TX Q&A

Pyrogenic reactions are among the most severe adverse reactions when using infusion products clinically. Pyrogens include bacterial pyrogens, endogenous high-molecular pyrogens, endogenous low-molecular pyrogens, and chemical pyrogens, with endotoxin tests targeting bacterial endotoxins produced by Gram-negative bacteria. 1) Pyrogens cannot be eliminated by sterilization methods; 2) Other pyrogenic substances besides endotoxins can also cause pyrogenic reactions. Therefore, the potential risk of pyrogenic reactions cannot be solely determined by testing the limits of endotoxins. It requires reducing this risk through manufacturing processes and process controls.

Currently, it is recommended that the primary research endpoints for clinical trials of peripheral drug-coated balloon catheters include both primary efficacy endpoints and primary safety endpoints. For primary efficacy endpoints, a composite endpoint is recommended, which includes the rate of clinically driven target lesion revascularization and the rate of restenosis diagnosed by Doppler ultrasound at 12 months post-operation. Similarly, for primary safety endpoints, a composite endpoint is recommended, including all-cause mortality at 30 days, as well as the amputation rate of the lesion limb and the rate of clinically driven target vessel revascularization (TVR) at 12 months post-operation.

The content within the same registration certificate should meet the requirements of the "Guidelines for the Division of Medical Device Registration Units." Whether it's possible to add new models or accessories to the original registered product depends on the differences between the new and existing models, and the relevance of the new accessories to the original product. If the new models or accessories can be classified into the same registration unit as the already registered product according to the "Guidelines for the Division of Medical Device Registration Units," then it's possible to apply for an addition through a change in the license items.

A ventilator is a type of lung ventilation device used to automatically increase or provide ventilation to the patient's lungs. According to the "Guidelines for the Division of Medical Device Registration Units," active medical devices based on different technical principles should, in principle, be classified into different registration units. Given the current level of technology, products such as therapeutic ventilators, home care ventilators, emergency and transport ventilators, high-frequency jet ventilators, and high-frequency oscillatory ventilators, which are based on different technical principles, should be classified into different registration units. For therapeutic ventilators that use different technical principles, such as pneumatically controlled ventilators and electrically controlled ventilators, they should be classified into different registration units. Ventilators that have the same technical principle but different product design structures (for example, ventilators with different airway designs) should, in principle, be classified into different registration units. Passive consumables used in conjunction with ventilators (such as breathing circuits, tracheal tubes, masks, etc.) should, in principle, be classified into different registration units from the ventilators.

For some in vitro diagnostic reagents that currently lack a clear clinical diagnostic "gold standard" and have no comparable similar products on the market, clinical trial researchers should establish reasonable methods for comparative studies based on existing clinical practices and theoretical foundations. In some cases, where nucleic acid sequence determination, GC-MS/MS, and other laboratory reference methods are used as comparison methods in clinical trials of certain in vitro diagnostic reagents, these methods are not routine clinical testing techniques and require specialized equipment and testing conditions, which clinical trial facilities may not possess. In such situations, applicants should choose clinical trial facilities with the necessary conditions to conduct the trials whenever possible. If some clinical trial facilities lack the testing conditions, they can outsource this testing to specialized sequencing institutions or laboratories with specific testing qualifications, and the results of the testing should be acknowledged. Applicants should submit documents proving the delegation between the clinical trial facility and the commissioned institution, and assess the methodological research and overall quality of the comparative methods. Testing should not be delegated to the applicant's own laboratory.

Zirconia ceramic blocks are generally made of zirconia, yttria, hafnia, alumina, and other oxides. They are used in the production of crowns, bridges, inlays, veneers, and other restorations for fixed dental prostheses. Products with different main components should be divided into different registration units; products with different key performance characteristics such as flexural strength, sintering density, shrinkage/expansion rate, and translucency due to different compositions should be divided into different registration units; products produced using different forming processes should be divided into different registration units, for example, zirconia blocks produced using the "slip casting" process and the "dry pressing" process should be considered separate registration units. Zirconia ceramic blocks with the same composition and process but different shapes or sizes can be declared as a single registration unit.

For comprehensive registration testing, select products that include all raw materials and components, have the most complex structure, pose the highest risks, and have performance characteristics that can cover other models within the same registration unit. For products within the same registration unit, it is recommended to conduct comprehensive testing on the largest capacity adsorber model, while also testing the physical performance of the smallest capacity adsorber model.

It is recommended that such products prioritize terminal sterilization methods. If terminal sterilization is truly not feasible for the product, consideration can be given to aseptic processing methods such as filtration for sterilization control. However, documentation should be provided to prove the rationale for choosing aseptic processing for such products. Additionally, the applicant must describe the quality assurance system and sterilization methods used to ensure product sterility and provide corresponding verification data.

Dental handpieces, spray guns, and other oral devices used in clinical settings involve parts like the handpiece and nozzle coming into contact with oral tissues during operations, necessitating a biocompatibility assessment. Applicants should describe the materials in contact with oral tissues, as well as the nature and duration of contact during use. Referring to the "Notice on Issuing the Guidelines for Biological Evaluation and Review of Medical Devices" (National Food and Drug Administration [2007] No. 345), if a company submits a declaration stating that no reevaluation as stipulated in Article 4(1) of Appendix 1 has occurred, a biological evaluation does not need to be conducted again. Otherwise, the biocompatibility assessment should be carried out in accordance with the requirements of National Food and Drug Administration [2007] No. 345, GB/T 16886.1 "Biological Evaluation of Medical Devices Part 1: Evaluation and Testing in Risk Management Processes," or YY/T0268 "Biological Evaluation of Dental and Oral Medical Devices Part 1: Evaluation and Testing."

The association of EMC testing reports is to ensure the consistency between the safety testing reports and the test samples used in the EMC testing reports. After product registration approval, the registrant should organize production in accordance with the approved content to ensure that the product remains unchanged. Therefore, there is no need for association during renewal registration. During the validity period of the registration certificate, if there are corrective actions that do not involve licensed changes to the product, the registrant should conduct relevant verification and confirmation work in accordance with the requirements of the quality management system to ensure that the corrective actions do not affect the safety and effectiveness of the product. When applying for renewal registration, it should be stated in the "Declaration of No Changes in Products for Renewal Registration" that "changes to the product are controlled through the quality management system, and there are no changes to the items listed on the registration certificate."