Under what circumstances can a third-party institution / laboratory be entrusted with the testing of comparative methods in clinical trials
In the clinical trials of in vitro diagnostic reagents, all tests shall be completed by the institution undertaking the clinical trials. However, a third-party testing institution may be entrusted if all the following conditions are met:
The reference methods for laboratory testing are adopted for the comparison methods,These methods are not routine clinical testing technologies,Require special equipment, instruments and test conditions, andClinical trial institution do not have relevant testing conditions
The test results of the third party shall be recognized by the clinical trial institution. For example,tests for nucleic acid sequencing and GC-MS / MS test could meet the above conditions. However, if the comparison method is a routine clinical test method, such as general pathogen isolation and culture, micro broth dilution method (for in vitro antibiotic susceptibility test), although the test operation is complex and requires special laboratory conditions and testing technology, the test should still be completed by the clinical institution instead of a third-party laboratory. In order to ensure the quality of clinical trials, clinical institutions capable of undertaking relevant trials should be selected to carry out clinical trials. In the process of clinical trials, relevant trials should be strictly standardized, and the consistency evaluation between institutions and operators should be carried out.
What tests are needed for orthopedic and oral implant devices to add sterilization methods in a registration of change?
If a manufacturer intends to add more sterilization methods in a change of permission items, the corresponding sterilization verification data and test the sterility performance should be submitted. Any other performance changes caused by the addition of sterilization methods should be tested. For example, if ethylene oxide sterilization method is newly added, sterility test and ethylene oxide residue test must be added.
How to determine the index of ethylene oxide (EO) residue limit?
The applicant may refer to the EO residual limit index for a single piece / set of devices in relevant standards. If reference is made to the allowable limit in GB / T 16886.7-2015, the applicant shall consider the combined use of multiple devices during the actual use of the product, and formulate the ethylene oxide residue limit for a single product / set in combination with the actual control level of EO residue of the product, and provide relevant basis.
When the overseas applicant carries out clinical evaluation through the clinical trial path, if the overseas clinical trial data is provided, is it still necessary to carry out clinical trials in China?
Article 5 of the Technical Guiding Principles for Accepting Overseas Clinical Trials of Medical Devices has made it clear that “if relevant requirements for clinical trials are specified in technical review guidelines for specific medical devices, such requirements shall be considered for the overseas clinical trials. When there is inconsistency, sufficient and reasonable evidence and basis shall be provided”. Therefore, if the applicant has submitted clinical trial data conforming to ethical, legal and scientific principles in accordance with this Technical Guiding Principle, and fully considered the differences in technical review requirements, test population and clinical trial conditions, it is not necessary to carry out additional clinical trials in China.
Is it necessary to carry out virus inactivation verification in a qualified laboratory for medical devices of animal origin?
Risks vary in different animal sources, production processes and applicable products. For some common virus inactivation processes, such as organic matter, radiation, strong acid, etc., the processes and methods are relatively mature which have many references. Therefore, it is not necessary to carry out laboratory verification one by one. Instead, it can be considered to refer to biological evaluation, immune prototype evaluation, clinical evaluation and other methods, and replace them with literature and historical data. Regarding qualification, there are no relevant provisions in the current medical device regulations.
Are disposable electronic endoscopes, three-dimensional endoscopes and capsule endoscopes included in clinical trial exemption list?
The endoscopes mentioned in the clinical trial exemption list are limited to conventional-designed products. Endoscopes like disposable electronic endoscopes (including combined endoscopes that are disposable as a whole and only the insertion part is disposable), three-dimensional endoscopes and capsule endoscopes are not included in the clinical trial exemption list.
What should be noted when submitting the ethical documents and clinical trial protocols for in vitro diagnostic reagents?
In the clinical trial dossiers of in vitro diagnostic reagents, the implementation plan of the clinical trial and the corresponding written comments of the ethics committee agreeing to carry out the clinical trial shall be submitted. Due to the change of clinical trial protocol, there may be multiple versions. The following principles should be noted when submitting application dossiers:
If the the clinical trial protocol changes before the formal implementation of the clinical trial, the clinical trial protocol of the final version shall be submitted, together with the written comments of the ethics committee corresponding to the version.If the clinical trial has started and the protocol is changed in the process, the clinical protocol before and after the change and its ethics documents shall be submitted together, and the reasons for the protocol change and its impact on the conducted clinical trial shall be clearly explained.It should be noted that before the clinical trial, the scientificity, rationality, feasibility and compliance of the protocol should be fully studied, the protocol should be formulated and strictly implemented. During the clinical trial, the protocol shall not be changed at will for unnecessary reasons.
Can radiation protection accessories for X-ray diagnostic equipment be declared together with diagnostic equipment?
Accessories for radiation protection, such as radiation protection clothing, radiation protection cap, radiation protection skirt, radiation protection collar, medical radiation protection glasses, etc., are used for the protection of human body during radiation diagnosis. Such protective accessories usually are connected with active equipment by no power connection or other physical connection. They are managed separately as medical devices in the classification catalogue and are recommended to be declared separately. Except for non-removable accessories.
What dossiers need to be submitted for the modification application of in vitro diagnostic reagent packaging specification?
If the packaging specification of in vitro diagnostic reagent changes, the difference of packaging specification before and after the change shall be described in detail. All relevant potential risks shall be identified according to the specific differences, and these risk factors shall be analyzed and verified. Some examples are as below:
if there are differences in the reaction form (such as poison detection products) and reaction film size (such as PCR amplification and hybridization products) of the packaging specification before and after the change, the analysis performance evaluation dossiers of the changed packaging specification shall be submitted.Before and after the change, the amount of packaging specifications and containers will change significantly, which will lead to the increase of evaporation loss and other risks. Therefore, it is necessary to consider whether the shelf life, stability and calibration frequency of the product will change.
Whether liquid products for in vitro assisted reproduction can carry out clinical evaluation through CER?
Some liquid products for in vitro assisted reproduction have entered the Catalogue of Medical Devices Exempted from Clinical Trials. For the products that are not in the catalogue, it is recommended to select appropriate clinical evaluation paths, including clinical trials and CER pathway, based on the actual characteristics of the declared products and the available supporting dossiers.
If the products that use CER or clinical trial pathway for clinical evaluation have been listed in the published exemption directory during the review, can the clinical evaluation pathway be changed when the applicant supplements the dossier?
The technical review of clinical evaluation of medical devices is carried out based on the clinical evaluation dossiers submitted by the manufacturer. If CER or clinical trial pathway is adopted for the clinical evaluation of the medical devices under review, for example, after the applicant submits the registration application dossiers, the declared products are listed in the officially released catalogue of medical devices exempted from clinical trials, and the applicant can complete the clinical evaluation through the catalogue of medical devices exempted from clinical trials according to its needs when supplementing the dossiers. In this case, considering the significant changes in the clinical evaluation dossiers in the supplementary dossiers compared to the initial submission, the applicant can communicate with the reviewers through communication channels including post supplementary consultation and preliminary review.
When assessing limits of detection (LoD) for in vitro diagnostic reagents, what if LoD results differ from batch to batch?
Detection limit (LOD) is an important performance index of in vitro diagnostic reagents. Generally, three batches of reagents are used for LOD research. If the LOD results differ from batch to batch (generally there should be no significant difference), the maximum value or higher value shall be taken as the claimed LOD of the reagent to ensure that all batches of reagents meet the claim.
