TX Q&A

Companion diagnostic reagents for tumor gene mutation detection using high-throughput sequencing technology (NGS) in human formalin-fixed paraffin-embedded (FFPE) tissue samples typically include multiple variant genes and sites in their detection range, based on methodological characteristics and specific indications. These variant genes and sites can be divided into two categories: 1. Primary sites are genes and sites with clear companion diagnostic significance, for which clinical evidence for companion diagnostics should be provided according to relevant guidelines. 2. Secondary sites currently lack clear companion diagnostic significance, but authoritative guidelines both in China and abroad have explicitly stated their clinical significance for corresponding indications. Clinicians can apply these genes and sites based on diagnostic guidelines and the patient's specific condition to guide the patient's treatment process. Furthermore, for multi-gene tumor detection products being developed in tandem with anti-tumor drugs, their detection range includes one or more variant genes and sites involved in clinical trials of the anti-tumor drugs. If current research results demonstrate potential clinical significance for companion diagnostics, the corresponding genes and sites in the product can be included as secondary sites in the application. Once the anti-tumor drugs are launched, these can be updated to primary sites with clear companion diagnostic clinical significance through a change process. Apart from the aforementioned sites, it is not recommended to include other variant genes and sites without clear clinical significance in the detection range of the reagent kit. Additionally, for tumor gene mutation detection reagents that test cell-free DNA in plasma and other samples, the clinical significance of each gene and site for blood-based companion diagnostics and other applications should be demonstrated.

It is recommended to detail the product's structural design in conjunction with the clinical requirements for the strength, toughness, and clamping stability of the closure clips. This should include the inner surface structure of the upper and lower arms, the dimensional parameters, connection structure, and locks. Please explain the basis for determining the structure and compare it with similar products already on the market.

Enhance-colored contact lenses (decorative colored contact lenses) are required to undergo fade testing. However, visibility-tinted contact lenses do not need to undergo fade testing. This includes soft contact lenses with visibility tinting and hard contact lenses that are colored to distinguish between left and right lenses.

The biological evaluation of the product should comply with the specific requirements of GB/T 16886.1 regarding relevant uses, application sites, and contact duration. The contact duration refers to the maximum cumulative time the product is in contact with the human body. Generally, the biological evaluation items should include: pyrogenicity, cytotoxicity, sensitization, irritation or intracutaneous reactivity, acute systemic toxicity, and hemocompatibility.

According to the requirements of standard GB/T 16886.1-2022 Table A.1, all medical devices, except those that come into contact with intact skin and mucous membranes, need to be evaluated for material-induced pyrogenicity. The material-induced pyrogenicity evaluation data can be submitted in the following ways: comparison and analysis with previous products to demonstrate the biological risk equivalence of the product submitted for approval; providing chemical characterization, toxicological risk assessment data of raw materials and final products to prove the product does not contain known pyrogenic substances (as listed in GB/T 16886.11 Appendix G), thus exempting it from pyrogen testing; if during evaluation it is found that the product contains substances that have known pyrogenic reactions and/or new chemical components or substances with unknown pyrogen potential, further evaluation of the pyrogenicity of these components or substances is required, or a pyrogen test on the final product should be conducted.

For the extractable performance study of contact lens products, finished lenses should be chosen for the extraction tests. The samples need to be representative; for example, for enhanced colored lenses, you can consider the type of dye and the total amount of the formulation. Considering the worst-case scenario, generally, lenses with the maximum total dye formulation that covers all types of dyes should be selected. If the lenses with the maximum total dye formulation do not cover all dye types, additional lenses that cover the remaining dye types should be included and subjected to separate extraction tests for validation.

For joint prosthesis products with hydroxyapatite/metal composite coatings, you should typically submit research data on the composition of the hydroxyapatite/metal materials, the surface morphology of the composite coating (thickness, porosity, average pore diameter), and the mechanical properties of the composite coating (shear fatigue, shear strength, tensile strength, and wear properties). When studying the mechanical performance of the composite coating, it's suggested to clearly identify the failure modes for each test (e.g., whether the failure occurs between the coating and the substrate, or between layers of the coating). Since there are no standard test methods, you should provide the rationale for the chosen test methods, parameters, and equipment design. For the test results, ample supporting data should be provided to prove their clinical acceptability. For such composite coatings, the performance indicators detailed in the product's technical requirements should specify the bonding strength, tensile strength, surface quality, surface roughness, and thickness of the coating.

The mandatory industry standard GB 8368-2018 for disposable infusion sets states: "The venting device must have an air filter to prevent microorganisms from entering the container it is inserted into." However, the standard does not provide specific test methods for this performance indicator. It is recommended that when submitting a registration application for disposable infusion sets, you refer to the YY/T 1551 series standards and provide research data that demonstrates compliance with bacterial retention performance and integrity tests.

It is recommended to select solvents according to Table 2 of GB/T 11417.7 "Test Methods for Physical and Chemical Properties of Contact Lenses." You should choose different types of solvents, including mild extraction solvent (e.g., distilled water), mildly extracting solvent (e.g., n-hexane), and strong extracting solvent (e.g., ethanol, etc.). If the recommended solvents in Table 2 are not applicable, you need to provide a study and justification for their inapplicability. In the application documents, you must provide the basis and validation data for the choice of solvents, demonstrating the suitability of the selected solvents. The validation should confirm that the chosen solvents are appropriate for the extraction performance study of the contact lens products.

First, you need to determine whether the remaining accessories can be considered as the same registration unit after deleting the main unit, according to the "Guiding Principles for the Division of Medical Device Registration Units." If feasible, you can apply for a change in registration to delete the main unit and keep the accessories while maintaining the original compatibility relationship. You will also need to modify the product name to match the accessories' name, and adjust the product's scope to clearly state that it is intended for use with the original main unit models. The product technical requirements should retain all relevant content to the accessories, as well as any performance indicators related to their use with the main unit.