TX Q&A

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.

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.

In such cases, the original registered product can be chosen as the same type of product to complete the clinical evaluation. The comparison with the same type mainly focuses on whether there are differences between the declared product and the original registered product. If there are no differences, the clinical data that can be provided include both pre-market and post-market clinical data of the product, including clinical experience data such as post-market adverse events.

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.

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.

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.

The "Regulations on the Supervision and Management of Medical Devices" stipulate that clinical evaluations of medical devices can be conducted based on product characteristics, clinical risks, and existing clinical data. These evaluations can be carried out either through clinical trials or by analyzing and evaluating clinical literature and data of similar medical devices to demonstrate their safety and effectiveness. Applicants for registration may refer to the "Technical Guidance on Deciding Whether to Conduct Clinical Trials for Medical Devices" to determine the necessity of conducting clinical trials. Additionally, they should consider the recommended clinical evaluation pathways for products related to the sub-categories in the "Medical Device Classification Catalog" recently released by our center, to choose the appropriate clinical evaluation pathway.

When there is a change in the packaging specifications of in vitro diagnostic reagents, it is necessary to describe in detail the differences in packaging specifications before and after the change. Based on these differences, identify all relevant potential risks and analyze and verify these risk factors. For example, if there are differences in the form of reaction (such as drug detection products) or the size of the reaction strips (such as PCR amplification hybridization products) before and after the change, analytical performance evaluation data of the new packaging specifications should be submitted. If there is a significant change in the packaging capacity or container, leading to increased risks of evaporation or loss, consider whether there are changes in the product's shelf life, usage stability, and calibration frequency.

Interference tests are generally conducted using a paired comparison method, comparing the differences in results between samples containing high concentrations of interfering substances and those containing none or normal concentrations (control). For qualitative reagents that do not provide quantitative data, results of interference tests can be represented simply as positive or negative. However, it is important to include samples at weakly positive levels in the study. For qualitative reagents that make threshold judgments based on quantitative data (such as OD values, Ct values, or count results), it is recommended to perform a differential analysis of the quantitative data, rather than solely using positive or negative to represent the results of the interference tests.

To meet the needs of epidemic prevention and control, companies should continuously monitor virus mutations for all COVID-19 nucleic acid test kits, whether before or after they are marketed. Companies must actively assess the kits' ability to detect virus variants. If the product is in the pre-market stage, evaluation results should be submitted along with the registration materials. If the product is already on the market, companies need to cooperate with the working group assessing the detection capability of coronavirus variants and regularly submit evaluation data.