Characterizing the risk factors for the long-term survival of the Avita bone-level dental implants

Background: Risk analysis file will never be closed in the technical documentation of the dental implants for the marketing purpose. In this paper the most common risk factors categorized as implant-related risks, surgeon-related risks, patient-related risks, and maintenance-related risks in the manufacturing process, application, the long term usage and the so-called survival rate of dental implants are studied. Methods: The importance of any of the potential risk factors directly related to the product or the processes which are indirectly related to the product quality are assessed based on their severity and probability of occurrence. Proper measurement called as mitigations are considered to standardize the risks to the acceptable criteria. Results: The equivalent risk assessment factors are compared in pre-mitigation and post-mitigation stages. The aim was to see whether the factor reduces to the acceptable or conditionally acceptable state for each risk or not. Conclusion: Through this comprehensive study, the risk analysis file is completed however it can be even more complete, in the future, at this industry. In the further studies, discretizing the steps of severity or probability to finer steps, and ultimately converting them to a continuous form would be aimed.

through the manufacturing process is still necessary. There are different factors that are threats for the health of patients when placing dental implants as a root treatment solution. In general, usage of a dental implant is just rational if the benefits overcome the consequences of risk factors. Ultimately, risk analysis helps to provide marketing surveillance. However it has been used a lot for the clinical trials as well [3][4].
Some researchers believe that there are only two main categories of patient-related and implant-related risk factors, which are generally accepted to contribute in the success rate of surgeries [1][2]5]. However, some researchers considered one more aspect of surgeon-related factors which itself is categorized under the implantrelated factors [2]. This is partly because some of the angulated abutments are machined by the surgeons or relevant laboratories from the pre-milled abutments.
There is another aspect to this problem which is related to the maintenance phase.
In the next section, these aspects of the study have been elaborated as the general causes of the failure, where all the factors from the implant design and manufacturing process, to properly placement, and from the post-surgery to longterm survival are covered [6]. Implant-related risks: Implant-related risks mainly originate from the implant design parameters such as dimensions, aspect-ratio (length/diameter), material properties, safety factor and material roughness [6]. In addition, the manufacturing process, packing, storage, and providing adequate information to prevent misuse are also important stages before the surgical process.
Surgeon-related risks: Parameters such as surgeon's measurement from the bone level thickness, soft tissue level thickness, and timing of the surgery stay under the surgeon-related risk factors. Some of the surgeon-related factors are dependent to surgeon decisions and observations such as being adjacent to other teeth or implants [6][7][8][9].

Patient-related risks:
The third category is the patient-related risk factors, which is focused by some other researchers [8][9][10]. Patient-related risk factors cover a wide range of diseases' history in patient. In addition, the current condition of skin, soft tissue and bone, as well as bleeding, smoking, alcohol consumption, the presence of bacterial plaques, and soft tissue volume growth rate are constructive factors in the survival or the failure of dental implants [10-11].
Maintenance-related risks: The next category of the risks called as maintenancerelated factors which are mainly focusing on the post-surgery care and maintenance issues. This category is mainly efficient with the corporation of the patients. Proper instruction and the role of patient is key for achieving higher survival rate from this stage. In this work, although the patient-related factors are more focused by the authors, there is almost no maintenance responsibility lying on the patient yet.
In this research the main aim is to fully study the risk factors related directly to the product quality or indirectly through the processes of manufacturing and using dental implants. In order to formulate the importance of each risk factor, and provide the best surgery strategy, every patient's technical file needs to be documented based on a comprehensive risk analysis [10]. Thus, the risk analysis from the peri-implant stage has been documented. A parameter called in the literature as Equivalent Risk Assessed (ERA) [3] or in this work as risk priority number (RPN) collected and calculated from the severity and probability of the risk factors and have been used largely in this research. And the importance of the risk analysis in technical documentation of the dental implants is highlighted. Finally, the risk factors are characterized, analyzed, and control of the hazardous situations studied in dental implant production.

Results and Discussion
In this study the authors are motivated to assess the risk of the failure at the dental implants for the marketing purpose. To complete the risk analysis mitigations have been implemented to reduce the probability or severity of different risk types.
Different types of risks of the failure of the products, and also the procedures are investigated. In this section, the list of the detected risks has been provided within the Table 1. Table 1 List of the risk factors of the dental implant production. In order to control the risks number 1, 2, and 3, there are two different solutions.
The first one is the process control and the other one is QC (raw material QC and in- Focusing on the process control beside in-line quality control is valuable and in some situations PC is easier than QC. Since counting the particles in the package of final product is hard and time consuming, process control in clean-room is proposed instead of quality control of packaging. This mitigation for risk number 12 reduces both severity and probability since by controlling the process the probability of occurrence is reduced, and by setting a safety factor for accepted amount of particles in the air, the sterilization is with a better quality that reduces the infection severity. Another group of risks are related to labelling and information supplied for the user (risks 16 & 17). Controlling the risks related to labelling is much easier than manufacturing risks. Color coding of packages' door and information supplied to the user is proposed through two labels, one of them on the backside of the cartoon, and the other one inside the blistering pack.
As previously emphasized, regarding the importance of sterility about the risk numbers 11 and 12, there are critical harms behind unsterile product. Therefore, double seal packaging with blister and sealing door was proposed to reduce the probability of loss of sterility during transportation (risk number 15). In addition, the sterility is assured for a definite time, which itself needs an expiry date for each product. To control the risk number 14, the available stocks are systematically controlled in a detection and traceability process. This means that registering the batch number of expired products for invoicing is not allowed in the designed software. But, it is possible that the expiry date pass while the user stores the implant.
For risk number 24, an adjustable torque wrench that slips when the preset torque is reached out is proposed. Thus, no extra torque will be applied to the implant.
Grabbing the implant from capsule pack is prescribed to be done initially by driver with hand, and then tightening it with hand piece or torque wrench. Therefore, there is a risk of dropping implant or other components in the patient's mouth. To reduce the probability of this risk, a driver with high gripping force has been designed.
In addition, the risks numbers of 20, 22, 28, 29, and 30 would be controlled by specific design of the surgical kit. The kit is color coded and the color-based process of drilling is defined for each implant diameter. To control the tightening torque, there is an adjustable automatic torque wrench which bans the applied torque rising from the set amount.
Since the risk number 33 is a surgeon-related risk factor, there is no systematic solution to reduce the probability of the occurrence. Therefore, the product design should result in primary stability which is higher than the typical required amount.
On the other hand, microroughness of the surface improves the osseointegration rate. Thus, the severity of the hazardous situation is controlled to increase the relevant primary and secondary stability.
Based on the above results of Fig. 1, pre-mitigation and post-mitigation overall accumulated risk values, there is a relatively acceptable advancement on compensating the risks. All the identified risks factors are mitigated and moved to the acceptable and conditionally acceptable range. Figure 2, is showing the difference on the RPN number before and after appropriate mitigations.

Conclusion
Through a complete risk management activity composed from risk analysis, risk evaluation, risk control, residual risk evaluation and production and post-production information this study has been performed. To complete the risk analysis, first of all, the identifiable risk factors (all the considered risk factors are directly or indirectly related to the final product quality) are gathered and listed. The risk value of each factor is then evaluated based on the severity and the frequency of occurrence on three categories, which are pictorially illustrated on Fig. 3.
The results of the residual risk factors after applying appropriate measurement are provided in Fig. 1 and Fig. 2. Different types of risks of the failure of the products, and also the procedures are included in this study. After applying the mitigations the residual risk of all the factors moved to the acceptable range or conditional acceptance range. At the end there is no risk on the non-acceptance region.

Materials and Methods
Based on the available standards for the risk classification of the medical devices, any risk at the application of the medical devices would be acceptable, conditionally acceptable or unacceptable. As defined in Fig. 1, there are 5 levels of severity including negligible, minor, serious, critical, and catastrophic which are rated from 1 to 5 based on their intensity [3]. In addition, the probability of occurrence of a hazardous situation has been classified. It is basically a continuous parameter, but in this case has dissected into 5 different levels including frequent, probable, occasional, remote, and improbable rated downward from 5 to 1. The RPN factor is then calculated from the product of severity and probability as the accumulated risk factor.
After estimating the accumulated risk factors, risk versus benefit analysis is necessary. While dental implants restore the function of tooth's root or in some cases restore its anatomy [1], the benefits should outweigh the risks. In Table 1, the green blocks represent the risks areas with acceptable benefits. The yellow blocks represent the conditional acceptance of the product, where there should be adequate warnings supplied for the users from the manufacturer. The specific terms of use have to be clearly emphasized in the instructions for use to prevent foreseeable misuse.
In order to start the analysis, at the evaluation stage, all the risk factors with their foreseeable sequence of events and their severity level from the design stage to the long term application are assessed and listed. Through the assessment, the hazardous situations are evaluated and the harms are predicted.
After that the primary (proposed) solution to alleviate the concern (altering the risk)

Declarations
Ethics approval: Not Applicable.

Consent for publication:
The authors are ready to sign any consent form or provide consent to publish sheet by their own format.
Availability of data and materials: Data and material are available upon request.

Competing interests:
The authors declare that they have no significant competing financial or personal interests that might have influenced the performance of the worked described here. The RPN graph before and after applying mitigations. The figure shows the criteria for the accumulated risk factor. Three colors of green, yellow a Figure 4 General structure of the risk management activity.