Essential requirements for clinical evaluation of in vitro diagnostic reagents free from clinical trials

Pharmaceutical Network November 9 In order to implement the "Opinions on Deepening the Innovation of Medical Device Innovation for Drug Evaluation and Approval System" (Office Word [2017] No. 42) issued by the General Office of the CPC Central Committee and the General Office of the State Council and the "Opinions of the State Council on Reform (Guofa [2015] No.44) to further improve the registration management of in vitro diagnostic reagents and to standardize the clinical evaluation of in vitro diagnostic reagents from clinical trials. According to the provisions of the Measures for Registration of In vitro Diagnostic Reagents (SFDA Order No. 5) and the State Food and Drug Administration formulated the "Basic Requirements for Clinical Evaluation of In Vitro Diagnostic Reagents Exempted from Clinical Trial (Trial)", which is hereby promulgated and released since its release The date of implementation.

announce.

Annex: Essential requirements for clinical evaluation of in vitro diagnostic reagents exempt from clinical trials (Trial)

food drug Regulatory Authority

November 3, 2017

annex

According to the provisions of Article 29 of the Administrative Measures for the Registration of In Vitro Diagnostic Reagents (Order No. 5 of the State Food and Drug Administration), an applicant for in vitro diagnostic reagents that does not need to conduct clinical trials shall, Interfering clinical evaluation of clinical samples, comprehensive literature and other non-clinical trials to evaluate the clinical performance of in vitro diagnostic reagents.In order to guide the registration of applicants for clinical evaluation of in vitro diagnostic reagents and food and drug regulatory audit of clinical evaluation of the information Comment, make this requirement.

Application for product registration and change application involving clinical evaluation for entering the IMRT catalog (hereinafter referred to as "catalog") which is exempt from clinical trials is applicable to this requirement. "Catalogs" do not differentiate methodologies when there are no specific explanations.

If the applicant is unable to carry out the clinical evaluation of the products in the directory according to the requirements, the clinical trial should be conducted.

The following cases do not apply, clinical trials should be conducted in accordance with the "guidelines for clinical trials of in vitro diagnostic reagents" requirements:

(A) 'directory' products due to methodological updates, product design updates and other reasons can not achieve a clear response to the principle of design stereotypes, the production process is mature.

(B) the product in the 'catalog' changes its routine intended use.

(C) self-test consumer self-diagnostic reagents.

(I) Clinical evaluation of in vitro diagnostic reagents by the applicant or commissioned by other agencies or laboratories in China to complete the test process by the applicant management, the authenticity of the test data is the responsibility of the applicant.Overseas applicants through its in China Domestic proxy People, to carry out the relevant clinical evaluation.

(B) According to the characteristics of the product applicant can choose the test site to complete the sample test, test site facilities, test equipment, the environment should be able to meet the product testing requirements.

(C) the applicant should establish a reasonable clinical trial program and follow the implementation of the trial.

(D) experimental operators should be professional and technical personnel.

(5) Samples for evaluation should be human-derived samples, and the source of samples should be traceable. Samples for evaluation (cases) The original data should include at least the following information: sample source (including receiving collection records), unique and traceable number , Age, gender, type of sample and clinical background information of the sample. Products that have a clear disease point for the test result of the reagent should include clinically definite diagnostic information.

(F) After the test is completed, the clinical performance evaluation results of the product are summarized to form a clinical evaluation report which is submitted as a clinical evaluation data at the time of registration Other relevant data of clinical evaluation such as test plan, original record, etc. are kept by the applicant for storage, 10 years.

The applicant shall, based on the specific circumstances of the declared product, establish an appropriate evaluation method, fully consider the intended use of the product, and carry out a targeted evaluation study, choosing one of the following two evaluation approaches.

(A) with the domestic market similar products have been comparative study of the test to prove that the two have the same effect should be selected at present generally considered good clinical quality products as a reference reagent, and should fully understand the technical information of the reference reagent, including methodologies , Clinical intended use, main performance indicators, traceability of calibration products, recommended positive judgment value or reference interval, etc., domestic registration information of listed products and manuals should be provided.

(B) comparative study with the reference test method to examine the evaluation of reagents and reference methods to be consistent with the rate / consistency should be selected reference laboratory research, reference laboratories should have the China National Accreditation Board for Conformity Assessment (CNAS) recognized the relevant Testing qualification.

The establishment of the test method can refer to the relevant guiding principles of methodological comparison, and focus on the following:

(A) sample requirements

1. Select the sample covering the intended use and interference factors for evaluation research, give full consideration to the test population selection, disease selection and other content, the sample should be able to fully evaluate the safety and efficacy of the clinical use of the product.

2. The number of samples should be calculated using reasonable statistical methods, should meet the statistical requirements.Quantitative products can choose the total sample size of not less than 40 cases, and were used to be evaluated reagents and contrast reagents / reference method for double determination of the way , Of which the sample outside the reference interval should not be less than 50%, can also choose the total sample size of not less than 100 and were used to be evaluated reagents and contrast reagents / reference method for a single determination of qualitative products should meet at least 50 cases Positive samples and 50 negative samples before the experiment should set the clinical evaluation of performance indicators acceptable standard If the results of the comparative study fail to meet the preset criteria, the sample size should be appropriately enlarged for evaluation.

3. Quantitative test products should focus on the choice of the sample size near the medical decision level, and cover the scope of the test, such as the need for stratified statistics and other complex situations, should be based on the actual situation to select the appropriate sample size for full clinical evaluation. Should pay attention to the positive selection value near the sample selection.

4. The type of sample for evaluation should be consistent with the application for registration. For non-comparable types of samples, such as blood samples and urine samples, a statistically significant number of assessments should be performed separately. For comparable samples Types, such as serum and plasma samples, may be studied for sample suitability in analytical performance assessments, or statistically, for each sample type, in clinical evaluation.

(B) test points

1. Blind method should be used during the test operation, the reagents to be evaluated and the reference reagent / reference method should be operated in parallel, and the whole test should have internal quality control.

2. It is recommended to test the quantitative product testing cycle at least 5 days, 10-20 days testing cycle qualitative products to objectively reflect the actual situation.

3. Increasing the sample size and prolonging the test period will increase the reliability of the test. Applicants should select the appropriate sample size for adequate clinical evaluation.

(C) data collection and processing

1. For the quantitative detection of products, should be the first outlier observation, the number of outliers should not exceed the limit.If it is not overrun, you can delete outliers after analysis; if the limit is exceeded, you need to reason a reasonable analysis of the reasons And consider corrective measures, if necessary, re-collect samples for analysis.Individual value analysis and processing methods should be based on.

Applicants should select the appropriate statistical methods based on product characteristics, statistical results should be able to confirm the evaluation of reagents to be compared with the reference reagent / reference method no significant bias or deviation within the allowable error range.

2. For qualitative products, the two groups of test results should be consistent assessment, combined with clinical diagnostic information using a reasonable method for statistical analysis of inconsistent samples should be confirmed by reference to methods or clinical diagnostic information.

The clinical evaluation report should clearly describe the test design, test implementation and data analysis methods, etc. The following should be included:

(A) basic information, such as product name, name and contact details of the applicant, test time and place.

(2) The test design specifies the contents of comparative reagents / method selection, sample inclusion and exclusion criteria, sample size requirements, blindness requirements and the selection of statistical analysis methods.

(C) test implementation, including:

1. Sample selection, including the number of cases, sample distribution, etc. The sample number should specify the calculation method and basis.

2. Product information for clinical evaluation, such as product name for other reagents / instruments used for evaluation, comparison reagents / methods, production enterprise , Specifications / model, batch number and so on.

3 experimental process description.

4. Test management, including participants, quality control, data management, problems and solutions.

5. Data analysis and evaluation results summary, according to the statistical methods to determine the statistical analysis of test data, the clinical performance of the product a reasonable evaluation.

6. Evaluation Data Sheet

The summary of the samples in the group should be summarized as an attachment and should include at least the following information: traceable sample number, basic sample information, type of sample, evaluation reagents and comparative reagents / method test results, sample clinical background information or clinical diagnosis Information (if applicable) and so on.

7. The evaluation report should be signed by the applicant / agent.

In addition to the above clinical evaluation report, the relevant literature on the evaluation of the clinical performance of the proposed product may be submitted as supplementary clinical evaluation data. For the search, screening and analysis of the literature,medical instruments Clinical evaluation of technical guidelines "for the literature search requirements.