Explanation of the time limit for registration application after the notification of innovative review results
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.
Can ordinary absorbable sutures and barbed absorbable sutures made of the same material be declared within a single registration unit? Do both types of sutures need separate biocompatibility evaluations?
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.
What issues should be considered when submitting a clinical trial database for in vitro diagnostic reagents?
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.
How should the inclusion and exclusion criteria for subjects be established in the design of clinical trials for in vitro diagnostic reagents?
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.
What factors should be considered in the coverage of gene mutation sites when developing non-originator companion diagnostic reagents for anti-cancer drugs?
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.
What are the key points of attention for the product instructions in the clinical trials of in vitro diagnostic reagents?
During the design and execution of clinical trials for in vitro diagnostic reagents, special attention should be paid to the consistency between the operational details of the clinical trial and the corresponding product instructions. This applies to the trial in vitro diagnostic reagents as well as comparison reagents and review reagents. Key contents of the instructions that should be focused on during clinical trials include the intended use, applicable sample types, sample anticoagulants, sample storage and handling requirements, sample processing reagents (such as nucleic acid extraction reagents) and other supporting reagents, applicable instrument models, test methods, result interpretation standards, limitations, etc. During the clinical trial design process, detailed standard operating procedures should be developed based on the instructions provided, ensuring that the clinical trial execution strictly follows these guidelines. The clinical trial testing process and results should support the claims made in the product instructions of the proposed product.
Can the positive judgment value/reference range be adjusted during the clinical trials of in vitro diagnostic reagents?
The positive judgment value/reference range for in vitro diagnostic reagents should be established and validated before the clinical trial. During the clinical trial, the interpretation of test results should be based on these fully validated positive judgment values/reference ranges. If, based on clinical reference standards, it is considered during the clinical trial that the set positive judgment value/reference range of the trial in vitro diagnostic reagent is unreasonable and needs adjustment, the data after adjustment cannot be used as clinical research data to confirm the clinical performance of the product. Instead, it can be used as research data for the positive judgment value/reference range. After adjustment, it is necessary to re-enroll clinical cases and conduct the clinical trial again.
Do products listed in the trial approval catalog have to conduct clinical trials domestically?
According to the "Technical Guidance on Accepting Foreign Clinical Trial Data for Medical Devices," medical devices listed in the "Catalogue of Class III Medical Devices Requiring Clinical Trial Approval" may submit foreign clinical trial data in accordance with this guidance. If the foreign clinical trial data meets the technical requirements for registration in China and the data is scientifically robust, complete, and sufficient, it is not necessary to conduct clinical trials domestically.
How to accept foreign clinical trial data
Foreign clinical trial data refers to research data generated during the process of confirming the safety and efficacy under normal usage conditions of medical devices intended for registration in China, conducted entirely or simultaneously at clinical trial institutions abroad that meet the requirements of the host country. According to the "Technical Guidance on Accepting Foreign Clinical Trial Data for Medical Devices," foreign clinical trials should adhere to ethical, legal, and scientific principles. When accepting foreign clinical trial data, it is important to analyze and evaluate the impact of differences in technical review requirements, subject populations, and clinical trial conditions on the results. If the foreign trial data meets the relevant registration requirements in China and is scientifically robust, complete, and sufficient, it can be accepted.
When using a parallel control design in clinical trials, how should the control device be selected?
For therapeutic products, when choosing a positive control, priority should be given to clinically recognized, marketed products of the same type that have proven efficacy and safety. If it is not feasible to use a marketed product of the same type for valid reasons, a product that is as similar as possible can be used as a positive control. Alternatively, standard treatment methods may be considered. Standard treatment methods include various scenarios, such as drug therapy. If there are no similar marketed products or standard treatment methods available for the trial device, and if the efficacy of the trial device might include a placebo effect, the trial design should consider a placebo control, taking into account ethical considerations at this stage. If the efficacy of a marketed product has not been clinically recognized, the trial design can consider standard treatment methods or placebo controls depending on the specific circumstances. The applicant must thoroughly justify the reasons for choosing the control.