TX Q&A

According to the "Guidelines for the Preparation of Technical Requirements for Medical Devices" (National Medical Products Administration Notice No. 8 of 2022) under "Section IV: Performance Indicator Requirements," the "shelf life of medical devices" is considered "research and evaluative content that is not recommended to be specified in the performance indicators of technical requirements." This recommendation also applies to the technical requirements for in vitro diagnostic reagents, meaning "stability" does not need to be included as a performance indicator in the technical requirements for these products.

For passive vascular implantable medical devices that include a delivery system or accessories, such as stents and occluders preloaded onto a delivery system, it is advisable to conduct separate biological evaluations for the components intended to remain in the body long-term and for the delivery system or accessories during the registration process. This is because there is a significant difference in the nature and/or duration of contact with the body between the parts expected to be permanently implanted and their delivery systems or accessories.

1. The testing method for the peak tensile strength of intravascular catheters should comply with YY0285.1-2017. However, due to different segmented structures of various products, the segments that need to be tested vary. To further clarify whether the tested body and connections meet the standard requirements, applicants should refine the testing methods based on the specific structure of the product, such as specifying the exact locations of each test segment and their minimum outer diameter. 2. For intravascular guidewire devices, the testing methods should be based on the YY0450.1-2020 standard, taking into account the requirements mentioned above. 3. It is recommended that components used in the delivery systems for intravascular devices also refer to the above requirements.

Dental implants are generally made of titanium or titanium alloys and are implanted into the upper and lower jawbones of edentulous areas through surgical procedures to provide fixation or support for restorations such as dentures, thereby restoring the patient's chewing function. To clarify the clinical evaluation requirements for implants of the same type, unify evaluation standards, and combine the current development status of the dental implant (system) industry and current technical review requirements, targeted proposals and standards for the clinical evaluation of such products were developed after researching the product review requirements in the United States, Japan, and the European Union. The Medical Device Technical Review Center organized the drafting of the "Guidelines for Clinical Evaluation Registration Review of Dental Implant Systems of the Same Type," and a draft for comments was released on November 23, 2021. The draft summarizes the current technical review requirements for the clinical evaluation of dental implants, clearly stating that applicants can conduct clinical evaluations of dental implant systems by comparing them with one or more medical devices of the same type. The comparison focuses on, but is not limited to, the product's scope of application, structural composition, raw materials, mechanical properties, surface treatment, etc. (mechanical properties, etc., can include measured data comparison of the declared product with the same type of product), proving their fundamental equivalence. Then, data obtained from clinical trials or clinical use of the same type of products (such as clinical literature data, clinical experience data, etc.) can be analyzed and evaluated to prove the safety and effectiveness of the declared product. Regarding differences between the declared product and products of the same type, supporting materials can be submitted showing that these differences do not adversely affect the safety and effectiveness of the declared product. For example, if there is a significant difference in surface modification between the declared product and products of the same type, animal experiments can be conducted to observe whether the surface modification adversely affects the bone integration and initial stability of the implant. Combining the intended clinical use of the declared product, the level of similar products on the market, clinical data of the declared product (if any), and clinical treatment requirements, a comprehensive analysis of the clinical acceptability of the declared product is performed to demonstrate its safety and effectiveness. Currently, several domestic dental implant companies have submitted clinical evaluation materials through the same type comparison clinical evaluation pathway and have obtained registration certificates.

Due to differences in product design, wound closure mechanisms, and performance indicators between ordinary absorbable sutures and barbed absorbable sutures, it is necessary to conduct separate product performance studies, research on changes in tensile strength over time in animal bodies, and clinical evaluations. It is recommended to file for registration as separate registration units. If the two types of sutures produced by the same company use the same raw materials and manufacturing processes (except for the cutting process), it is permissible to conduct a biocompatibility evaluation using just one type of the sutures.

If a part of a medical device's product composition is essential for achieving its intended use and basic functions, it cannot be registered as an "optional accessory." However, if the surgical instruments are intended to be optional, allowing for the selection of different models to achieve different functions, they can be registered as "optional accessories." Purchasing or not purchasing certain models of surgical instruments does not affect the overall safety and effectiveness of the product. Regardless of whether the surgical instruments are registered as "optional accessories," the requirements for technical review are the same and must be reflected in the product's structure and composition.

According to the requirements of the "Special Review Procedure for Innovative Medical Devices" (No. 83 of 2018), "If an innovative medical device has not been applied for registration within 5 years after the notification of the review results, it will no longer be reviewed under this procedure." Considering the impact of the COVID-19 pandemic and to encourage enterprises to resume work and production, for projects with sufficient evidence proving that the pandemic has caused delays in registration applications, the above time limit may be appropriately extended, up to a maximum of 2 years. If the registration application is still not accepted by then, the product will no longer be considered as an innovative medical device.

According to the requirements for submission of documentation, starting from January 1, 2022, all in vitro diagnostic reagents undergoing clinical evaluation through clinical trials must submit a clinical trial database. Applicants must strictly adhere to the "Guidelines for the Submission and Review of In Vitro Diagnostic Reagent Clinical Trial Data" when submitting the clinical trial database. The clinical trial database should include the original database, analysis database, explanatory documents, and program codes (if applicable). The original database refers to all cases and sample information enrolled in the clinical trial according to the protocol. The analysis database, which is formed from the original dataset for ease of statistical analysis, should include the corresponding cases and sample information used in the statistical analysis. Explanatory documents should at least include a data description document and a statistical analysis explanation document. If program codes are used in the management or statistical analysis of the database, these should be provided.

In the clinical trials of in vitro diagnostic reagents, the inclusion and exclusion criteria for subjects should be reasonably set based on the intended use of the product, including the applicable population and indications. It is important to ensure that the clinical trial subjects come from the population and indications claimed in the product's intended use, such as individuals with certain symptoms, signs, physiological or pathological states, or specific epidemiological backgrounds. Including subjects from non-target populations may introduce selection bias, leading to clinical trial results that do not accurately reflect the true performance of the product. For example, in vitro diagnostic reagents used for the auxiliary diagnosis of a certain disease should not arbitrarily include a large number of asymptomatic healthy subjects in clinical trials. Inappropriate inclusion criteria can lead to deviations in the evaluation of the product's clinical sensitivity and specificity from its true performance.

When developing companion diagnostic reagents for anti-cancer drugs, particularly those that are non-originator, it is crucial to consider the selection of genes and the coverage of mutation sites in the product design. If multiple mutation sites are known for the same gene for the same companion diagnostic purpose (e.g., the same companion drug), the extent of mutation site coverage should be thoroughly considered in subsequent product designs based on a product risk-benefit analysis. The range of mutation sites detected should not be arbitrarily reduced for the sake of ease of product evaluation. For example, when using KRAS gene mutations for tumor companion diagnostics, since it involves negative companion diagnostic gene testing and is related to adverse drug reactions, insufficient coverage of mutation sites may increase patient risk. Therefore, the product design should thoroughly reference the gene coverage in the original research product or clinical trials of the drug to ensure adequate and appropriate mutation coverage. This approach helps in minimizing risks and enhancing the therapeutic efficacy of the companion drug.