Non-active Device

The toxicity, allergic reaction and other adverse biological reactions of dental alloys to human bodies are closely related to metal elements released into the oral cavity. The degree of biological reaction of dental alloys is affected by the nature and concentration of elements released as well as the duration of exposure to oral tissues. It is recommended to consider the biocompatibility of dental noble-metal alloys from the following aspects:

1. The quantity, type, microstructure and composition of phases in alloy;
2. Whether there are such elements as copper, zinc, silver, calcium and nickel;
3. Single metal elements may be greater than alloyed metal elements;
4. Various combinations of alloy elements in the oral cavity may change the corrosion and biocompatibility of alloys;
5. Whether the element release level of alloy containing noble metal elements is lower than that of ordinary alloys.

 The consumables for in vitro assisted reproduction (except the fluid for in vitro assisted reproduction) act on gametes, zygotes, and embryonic cells at different developmental stages. Therefore, in addition to routine biological evaluations, in vitro mouse embryo assay should be performed with reference to YY/T 1434 for such products. Because the results of mouse embryo assay are an important indicator for evaluating the safety of such products, according to the industry requirements and requirements of clinical assisted reproduction for such products, mouse embryo assay should be used as a routine quality control item for such products.

The biological evaluation of product should consider the materials used in the manufacture of the product, intended additives, process contaminants and residues, leachable substances, degradation products, physical properties of the final product, the individual components and their interactions in the final product, packaging materials and the influence of the preservation medium on biocompatibility as well as other factors, so the biocompatibility test of the product should in principle be carried out on the final product, or on the representative samples taken from the final product. If it is not feasible to use the final product for testing, it may be considered to use the specimens produced with the same processes as the final product for testing, but the representatives of the specimens needs to be fully analyzed and demonstrated.

For an orthopedic implant made of pure titanium or titanium alloy material is treated with colored anodizing, if there are additional residual impurity elements in addition to the matrix element, biological evaluation should be performed in accordance with the "Notice on Issuing the Guidelines for Biological Evaluation and Review of Medical Devices” (CFDA [2007] No. 345) and GB/T 16886 series standards to analyze the source of surface impurity elements and the reason for the introduction thereof, fully demonstrate the biological risk of the product, and meanwhile clarify the corresponding quality control measures of impurity elements in colored anodizing process.

Dressing products often need replacement during clinical use, and the product itself has a certain fluid absorption nature. Therefore, the following issues need to be addressed in biocompatibility evaluation:

1. When preparing the extract of dressing products, the determination of the extraction time should take into account the cumulative clinical use time of the product; when determining the volume of the extraction medium, in addition to considering the extraction ratio, the volume of the extraction medium to be absorbed by the product should also be considered.
2. For the evaluation items, the cumulative contact duration between the product and the human body should be considered, not the single contact duration.

For the abutment products which have undergone colored anodizing, it is necessary to perform biological evaluation according to the "Notice on Issuing the Guidelines for Biological Evaluation and Review of Medical Devices" (CFDA [2007] No. 345), GB/T 16886 and YY/T 0268 series standards and to perform analysis on the surface elements of product; if any impurity element other than matrix element is contained, it is necessary to analyze the source of surface impurity element and the reason for the introduction thereof, conduct full demonstration on biological risks of the product caused, and clarify the corresponding quality control process and risk prevention and control measures for colored anodizing.

For the evaluation indicators with statistical differences in the subchronic toxicity test, the test report should clarify whether the relevant differences impact on biological evaluation results and explain the reasons, analyze and determine the relationship between the relevant differences and the tested product, instead of simply listing items with statistical differences. The administrative counterpart should analyze and evaluate the abnormalities or risks indicated in the test report. In addition, it is necessary to provide the basis for the determination of the test dose and consider the safety factor for extrapolation of the dose to human beings.

Real-time stability verification data should be submitted for all models and specifications of dialysate concentrates. The verification should consider the characteristics of the product to examine the impact of the expected conditions, temperature, humidity, time and other factors of storage, transportation and packaging on the product.

It is recommended to refer to the requirements for long-time testing of pharmaceutical products in “Guidelines for the Stability Test of Drug Substances and Products” in "Pharmacopoeia of the People's Republic of China" to submit the stability verification data of concentrates and determine the shelf life of the product based on the results.

In the process of stability verification, it is necessary to observe the products of all models and packing volumes. According to the actual situation of the product, determine the appropriate conditions of the storage, transportation and packaging, and the storage condition of temperature and humidity in the south or north expected, check for the stability of the concentrate at different assessment time points.

The observation items should include all performance in technical requirements and analysis of chemical contaminants. It is also necessary to provide the test results of such items as solute concentration, insoluble particles, microbial limit (or sterility), and endotoxin of the concentrates at different assessment time points in accordance with the technical requirements. For dry powder, the comparison result of dissolution time should be added. For the dry powder B products for online use, the test results of ion concentration and pH at four time points at least (at the beginning of dialysis, the two

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For verification of radiation sterilization verification of non­active implant, it is necessary to define the radiation source and radiation dose, provide the corresponding basis for such determination, as well as the initial average bioburden test report and dose verification test report, and provide the sterility test report of product after sterilization with minimum radiation dose determined based on the initial average bioburden. The radiation sterilization validation report should include the selection of the product and packaging materials, the determination of the product loading mode, and the product dose map, etc. It should be noted that the establishment of radiation dose for sterilization should not be based on biological indicators (generally bacillus pumilus spores), but should be based on microorganisms (e.g. bacillus stearothermophilus spores) that have stronger radiation resistance loaded in sterilization articles. If the product used for sterilization verification is not the product under application, it is necessary to provide the supporting data demonstrating its equivalence to the product under application in terms of raw materials, sterilization methods, sterilization doses, packaging materials, packaging processes, packaging methods, and other factors that affect resistance to bacteria.

The sterilization method can be added or changed through the procedures for change of permission items. In case of any change in the sterilization method of animal-derived dental biomaterials, it is necessary to submit at least the sterilization effectiveness verification report and the product shelf life verification report, and to confirm whether the change in sterilization method has any influence on the safety and effectiveness of the product. If the product performance is affected by sterilization, it should be re-verified. If the sterilization process is used as the process of virus inactivation, the change in sterilization method requires re-verification of virus inactivation; if the sterilization process is not used as the process of virus inactivation, it is not necessary to re-verify virus inactivation.