Facility Device Experience Database (MAUDE). http://www.fda.gov/medicaldevices/deviceregulationandguidance/postmarketrequirements/reportingadverseevents/ucm127891.htm. Updated February 3, 2016. Accessed February 21, 2016.

18. Thorn, E. FDA Sharpens Focus on Implant Abutments. Journal of Dental Technology. 2016.

More on Classifications

For a print-ready sheet detailing classifications and examples for each class of medical device, go to insidedentaltech.com/idt886.

This article was double-blind peer reviewed by members of IDT’s Editorial Advisory Board

About the Author

Renata Budny, MBA, MDT, CDT, FNGS
Restorative Dentistry
New York City College of Technology
City University of New York
Brooklyn, NY