Radiation Levels in Millable Zirconia Materials (Regulatory Standards CE)

Humans are exposed to radiation sources just by walking outside on a sunny day and from naturally occurring radionuclides (atoms that have excess nuclear energy).¹ Mutagenic or transforming effects that are harmful to health occur when the radiation dose exceeds a certain limit.² Patients, as well as dentists and dental technicians, are predisposed to radioactive contamination when exposed to dental ceramics containing radionuclides.³

Many of the minerals mined from the Earth contain low levels of radioactive elements such as uranium, thorium, radium, zirconium, and phosphate. These naturally occurring radioactive minerals (NORMs) are subjected to a number of manufacturing processes—which are themselves overseen by a number of regulatory agencies⁴—that differ depending on their intended use. Some of these processes subject the ores to radioisotope enrichment referred to as technologically enhanced natural radioactivity (TENR).⁵ Enhanced natural radioactive sources can come from coal-fired power plants, uranium mining, fertilizer production, and mineral sand processing plants producing zircon. In the early 1980s, Boothe et al⁶ began investigating zirconium ore as a source of TENR. Biasini et al⁷ and later Beretka and Mathew⁸ reported finding high concentrations of natural radionuclides in zircon ores. These radionuclides produce three types of radiation: alpha (a helium nucleus—two protons and two neutrons), beta (an electron), and gamma (high-energy photon).⁹ These radioactive impurities found in zirconium dioxide must be taken into account when used for medical and/or dental purposes.¹⁰

In the early 1970s, dental ceramic materials lacked fluorescence. To mimic the human tooth’s fluorescent characteristics, manufacturers used additives that also happened to increase the radioactive potential—uranium and cerium.¹¹ Porcelain denture teeth in the 1960s and 1970s also had uranium oxide additives for the fluorescing effect and because they could withstand high temperatures during the porcelain baking process. Ceramic porcelains for single crowns and fixed partial dentures had radioactivity levels 4.2 times greater than background radiation.¹² Although the radioactivity levels were higher than the standard, a patient would have to swallow 60 pulverized crowns per week in order to reach the threshold value of absorbed radioactive substances.¹³ Still, the dental technician was exposed to a continuous source of radioactive material through the ceramic dust. Anusavice¹⁴ stated that the technician would have to swallow at least 300 grams of porcelain powder per week to go beyond the limit set by the International Commission on Radiological Protection (ICRP).

In 1981, voluntary regulatory guidelines were established for manufacturers not to increase the radiation levels beyond the naturally occurring levels of the minerals used in the production of ceramic powder.¹⁵ In 1991, the American Dental Association/American National Standards Institute (ADA/ANSI) Specification No. 69 discontinued the use of uranium in dental ceramic materials.¹⁶

Radiation: Units of Measurement

Radiation is measured by a substance’s level of radioactivity, the human absorption dosage, and the quantity absorbed. When radioactive substances decay (disintegrate), ionizing radiation is emitted. The decay mechanism is when the nucleus of an unstable atom spontaneously discharges a particle (alpha, beta, or gamma). A substance’s level of radioactivity is measured according to the number of nuclei-releasing particles per unit of time. The standard international unit (SI) is called a becquerel (Bq)—named for Henri Becquerel, who discovered radioactivity.¹⁷ One becquerel equals one particle discharged from a substance per second. Radioactivity is measured in terms of unit weight of a substance by becquerel per gram (Bq/gm). The term curie is also used as a measurement unit of radioactivity based on the number of particles discharged from a substance per second in one gram of radium-226 (37 billion per second). Therefore, one curie is equal to 37 billion becquerels.¹⁸

A sievert (Sv) is the unit dosage of ionizing radiation that a human can absorb, measuring the biological effect of that dosage on a human cell. The sievert unit measures the risk of the effect of external radiation from sources outside the body. It is not, however, used to relate the severity of acute tissue damage that will occur.¹⁹ A rem (acronym for Röntgen-Equivalent Man unit; used in the US but obsolete elsewhere) can be interchanged with sievert, with 1 sievert equaling 100 rems.

The unit gray (Gy) or rad (100 rad = 1 Gy) is used as a measurement of the physical quantity of an absorbed dose of radiation (eg, an X-ray) and is defined as the absorption of one joule of radiation energy per one kilogram of matter.²⁰ Grays are used in areas of nuclear technology that do not involve living things and sometimes in radiation biology research.²¹

Radiation Safety Levels

In the early 1990s, concerns were raised over the radioactive impurities found in zirconium ceramics intended for medical and dental applications. The safety in these materials can be surmised as being biocompatible if they are nontoxic to the immune system and do not induce inflammatory, allergic, mutagenic, or carcinogenic reactions.^10,19 Due to the crystalline nature of zircon, removal of uranium and thorium is difficult to achieve without destroying the crystal lattice.²² Several different methods are employed to reduce the amount of radioactivity to a safe level, using different mineral and organic acids in aqueous solutions to leach out the radionuclides. For example, leaching with acetic, hydrochloric, and nitric acid was found to be effective in reducing beta activity up to 36%.²³ Sulphuric acid heated to 150°C has been shown to remove 28% uranium and 47% thorium. After the purification process, the level of uranium concentration in zirconia powder should range between 0.001 and 0.007 Bq/g and not exceed a maximum level of 1.0 Bq/g (ISO 6872).²⁴ According to the American Society for Testing and Materials Standards (F1873), the acceptable level of mass radioactivity of surgical-grade zirconia should be lower than 200 Bq/kg or 0.2 Bq/g.²⁵

Today, the source of radiation in dental restoratives is naturally occurring and consists mostly of alpha and gamma emitters. The alpha particles are more toxic than the gamma particles but are limited to a range of 30 microns; therefore, they may be absorbed by saliva and plaque present on the restoration before reaching radiosensitive cells in the basal layer of the oral mucosa.¹⁶ Veronese et al16 reported that, even though higher levels of gamma radiation were measured in feldspathic porcelain and were related to naturally occurring potassium-40 (40K), the activity concentration was still below the threshold limit for 40K (10 Bq/g). Inadvertent tissue damage to the oral mucosa may occur during intraoral ceramic crown adjustments, which can result in more exposure for the patient by means of open tissue penetration and swallowing.²⁶

The manufacturing processes used to produce zirconia milling materials are critical to the health of the dental technician, the dentist, and ultimately the patient. All parties can be affected if the zirconia has not been processed using effective removal methods to reduce radioactive impurities to safe levels.²⁷

Classification of Medical Devices

All medical devices sold in the United States are regulated by the FDA. Over the past 50 years, the FDA has established a number of approval or clearance systems for various medical devices depending on their classification. There are now three classifications of medical devices based on their risk potential. Class I medical devices pose no potential risk. This classification includes such items as dental floss, tongue depressors, elastic bandages, handheld dental instruments, and examination gloves. Class II medical devices are more complex in design but pose only minimal risk. These devices require special labeling, mandatory performance standards, and post-market surveillance. Examples of Class II medical devices include X-ray machines, powered wheelchairs, infusion pump surgical needles, and intraoral sleep apnea appliances. Finally, Class III medical devices have a more intricate design and are subject to the strictest guidelines because the potential risk is the highest. In addition to following the same guidelines as Class I and II medical devices, Class III medical devices must be pre-market approved by the FDA and require scientific review before market availability. The main difference with these devices is that they support or sustain human life and any malfunction is absolutely unacceptable. Examples of Class III medical devices include implanted pacemakers, heart valves, and implanted cerebral simulators.²⁸ Class I and some Class II devices do not require FDA review to provide reassurance of safety and effectiveness before marketing to the public. These products are 510(k) exempt.

FDA and the 510(k): “Cleared” vs “Approved”

In 1938, Congress passed “The Food, Drug, and Cosmetic Act,” which is a set of laws giving the FDA authority to oversee the safety of food, drugs, and cosmetics. Today, an FDA subcommittee, the Dental Devices Panel (DDP), reviews and evaluates data concerning the safety and effectiveness of marketed and investigational products for use in dentistry, endodontics, or bone physiology relative to the oral and maxillofacial area and makes appropriate recommendations to the Commissioner of Food and Drugs. For example, the DDP classifies intraoral appliances for snoring and/or obstructive sleep apnea as Class II medical devices. These appliances treat a medical disease and are covered by only medical insurance and Medicare, not by dental insurance. Therefore, any device claiming to treat a medical disease must be registered with the FDA, including payment of annual fees.²⁹

The Medical Device Amendment of 1976 created the 510(k) process. At the time, the intent of this process was aimed at low- to moderate-risk medical devices. According to classaction.org, a nonprofit organization that reports on medical class action lawsuits, the 510(k) process is being used to approve much higher-risk medical devices.

Section 510(k) of the Food, Drug, and Cosmetic Act requires an inventor to notify the FDA of the intention to market a new medical device at least 90 days in advance. The FDA allows two regulatory pathways for the marketing of medical devices. The most common path is the 510(k) process. To gain 510(k) clearance, a new medical device must demonstrate to the FDA that it is “substantially equivalent” to a previously legally marketed device. The FDA will then “clear” the device for marketing. A vast number of devices are marketed through this process. Clinical trials are usually not required through this pathway, but testing and documentation may be required.

The other regulatory pathway for new medical devices is the pre-market approval process. Obtaining FDA approval for a new device is more expensive than the lower-cost 510(k) clearance process. Approval of a new drug requires the submitter/requester to present clinical trials before marketing approval is granted.³⁰

Regulating Imported Dental Products

The FDA established the Quality System Regulation (QSR) code (21 CFR Part 820) in 1997. This code recognized Good Manufacturing Practices (GMP) for manufacturers to regulate imported dental items. In 2004, the National Association of Dental Laboratories (NADL) became involved when the FDA established that all dental laboratories must comply with 21 CFR Part 820. Failure to act in accordance with the regulation would be determined by FDA audits, which could result in various corrective steps and/or fines for violations. The NADL adopted and adapted the Dental Appliance Manufacturers Audit System (DAMAS), a recognized third-party standard of certification that complies with the FDA’s Quality System Regulation. Presently, DAMAS is the dental industry’s most widely acknowledged certification system that accounts for the hiring of competent employees and equipment maintenance, as well as the use of FDA-approved materials.³⁰

In order for foreign manufacturers to import medical devices into the US, they must complete the FDA medical device approval process. This starts with the foreign manufacturer submitting an application to register as an establishment. The required information would include the proprietary name (eg, XYZ zirconia milling block), the regulation name (such as “porcelain powder for clinical use”), the regulation number (872.6660), and the product code. The three-letter product code (EIH) can be found by researching “predicate devices,” products already registered for the US market.

Additional necessary information includes the intended use, the substantial equivalence (how the product is equal to other legally marketed devices in the US), and a statement of nonclinical testing as to the physical properties complying with ISO standards. Since the proposed device is said to be identical to a previously approved device, biocompatibility tests are not required. The safety and effectiveness of the device must be addressed, but again, the applicant only needs to declare the successful use of products with similar formulations that are legally marketed. The foreign applicant must also designate a United States agent.

The foreign manufacturer must provide proof of compliance to meet the FDA QSR. The FDA, however, does not require a pre-registration audit for Class I and II device manufacturers. Instead, the FDA conducts pre-announced inspections to ensure compliance. Imported medical devices also must meet Bureau of Customs and Border Protection requirements and assess and collect duties, taxes, and fees. However, it is unclear how all these controls are enforced. If a dental laboratory purchases zirconia milling blocks from unconfirmed suppliers on eBay, the US government is unlikely to visit those foreign manufacturers to perform inspections.

Once these requirements have been met, the device can be sold in the US. The foreign manufacturer’s website will have the FDA listing that indicates the authority to commercialize the device. There is no expiration of this authorization unless changes are made to the device.

Quality Control and Truth in Advertising

A number of foreign zirconia manufacturer websites list their products along with various certifications and permits to attract prospective buyers. Some of the listed information may not be legitimate. They may list “ISO 13485 certified,” a standard that describes a Quality Management System (QMS) for the manufacture of medical devices; all manufacturers of FDA-cleared medical devices are required to implement and follow either a QMS or the FDA’s QSR. According to the global medical device regulatory consulting firm Emergo in Austin, Texas, the ISO 13485 certification can take from 4 to 7 months and requires annual audits to maintain the certification. ISO 9001 is another standard that may be found on the manufacturer’s website. This designation provides assurance that the company meets the needs of its customers while maintaining statutory and regulatory requirements related to the product.³¹ ISO 9001 is issued by an independent third party registered with that country’s health and safety regulatory agency.

The letters “CE” are sometimes marked on a milling block or disc; this is the abbreviation of the French phrase “Conformité Européene,” which literally means “European Conformity.” A CE marking on a product is the manufacturer’s declaration that the product complies with the essential requirements of the relevant European health, safety, and environmental protection legislation. This designation allows the product to be sold within the European Free Trade Association (EFTA) and the European Union (EU). Wellkang® Tech Consulting Group, a British/Chinese business-to-business regulatory company, reports the misuse of fake CE conformity markings on products sold overseas.

In many countries, the importers, rather than the manufacturers, are held accountable for ensuring the proper regulations were followed in the development of these materials and “devices.” The importer of products sold into EFTA and EU countries is responsible for regulatory compliance. The same is true in the US, where the Consumer Product Safety Commission (CPSC) regulates consumer product safety. The CPSC also considers the importer of goods from China to be the manufacturer, meaning that the importer assumes all responsibility. One may purchase zirconia milling blocks through Amazon’s “Fulfillment by Amazon” program, but the importer is responsible for the quality and safety of those materials, not the manufacturer in China.

A product from China may be labeled with “SFDA,” the acronym for China’s former state food and drug administration. However, in 2013, the Regulatory Affairs Professionals Society—a neutral, non-lobbying nonprofit organization—reported³² that the agency underwent reorganization due to scandals of corruption for taking bribes in return for approving substandard medicines. The agency was renamed the China Food and Drug Administration (CFDA) in 2013.

In January 2016, the British newspaper The Guardian issued a warning to dentists in the United Kingdom concerning the rise of counterfeit products and equipment on the market. The Medicines and Healthcare products Regulatory Agency (MHRA) reported that most of the counterfeit products came from China and Pakistan and were sold through such online marketplaces as Amazon, eBay, and Alibaba. Enforcement officials found that online sales of the counterfeit equipment sold for only a fraction of the price of legitimate items. They also said that the makers of the counterfeit equipment are very sophisticated; their method is to take modern, up-to-date equipment and re-manufacture it at a much lower quality—down to copying even the CE markings, instructions, logos, and packaging.

One often overlooked way to identify fake materials is the price. Currently, genuine high-quality zirconia powder is sold for approximately $100 per kilogram. One kilogram will produce two 98 mm milling disks. Online pricing from Chinese importers found on Alibaba can be as low as $30. Prices so low leave questions as to the quality of the material. The Tosoh Corporation, the largest supplier of zirconia powders in the world, offers free testing to confirm or deny the presence of its powder in a zirconia sample. It must also be understood, though, that Tosoh sells and tests only the zirconia powder. The manufacturer is responsible for the fabrication of the milling block or disc, and all fabrication processes are different.

Accountability: Dental Laboratory Registration and Disclosure

The goal in dentistry is to provide the best care to the patient, which includes delivering high-quality restorations prescribed by the dentist and fabricated in the dental laboratory. Both dentist and patient should have confidence in their expectation that the materials used for the restorations are exactly as prescribed. As of November 2013, the ADA adopted a policy urging all state dental boards to require that dental laboratories register with the state and provide disclosures to the dentist about the point-of-origin and the content of materials used in restorations. Some states already required registration; for example, South Carolina enacted such a law in 1942, while others began to follow a few decades later (Kentucky, 1977; Texas, 1985; Florida and Pennsylvania, 1987; Oklahoma, 1992; and Minnesota, 2012). Five states require material disclosures and/or point-of-origin disclosures—Florida, Kentucky, Minnesota, Ohio, and South Carolina. These steps do, in fact, protect the safety of the patient—they reduce or negate the economic incentive of using less expensive, likely counterfeit materials. If laboratories violate these laws, they risk the loss of their registration and ability to conduct business in that state. In the age of a global economy in which restorative materials with varying degrees of quality are available worldwide, regulations can protect the patient.

Conclusion

Processes for making zirconia powder require careful adherence to ensure safety and high-quality products. Industry practices are in place to protect the patient, dentist, and technician from significant radiation exposure, as well as to guarantee the best possible results. Legal regulations already exist in several states.

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