TX Q&A

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.

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.

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 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.

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.

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.

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.

The endoscopes listed in the exemption from clinical trials catalog are limited to products with conventional designs. Disposable electronic endoscopes (including those designed for single use entirely, or combination endoscopes with only the insert part intended for single use), 3D endoscopes, and capsule endoscopes do not fall under the products exempt from clinical trials.

To meet the needs of epidemic prevention and control, companies should continuously monitor virus mutations and proactively evaluate the detection of new coronavirus variant strains for all nucleic acid detection reagents. The evaluation results should be submitted along with the registration materials (including product registration, change of registration, and renewal of registration). For products that have been issued but not yet updated, companies should also supplement this information. The evaluation should involve bioinformatics analysis based on the gene loci, primers, and probe designs used in the product, as well as the virus mutation patterns. If a variant strain is found that may affect product detection, further validation experiments should be conducted using real clinical variant strains containing the relevant mutation sequences or synthetically created samples. When using synthetic samples for validation experiments, dilution studies should be conducted for all applicable sample types of the product, covering at least the minimum detection limit and precision. For the methods of study, refer to the "Key Points for Technical Review of Registration of 2019 Novel Coronavirus Nucleic Acid Detection Reagents." If the evaluation indicates that the reagent may miss detecting variant strains, it is recommended to modify the product design and re-evaluate the product.

Clinical trial data for in vitro diagnostic reagents should include the clinical trial protocol to be implemented and the corresponding written opinion from the ethics committee consenting to the conduct of the clinical trial. Due to possible changes in the clinical trial protocol, multiple versions may exist, and the following principles should be noted when submitting application materials: If changes to the clinical trial protocol occur before the official start of the trial, the final version of the clinical trial protocol to be implemented should be submitted, along with the ethics committee's written opinion corresponding to that version. If the clinical trial has already started and changes to the protocol occur during the process, both the pre- and post-change versions of the clinical trial protocol and their ethical documents should be submitted together, with a clear explanation of the reasons for the changes and their impact on the ongoing clinical trial. It is important to thoroughly research the scientific validity, rationality, feasibility, and compliance of the protocol before the clinical trial, to develop and strictly implement the plan; changes to the protocol should not be made arbitrarily during the clinical trial unless necessary.