Can samples be reused multiple times during the analytical performance evaluation process of in vitro diagnostic reagents?
The analytical performance of in vitro diagnostic reagents includes accuracy, precision, detection limit, specificity, and other aspects. It requires the inclusion of samples from different sources, types, concentrations, and other characteristics to fully evaluate the product's performance. Therefore, the reuse of samples should be avoided as much as possible during the evaluation process of these analytical performances.
When national standards or reference materials are updated, what kind of product inspection report is required for the continued registration of in vitro diagnostic reagents?
According to the management by the National Institutes for Food and Drug Control (NIFDC) of national standards and reference materials for in vitro diagnostic reagents, the batch number of these materials is composed of a "product code (6 digits) + batch number (6 digits)" and is publicly available on the NIFDC official website for inquiry. Updates to national standards and reference materials include two scenarios: "batch replacement" and "generation change." The difference is that "batch replacement" involves the preparation of a new batch to ensure the supply of national standards and reference materials without any change in their setup, value, performance acceptance criteria, or product code—only the batch number changes. A "generation change," however, indicates a comprehensive change in the national standards or reference materials, possibly altering their setup, value, or performance acceptance criteria, with both product code and batch number changing. If an in vitro diagnostic reagent product had previously submitted an inspection report meeting the requirements of the national standards or reference materials and was approved, and if there is a "generation change" update to these standards or materials, the registrant must provide a new inspection report demonstrating compliance with the updated national standards or reference materials at the next renewal of registration. If there is only a "batch replacement" update, the registrant does not need to submit a new inspection report for compliance with the post-update national standards or reference materials at the next renewal, but must describe in the registration documentation how the product continues to meet the requirements of the national standards or reference materials.
What should be considered in the heat treatment process for laser selective melting metal materials used in additive manufacturing for dental restoration?
It is necessary to first clarify the heat treatment methods and parameters for the product, and to evaluate and verify the suitability of these heat treatment methods. It is also important to establish the basis for determining heat treatment parameters (including heating time, holding temperature, and holding time) and the criteria for the acceptability of the results after heat treatment.
The product's nominal operating voltage is 100-230V, but industry standards specify that "the device should work normally within an AC voltage range of 220V±22V." How should testing be conducted?
First, it's important to clarify that the starting point for the mentioned standard clause is to ensure that the product can still function normally in China despite potential voltage fluctuations. Secondly, the product's stated voltage range is merely the claimed supported rated voltage, which is not the same issue as the one described before, and there is no contradiction between them. Therefore, for the situation described in the question, the product should be registered according to its actual design. The stated voltage range should be based on the actual design parameters of 100-230V, and testing should still be conducted within the standard's required range of 220V±22V.
Principles for Choosing Between Quantitative and Qualitative Cytotoxicity Evaluations and the Recommended Order of Preference
Quantitative evaluation of cytotoxicity can objectively measure parameters such as cell count, total protein, enzyme release, release of vital dyes, reduction of vital dyes, or other measurable parameters. It is less susceptible to subjective biases of the tester, offers relatively high sensitivity, and provides clear determination limits. Currently, the MTT assay is a widely used method in China for quantitative cytotoxicity testing. In contrast, qualitative evaluations of cytotoxicity involve more subjectivity from the evaluator and are more suitable for screening purposes. Additionally, there are instances in practical testing where the results of qualitative and quantitative evaluations do not align (e.g., when the extract of the test sample causes significant changes in the absorbance of the culture medium). Therefore, it is currently recommended to primarily use quantitative evaluation methods, supplemented by qualitative evaluations when necessary.
When can clinical trial comparative method testing be outsourced to third-party institutions/laboratories?
In clinical trials for in vitro diagnostic reagents, all testing should, in principle, be completed by the institution conducting the clinical trial. However, if the comparative methods involve laboratory testing reference methods that are not standard clinical techniques and require specialized equipment and conditions—conditions that most clinical trial institutions do not have—then institutions lacking these capabilities can delegate these specific tests to specialized laboratories that have the necessary qualifications. The clinical trial institution should then validate the test results. Examples of such cases include nucleic acid sequencing and GC-MS/MS tests. However, if the comparative methods are routine clinical tests, such as standard pathogen isolation and culture or broth microdilution method (used for in vitro antibiotic susceptibility tests), despite their complexity and the need for specialized laboratory conditions and techniques, they should still be conducted by the clinical institution and not outsourced to third-party labs. To ensure the quality and control of the clinical trial, it is important to select capable clinical institutions to conduct the trials, standardize procedures strictly during the trial, and evaluate consistency across different institutions and operators.
For orthopedic and dental implant devices, when changing the registration to add a sterilization method, which tests need to be conducted.
When changing the registration through a permit item to add a sterilization method, it is necessary to submit corresponding sterilization validation documents and conduct sterility performance testing. If the addition of a sterilization method leads to changes in other performances, testing for these should also be conducted. For example, if ethylene oxide sterilization is added, additional tests for sterility and ethylene oxide residue must be included.
Implantable Cardiac Defibrillators and Similar Products Regarding the Reference to GB 16174.2-2015
For implantable cardiac defibrillators and similar products that have already referenced the GB 16174.1 and YY 0989.6 standards in their technical requirements, although implantable cardiac defibrillators have pacing functions, there is no need to reference the GB 16174.2 standard. This is because the YY 0989.6 standard has already sufficiently considered the pacing function of implantable cardiac defibrillators and has made corresponding provisions.
How to choose a clinical evaluation pathway for registering a hip joint prosthesis product? What should be considered if choosing a clinical evaluation pathway for the same kind of product?
When applying for the registration of a hip joint prosthesis product, you should select the appropriate clinical evaluation pathway based on the specific intended use and technical characteristics of the product. Generally, if there are products of the same kind with similar intended uses and technical features (such as mechanism of action, materials, design, product performance, etc.) already on the market domestically, the registrant may consider conducting a clinical evaluation through the same kind pathway. When conducting a clinical evaluation for a hip joint prosthesis of the same kind, it must comply with the applicable parts of the "Technical Guidelines for Clinical Evaluation of Medical Devices." The following aspects should be considered: 1. Selection of the same kind product: Choose a product that is already on the market domestically and has the same intended use and as similar as possible technical characteristics to the product being registered. If the selected same kind product significantly differs from the product being registered, more scientific evidence must be provided to prove that these differences do not adversely affect the safety and effectiveness of the product. Applicants are encouraged to conduct comprehensive research on similar products that are already on the market. 2. Comparison between the declared product and the same kind product: Clearly define and detail the similarities and differences in the intended use and technical characteristics between the declared product and the same kind product. 3. Provision of clinical data for the same kind product: The applicant needs to clarify the relevance of the clinical data to the same kind product. It is recommended that applicants extract key elements from the clinical literature to facilitate subsequent data analysis. 4. Provision of scientific evidence for differences: Appropriate scientific evidence must be submitted based on the specific differences between the declared product and the same kind product, including non-clinical study data and/or clinical data that can represent the declared product.
How to determine the residual limits of ethylene oxide (EO)
Applicants can refer to relevant standards for the residual limits of ethylene oxide (EO) per item/set of medical devices. If referring to the allowable limits in GB/T 16886.7-2015, applicants should consider the use of multiple devices in conjunction during actual product use and combine this with the actual control level of EO residues in the product. They should establish EO residual limits for individual/set products that meet the requirements and provide relevant justification.