Dental Biomaterials Standards and Quality Assurance

Dental Biomaterials Standards and Quality Assurance

Internal and external quality assurance are essential procedures required to ensure the materials put on to the market are fit for purpose and safe for usage. International, British and European standards all provide different levels of external quality assurance for their members. Following standardised procedures provided by such standards can have benefits as well as downfalls, which are discussed more in depth in this essay.    

This essay critically appraises International, British and European standards and aims to show methods of testing, the process required to accept new dental materials onto the marketplace and how British, European and worldwide production methods are underpinned by scientific research and applied quality assurance.

Quality assurance of a material is the keeping up of a desired level of quality in each stage of its production. [Manghani. K, 2011]. In order to quality assure businesses and their produced materials, internal quality assurance by authorities such as Medicines and Healthcare products Regulatory Agency (MHRA), Medical Devices Directive (MDD) and the use of audits is needed. The MHRA  ensures that medicines and medical devices function as they are supposed to and are safe for usage. [Abozguia.K et al, 2007]. The MDD are issued by the European Economic Commissions and regulate the performance and safety of medical devices. However, external quality assurance is done by conformity to set standards such as British Standards (BS), International Organisation for Standardisation (ISO standards) and European standards (EN). [Matysek.A, 2014].  ISO was issued in the 1950s and is an association of national standards bodies which works towards ensuring the safety, reliability and the quality of materials/products. [Warburton.K et al, 2011]. They provide protocols to ensure that materials are fit for purpose and meet predetermined standards, preventing non-conformity. [Burnet.D,2015]. British standards were issued in 1903 and are specification of recommended procedures, developed and published by the British Standards Institution (BSI). BS are made by a process including a committee, consultation and consensus, which strengthens the authority of the standard and ensures its acceptance by a wide range of individuals interested in its appliance. [BSI,2018]. However, ENs are documents that have been approved by one of the three European Standardisation Organizations; CEN, CENELEC or ETSI and provide standards that help advance the Single European market. Its members include all 28 members of the European Union (EU). [Matysek.A, 2014]. If the production procedure of a material follows BS, a Kitemark will be applied on to it. The BSI Kitemark emerged as the BS Mark in 1903. Manufacturers with the BSI Kitemark are part of a privileged club of the world’s best brands/companies. A BSI Kitemark on a material/product evidences that it conforms to a certain standard. Currently, there are over 2,500 BSI Kitemark licences. [Ware.J,1986]. However, if EN standards are followed, a Conformité Européenne (CE) mark would be applied. CE marks are conformity marks which all European medical devices must have before their placement on the market. It is seen as an evidence that the product meets all the specifications of the relevant legislation including ones which are safety related. [Mowat.E et al, 2012]. In 1998, compliance to MDD became compulsory for all medical devices placed in the European market. Therefore, it is required of manufacturers to fulfil various requirements resulting in the placing of the CE mark on their devices. [Bentley.D, 1999].

ISO is an international standard which provides worldwide usage. It is written under strict regulations with participation of representatives from all around the world and once released, it will be available to be handed out to the public. However, an EN document is a standard which is regional and is only intended to be used in the EU. It is written under regulations with participation from only the representatives of the member states. Once released, it will not be available to be given out to the public. On the other hand, a BS-EN document is a national standard which is published as each country in Europe adopts the EN document. There are strict specifications for the abandonment of any duplicating or conflicting standards. [Tari.J et al,2012]. Another area of comparison is adoption. When an ISO document is released, it is the right of countries to republish the standard as a national adoption.  Therefore, the EU has the right to adopt and re-publish it where they also add a level of regulatory overhead. As a result, the issue date of the EN adoption is later than the original ISO document as well as having additional information on the cover sheet. Also, English, German and French copies will be supplied to each EU member. However, the BSI publishes the official English language edition, the German Standards Institute (DIN) publishes the official German language edition, and the French publishes the official French language edition. Such national adoptions will have different issue dates as the regulatory time to assess national standards for any withdrawals. [Simoes.M et al, 2016]. Another area of comparison is certification. The EN editions of all standards are mentioned in the EU’s schema of regulation, therefore only EN standards are accepted by certification professionals when assessing customer practices / facilities. Z Annexes are also included in the EN edition, which impacts the understanding of how the information in one harmonised standard relates to the directive related to it.  This means that if one’s partner in trade in the EU is in Germany and they want their auditor to be from a German company, it would be beneficial for them to get the English editions of the DIN-EN standards. [Batch.C, 2011]

In addition, ISO can improve the production process of materials and optimise the performance in businesses. It also helps handle risks while enabling organisations to work more efficiently. In addition, it supplies businesses with client credibility, which shows the company’s commitment for providing quality to its customers. [Cots.S et al, 2016]. ISO’s certification process also brings attention to self-reflection, which encourages communication amongst internal areas of companies. It would also help businesses save money and reduce their waste. [Tari.J et al,2012]. However, ISO requires excessive amount of money, time and paperwork for registration. Its members can also only get as much participation in the standards and introducing a new material as the amount of money they pay. Therefore, genius new ideas may be pushed to the side if there is a shortage in money. Following ISO procedures can also decrease productivity by demanding actions which are unnecessary. In addition, owners may not have a sufficient understanding of the standards, which can lead to wasted time/effort. Also, the certification process can also take a very long time to complete or even shift from the early phases of the process to the portion of the ending audit. [Santos.L, 2001].

ENs have led to the collaboration among countries with the aim of reaching common grounds on common documents about how to act in various sectors. This harmonisation brings about a Single Market which eliminates technical barriers of trade. Also, for products which are not CE marked, ENs encourage the use of test results performed in one country. That means the removal of trade barriers because a main item of the CE marking is the free circulation of CE marked products on all Europe. The use of a harmonised classification standard also means that all countries can have the same understanding of the product specifications and the methods of testing. From the point of view of manufacturers, having a harmonised standard of testing a product in one country, would mean that the CE mark gained in a European country would be valid in all of Europe, which saves costs by removing the need for repeated tests in every country. [Matysek.A, 2014]. On the other hand, purchasing band new equipment has elevated the prices of tests, when compared to the prices arranged on national levels. [Castillo.S, 2018]. However, BS help boost UK’s productivity, improve performance and support UK’s international trade.  BS also play a crucial part in the strength of UK industry as well as support the growth of economy. [BSI,2018].

Taiwan is a country with no representation in ISO under any membership class from 2015. The Bureau of Standards, Metrology and Inspection (BSMI) covered by the Ministry of Economic Affairs (MOEA) is in charge of the assembling of “Chinese National Standards” (CNS), as well as for conformity assessment. They perform material inspection measures and draft regulations and standards policies. Products identified by MOEA must comply with the inspection requirements prior to their shipping from the manufacturing premises and placement on the market. Testing of Taiwanese CNS standards and the issuing of product test reports are available to manufacturers worldwide to enhance the safety of their products. [US Commercial service, 2016].  Due to not being an ISO member, Taiwan may not be able to trade ceramic materials with countries with an ISO membership, as the standard and quality of the materials would not meet the level of their standard and quality.

ISO 6872:2015 specifies the requirements and test methods for dental ceramics. Before ceramic materials are put out on to the market, in vitro and in vivo tests need to be carried out. For the quality approval of ceramics, this ISO states that there are two samples (type 1 and 2 ceramics) which need to undergo in vitro mechanical (flexural) tests. It states that three flexural strength test methods (three and four-point bending and biaxial flexure) should be carried out. Chougule.K et al evaluated the effects of alteration of the surface on Monolithic zirconia’s flexural strength. Thirty rectangular zirconia samples were prepared by CAD-CAM and divided into 3 groups: no alteration, ground/polished and ground/reglazed. The number of samples used is the same as recommended in the ISO, which adds to the reliability, accuracy and validity of the results. However, the dimensions of specimens were according to ADA specification for flexural strength testing of dental ceramic and not ISO. Therefore, it takes away from the validity and reliability of the result. Flexural strength testing was performed with a three-point bend test on a universal testing machine. This method of testing is the same method as recommended in ISO, which again, adds to the accuracy and reliability of the results, as standardised methods of testing was used.  The mean flexural strength of the reglazed group was much higher in comparison to the control or polished groups. The calculations of the mean fracture strengths were done using the equation which is recommended by the ISO 6872 standard, 1995. Although the use of ISO’s equation suggests reliability, an old version of the ISO 6872 was used, which may take away from the accuracy of the results. However, the publication date is very recent, which means the information provided is up to date which adds to the reliability of the results. 22 references were also used, which evidences the results obtained and the information provided. [Chougule.K et al,2017]

However, Marrelli.M et al carried out an in vitro study where the mechanical strength and the surface hardness of yttriumm- doped zirconia (Y-TZP) were examined. According to a procedure from this ISO, 4 types of zirconia specimens were examined. Therefore, this adds to the validity and reliability of the results, as standardised procedures from the most up to date version of ISO was used. Two-layered zirconia-veneer specimens were also used for three-point bending tests. This is the same test method as stated in ISO, therefore, it again evidences conformity to standardised procedures, showing the reliability of the results. A strong effect of the surface roughness was found on the mechanical strength of zirconia specimens.  [Marrelli.M et al, 2013]. The conclusions of this study (surface roughness can highly impact mechanical strength of the Y-TZP ceramics) can help the scientific community move forward and impact the development of dental ceramics. Its recent publication date also means that the provided information and results are up to date. In addition, the dimensions of the specimens used (length (l) = 25 mm, width (b) = 5 mm, and thickness (t) = 2 mm) was according to ISO 6872, which adds to the accuracy, validity and reliability of the results. However, the study has a fairly low number of references (17). This can mean that their research is potentially of low impact to other researchers as they may struggle to expand their knowledge due to a lack in references. The study was also supported by Tecnologica Srl which may mean that the results have a level of biased. This study follows more of ISO procedures and specifications, therefore it can be suggested that its results are more reliable and valid.

Cytotoxicity tests are a type of biological evaluation and screening tests which include the use of tissue cells in vitro to observe the cell growth and morphological effects. [Li.W et al, 2015]. ISO 10993-5:2009 is in charge of cytotoxicity test procedures for dental materials, where it states the procedure for direct contact method between materials and incubation of cells at 37 °C. The agar diffusion assay enables the lysis of cells on a layer of agar where the effect of the material on the cells can be examined. [Liu. X et al, 2018]. Safety data sheets suggest that ceramic materials do not have taxological hazards. [DATA SHEET]. Sharbeha.H. et al, also assessed the in vitro cytotoxicity of dental porcelain. The responses from cells of human fibroblast cell lines were analysed after incubation with the porcelain. It was found that the material produced a slight suspension of succinate dehydrogenisation and this is seen as clinically acceptable, which suggests it is not cytotoxic. [Sharbeh.H. et al, 2012]. The tests were carried out in accordance to ISO 109935 which shows the reliability and validity of the results. The study also used appropriate cell lines due to being accepted in the international platform, which adds to the reliability of the results. The method of testing was also a direct test, which is the same one mentioned in the ISO. This again adds to the reliability and validity of the results, as standardised methods of testing were used.  Its recent publication date also means that the provided information and results are up to date, adding to its reliability value. The use of 23 refences also means that the results are reliable and based on well researched research.  However, Kilcik.K et al carried out an invitro study and evaluated the effects of various types of all-ceramic substructural materials to determine their biological performance in experimental conditions. Six all-ceramic systems were used. However, ISO states at least 10 should be used, therefore it takes away from the accuracy and reliability of the results.  Cell-culture tests were conducted with the use of a direct-contact method according to ISO 10993 specifications. In addition, the surface area to volume ratio of the specimen in the cell-culture medium was 65 mm/mL (50e600 mm/mL, which is in the ISO-recommended range). This adds to the reliability and validity of the results, as standardised procedures and specifications were used. It was found that all-ceramic materials are not equal regarding their in vitro biological impacts or aging. In addition, Finesse and Zirkonzahn all-ceramics did not present any signs of cytotoxicity. The use of 32 refences also suggests that the information provided can be relied on. Lastly, the recent publication date also means that the information and results are up to date and can be relied on. [Kilic.K et al, 2013].

In vivo studies such as animal tests may then be carried out. ISO 10993-10:2013 is in charge of biological evaluation of medical devices. [REFERNCE ISO] Animal testing in the UK was banned in 1998, and in vitro tests are currently more relied on. However, Europe stopped in 2013 and since then, animal tested cosmetics products can no longer be sold even if the testing is not done in Europe. Since then, many companies have stopped testing on animals for cosmetics purposes. As a result, more effective and superior non-animal methods have taken over. [Badyal.T et al, 2014]. Scarano. A et al examined the bone response after implanting zirconia ceramic implants in the eye socket of 5 albino rabbits. (Same species and number of animal as stated in ISO which adds to the accuracy and reliability of the results obtained.) The proliferation of fibroblasts and vascular invasion were observed in the final weeks in addition to the growth of the tissues in the implant pores. The rabbits were also anesthetised as recommended in ISO. Therefore, it means standardised requirements were conformed to, adding to the validity a reliability of the results and shows that study followed ethical procedures to ensure pain inflicted to animals was reduced. Fibroblast proliferation and vascular invasion were observed by the final weeks in addition to tissue growth in the implants pores. No rejections of the implants were observed which suggests that ceramics are biomaterials which provide good osseointegration for use in the oral cavity. [Scarano.A, 2003]. The results may help kick-start the use of this material in clinical trials to examine the effects on human live tissues. However, the publication date is fairly old (2003), therefore the findings may not as up to date with the new developments. In addition, 36 research articles were referenced which proves the findings and shows the reliability of it. In an in vivo study by Mostafa.D et al, zirconia implants were placed in femur head of rabbits, and evaluated the percentage of bone–implant contact (BIC). A majorly higher BIC% was found around HA–bioactive–hybrid sand PRP-coated surface in comparison to the control which means that bioactive–hybrid–zirconia implant surface enhances osseointegration of zirconia implants. However, this study did not follow any of the ISO specifications, which reduces the reliability and validity of the results.

As a next step, clinical trials on humans may be carried out to ensure it does not cause any harm to dental professionals and patients. [Macneil.P, 1998]. ISO 10993-1 is used to assess the in vivo function of materials, where it allows skin irritation data to be done directly on humans. [REFERENCE ISO].  Sun. T et al performed a biocompatibility test on human gingival fibroblasts placed into aged and unaged graded nano-g lass/zirconia and yttrium-stabilized tetragonal zirconia polycrystals for 2–72 h (same recommended time as in ISO). Therefore, the fact that ISO procedures were followed adds to the reliability and validity of the results. Human gingival fibroblasts were cultured in Dulbecco’s modified Eagle’s medium. [Sun.T et al, 2018]. Regarding the critical appraisal of this study, the specimens were prepared as uniform plates (1.5 x 1.5 x 0.2 cm) according to ISO, which adds to the accuracy and reliability of the results. In addition, it’s very recent publication date (2018) means that the results and the information provided is as up to date as it can be, adding to the reliability and usability of the results. It also has a high number of references (34) which adds to the validity of the means the information provided and adds to the reliability of the results.

Nevertheless, Further research on ceramics as a material is required. As concluded from Marrel.M et al’s research, it was included that further research on ceramics should be carried out to measure the wear properties of the ceramic veneers, as well as the interaction with natural enamel. Also, in Sun.T et al’s study, it was concluded that their study was a preliminary report, and further in vivo and in vitro studies with more comprehensive test methods are needed to confirm the present results.

It can be concluded that both internal and external quality assurance are essential within dentistry to regulate and quality assure businesses and the materials/products the produce. This is to ensure of their quality and appropriateness for clinical use. It also safeguards the consumers.  In addition, the benefits that standards provide certainly outweighs their disadvantages. Following standardised procedures provided by standards such as ISO also helps carry out studies which obtain accurate and reliable results which can be relied on. It can also be concluded that BS imply the highest level of standardisation and provide the most recognised symbol of conformity (Kitemark), followed by EN which provides a moderate amount of standardisation through its standards and which provides materials/products with CE marking.

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