Under the Microscope

510(K) is a pre-market submission made to the FDA to demonstrate that the device to be marketed is at least as safe and effective as—that is, substantially equivalent to—a legally marketed device (21 CFR 807.92(a)(3)) that is not subject to pre-market approval.

“A 510(K) clearance is granted when the FDA reviews the 510(K) submission and is satisfied that the proposed device is at least as safe and effective (substantially equivalent) to other legally marketed devices. Once a 510(K) clearance is granted, the medical device manufacturer (or their contract manufacturer) can legally market and sell said device. If there are problems with materials, medical device designs, etc, the traceability that is inherent in a compliant QMS provides for tracking of trends, identification of potential flaws, and ultimately the ability to notify if a recall is ever required for the medical device.”

- Chris Brown, BSEE

Although the majority of dental laboratories have been exempt from registering with the FDA and are mostly immune to inspection, FDA GMPs and QMS regulations have been in place for the past two decades. Now there may be changes to how those regulations are applied.

“FDA regulations and standards under which a laboratory fabricates product have not changed,” says Chris Brown, BSEE, FDA compliance expert and manager at Aclivi LLC, a CAD/CAM equipment consulting company. “It is the method used to manufacture the end product that has changed and how the existing FDA regulations now apply to those dental laboratory processes.”

In the past, most FDA attention focused on laboratories that were registered with the FDA as importers of end products from overseas, manufacturers of Class II devices such as sleep apnea appliances or snore guards, or repackagers/relabelers of Class II devices. The advent of new technologies and digital processes, however, has invited closer FDA scrutiny. The increased volume of restorations coming through offshore channels combined with those produced by new onshore CAD/CAM production centers and automated in-house laboratory processes have eroded control over who or what is creating the end restoration. The responsibility for patient safety has shifted liability from the primary source, the dentist, and onto most of those involved in the supply chain.

“Dental laboratories, whether they wanted to or not, have evolved from a cottage industry to manufacturers of product,” says Tim Torbenson, founder and president of EVO820, a company that offers quality management and compliance services to small to medium laboratories, located in Rancho Mission Viejo, CA. “And it’s to the manufacturers of product that the FDA pays attention.” The potential for large quantities of CAD-designed or CAM-milled restorations produced by machines that perhaps were not properly calibrated, operated, or maintained is what has caught the eye of regulatory agencies. Although most laboratories have put some form of QMS and GMPs in place for day-to-day operations—like remakes, equipment maintenance, employee job descriptions, and training—it’s documenting each of these routines that is often missing.

“If you can’t prove it, then you are not in compliance,” says Bob Savage, vice president of Drake Precision Dental Laboratories. The FDA targeted Drake in March 2017. It was Drake’s first FDA audit in the 10 years that the company had been registered for its worldwide product line and as a contract manufacturer of sleep apnea devices. As a DAMAS laboratory, Drake maintains its QMS through Safelink Consultings’ online digital cloud-based application. Savage had all the requested documentation detailing work instructions for each step in the production process for each product they make and could pull training records proving the competency of the employees carrying out those steps. “The inspector examined the entire process from material lot numbers associated with the device manufacturer, calibration requirements for equipment versus internal records, and QC functions, to packaging and remakes,” says Savage.

While many dental laboratories struggle to understand the applications of FDA rules and guidelines to internal digital processes, the FDA is struggling to understand the operations of a manufacturing community producing tens of thousands of different custom products each day. Customized manufacturing on such a large scale is as foreign to the FDA as understanding the nuances of FDA regulations is to the laboratory industry. NADL strives to help the industry understand compliance issues and to uncover what issues trigger FDA audits as well as areas of laboratory operations that result in special FDA scrutiny. “We’ve definitely seen an uptick in FDA oversight activity,” says Eric Thorn, Esq, chief staff executive at NADL. “One of the NADL’s major initiatives is to help laboratories with compliance and how to prepare for an FDA audit.” However, the NADL was asked recently by the FDA to help their personnel understand the manufacturing processes used in the laboratory. In late June 2017, the FDA invited the NADL—represented by Thorn and current NADL President Jerry Ulaszek, CDT, TE—to meet with FDA officials and 510(K) approval personnel. Ulaszek walked them through typical production processes used in the laboratory.

Whether the laboratory is registered with the FDA as a contract manufacturer of a Class II device, registered as a 510(K)-approved manufacturer, or using an FDA-cleared CAD/CAM system, the FDA is paying close attention. Even laboratory owners who order their custom abutments from 510(K)-approved production centers have felt the sting.

“We just had a laboratory call us last week about a phone conversation he had with the FDA concerning the custom implant abutments he was listing on his website,” says Thorn. “The FDA representative asked for 510(K) numbers on the abutments they were producing. The issue was resolved when the laboratory owner indicated Argen was the manufacturing arm for their custom implant abutments. However, the wording used on the laboratory’s website made it appear as if the laboratory was milling them in-house, and that triggered the oversight.”

For Greg Harris, general manager at Core3D Systems, it was advertising in industry journals that drew attention to the custom implant abutments his company was producing. When he joined Core3D 2 years ago, the production center had a relationship with BioHorizons as an authorized milling center for their custom implant abutments.

“We were using million-dollar machines to mill the 510(K)-cleared abutment blanks in a consistent fashion and in accordance to manufacturer specifications,” says Harris. “However, what I discovered was that just because our facility was milling 510(K)-cleared implant abutment milling blanks, that didn’t mean we were making them in an FDA-compliant fashion.”

In addition to implementing a QMS to bring the milling center into FDA compliancy by documenting all aspects of the manufacturing process, Harris had two options for actually producing the end product. One was to obtain his own FDA clearance as a 510(K)-cleared manufacturer. That process would be time-consuming and burdensome. “To get our own 510(K) clearance to mill CAD/CAM customized abutments, we would need to would need to go through an in-depth testing and validation process that includes fatigue testing, reverse engineering, sterilization validation, and so on.” The expense and time to go through this testing and validation process is extensive and much of it has to be done on every platform within the 510(K). Often new 510(K) holders start out with only a couple of implant abutment platforms in their first submission. “If I wanted to mill a custom implant abutment that interfaced with another major implant system, I would need to repeat much of whole process over again in a new 510(K),” says Harris. “I began to search for another pathway that was less expensive and onerous to execute and one that placed less burden of liability on our facility.”

The second option was to become a contract manufacturer for a company such as BioHorizons that has a 510(K) clearance on the abutment milling blanks. “It has become apparent that the contract manufacturer business model is a viable alternative to obtaining your own 510(K),” says Brown. The arrangement between a 510(K) holder and contract manufacturer for producing end product has existed for many years in other medical manufacturing arenas such as in the pharmaceutical industry. A large drug developer, for example, could outsource the production of a specific medication to one or more manufacturing companies with the appropriate equipment, materials, and a 510(K)-compliant QMS manufacturing process in place.

“It’s an open source arrangement that is just now becoming more common for dental laboratories,” says Brown.

With a fully implemented QMS, a laboratory could easily become a contract manufacturer for a number of 510(K) holders if the 510(K) holder supports that business model.“The interpretation we have from the FDA is if the laboratory has a QMS in place and is milling a 510(K) approved product, then a laboratory would be able to restore on those 510(K) products,” says Torbensen.

For laboratories and milling centers, it is a pathway to produce cleared CAD/CAM abutments, leaving a majority of the obligatory testing, documentation, and compliance burden in the hands of the 501(K) holder. It is the holder’s responsibility to ensure the compliancy of their laboratory partner Class II medical device manufacturer. The supplier of 510(K)-compliant abutment milling blanks is required to audit its contract manufacturing partners annually to ensure the end product meets FDA 510(K) specifications and that FDA compliancy of the manufacturing partner’s QMS is being followed. Although there are currently only a handful of companies that supply cleared 510(K) abutment milling blanks to the laboratory industry on a contract manufacturing basis, Brown believes this type of pre-packaged solution is a business model many laboratories can embrace and will become more commonplace in the future as more 510(K) abutment holders appear on the market.

It is a pathway that Harris embraced and has been pursuing vigorously. His first hurdle was to establish and implement an airtight QMS system customized to his business. “We installed an inventory control system that tracks not only lot numbers, but also individual product numbers for each item within the lot for traceability from case entry to delivery to the client. Received inventory is tightly controlled, tracked, and separated from other inventory or product. It goes into quarantine if it is deemed not acceptable during any inspection process and has to be held separate from everything else in the building. The machinery and processes have all been validated and verified and all processes and procedures in the production chain documented from changing out a milling bur to the technician signing off on that procedure. I now have an FDA-compliant QMS system in place that allows us to mill any 510(K)-cleared CAD/CAM abutment blank on the market should we choose to become a contract manufacturer for that 510(K) holder.”

Torbenson believes that as FDA oversight of CAD/CAM processes increases, it will be necessary that laboratories have a QMS in place to prove they are following good manufacturing practices using CAD/CAM technology. Because most custom abutment processes have transitioned from manual to automated production and are now manufactured using a computer-based CAD/CAM workflow, dental laboratories and milling centers are being viewed as medical device manufacturers of Class II medical devices under the existing Title 21 CFR 820 guidance. As medical device manufacturers, laboratories should understand that the FDA wants to ensure they are adhering to good manufacturing practices by requiring laboratories of all sizes to incorporate a QMS.

“Laboratories have traditionally never had to bear the responsibility for tracking procedures and processes in house,” says Torbenson. “For facilities manufacturing custom abutments for dental implants, a QMS requires the laboratory to document procedures and processes and have that documentation readily available should the FDA decide to stop by and audit the facility.” That would, Torbenson explains, require laboratories to document, among other things, the case as it is entered into their case tracking software, the calibration of their mills according to manufacturer recommendations, and indicate that they are changing the tooling in appropriate time sequences as dictated by the mill manufacturer. “As laboratories should be doing now, they will continue to track components, materials, lot numbers, etc, when the case is finalized and delivered to the dentist, providing traceability should there be a problem with device performance.”

Protecting the patient from harm is the responsibility of all those involved in dentistry’s manufacturing supply chain—from the makers of the materials, parts, and equipment used to those assembling the final finished product. It is incumbent that all players in the supply and manufacturing chain ensure that what they are using to produce the end product and how they are producing it are safe for the patient.

As the industry continues its transition from manual to automated digital workflow, there are those who speculate that FDA oversight might also come to apply to products once considered exempt. That’s because traditional manufacturing processes used to produce handcrafted end products could not be quantified or strictly regulated. However, today’s digital workflow manufacturing produces a digital record that can now be meticulously tracked, verified, and traced. And that fact is not lost on the agency charged with overseeing and regulating the medical devices being placed in patients’ mouths. In the end, the dental industry is just as invested in protecting the patient as the FDA. Just as new technologies, processes, materials, and procedures change how we manufacture our products, FDA regulations may also need to change to keep up.

IDT reached out to the FDA for guidance on several key questions surrounding the issue of using CAD/CAM technology to mill custom abutments and the abutment interfaces, as well as other devices that may trigger further regulatory standards. To help clarify the agency’s current position surrounding compliance issues, Stephanie Caccomo, Press Officer, Office of Media Affairs, US Food and Drug Administration, provided these answers to our queries, which offer insight into how FDA is applying existing regulations to CAD/CAM production of medical devices.

IDT: Traditionally, laboratories have hand fabricated implant abutments through casting or other processes. What issues have led the FDA to scrutinize the automated processes currently being used?

FDA: Hand fabricating by the traditional dental laboratory processes of lost-wax casting with gold alloys and hand milling are well-understood processes. Additionally, these processes are adequately described in the FDA cleared instructions for each dental implant abutment. Finally, FDA-cleared UCLA dental abutments do not include the design, fabrication, or creation by a dental laboratory of the abutment-to-implant connection platform.

The FDA continually reviews final, published guidance documents to determine whether updates are necessary. The most recent FDA guidance for endosseous dental implant abutments is [from] 2004. Additional information for device description and performance testing provided to demonstrate substantial equivalence for abutments may also be found by reviewing the publicly available 510(K) Summary for each cleared device under product code NHA (endosseous dental implant abutments) in the FDA database at insidedentaltech.com/idt969.

IDT: Under what circumstances can a laboratory CAD and/or CAM mill an implant abutment and what FDA requirements/compliance issues are at play?

FDA: Based on recently cleared dental implant abutments, as found under product code NHA (endosseous dental implant abutments) in the public FDA database, a dental laboratory may CAD/CAM mill the top-half of an implant abutment (excluding the abutment-to-implant connection platform) if using a titanium blank or titanium base (ti-base) and following the FDA-cleared indications-for-use statement and labeling provided by the manufacturer. The labeling will include identification of the validated scanner, validated CAD software, validated CAM software and equipment (mill, tools, etc), set-up and maintenance schedule for the CAM equipment, and the ceramic material for the top half of the abutment and fixation cement (for ti-base abutments).

Alternatively, a dental laboratory may become a device manufacturer and may CAD design and CAM mill an entire implant abutment if the dental laboratory holds a 510(K) marketing clearance for the abutment or is a contract manufacturer for a company which holds a 510(K) marketing clearance for the abutment, and follows all applicable pre-market and post-market requirements for a Class II medical device.

IDT: Are there other CAD/CAM laboratory-fabricated products that may be in the future or are currently under scrutiny by the FDA such as implant surgical guides, orthodontic aligner trays, etc?

FDA: Implant surgical guides are Class I-exempt medical devices under 21 CFR 872.3980 (product code NDP) for which the design and manufacturer fall under appropriate FDA pre- and post-market regulations for Class I devices. Orthodontic aligner trays are Class II medical under 21 CFR 872.5470 (product code NXC) for which the design and manufacturer fall under appropriate FDA pre- and post-market regulations for Class II devices.

Dental laboratory exemption under 21 CFR 807.65 does not include the manufacture of medical devices in place of a registered and listed manufacturer.

IDT: Given the fact that there are automated milling units and 3D printers being actively marketed and sold to manufacture abutments, surgical guides, etc, how is a laboratory to know if these are acceptable products to purchase and use? Do resellers or marketers of these products also have to pursue clearance with the FDA to market them? Do they have to disclose to customers that additional regulatory steps must be taken to use the equipment for these purposes?

FDA: Milling units for endosseous dental implant abutments will be validated by the holder of the 510(K) for the abutments and will be identified in the direction for use for the abutment. Companies marketing milling units and 3D printers specifically for the creation of medical devices, at locations other than registered and listed manufacturing sites, should follow the necessary pre-market regulations, such as submission of a 510(K). However, the FDA does not regulate marketers of equipment to be used on the floor of a manufacturing location. Lists of 510(K) cleared devices, as well as registered manufacturers and their listed devices, may be found on the public FDA database webpages, respectively:
 insidedentaltech.com/idt969
 insidedentaltech.com/idt970

IDT: Will the increased use of automated manufacturing and technology in the dental laboratory spur scrutiny of other laboratory-produced products that previously have been exempt?

FDA: The change of manufacturing from traditional dental laboratory processes to the use of CAD/CAM may exceed the limitations of exemption for certain

Class I or Class II regulations, which are identified in 21 CFR 872.9. Additionally, a dental laboratory not following the directions for use provided by a medical device manufacturer which may include specific information for CAD/CAM may exceed the dental laboratory exemption 21 CFR 807.65.