Technical Guidelines of use IVD overseas Clinical Trial Data (draft for comment)

Background

In vitro diagnostic reagents (IVD) as a special medical device, play an important role in the marketing process with the acceleration of product innovation. When using overseas clinical trial data as clinical evidence for China's registration and application, it is necessary to analyze its rationality and adequacy to determine whether overseas clinical trial data can be used as clinical evidence for China's registration and application, and whether further domestic and foreign clinical trial data are required.

This guide is to clear that there are few aspect need to be considered carefully when using the overseas in vitro diagnostic reagent (IVD) clinical trial data during product registration in China.

I. Limits

The circumstance of this guidance is when applicant use overseas clinical trial data as their IVD clinical evidence for the registration in China. It is applicable to the application for the first registration and the change of related licensing items.

II. Key considerations for differences between domestic and foreign clinical trials

(i) The discrepancy of clinical trial quality management requirements

Applicants should focus on the following:

1. Whether overseas clinical trial institutes have complete quality management requirements for clinical trials in national (regional) regulatory authorities;

2. When conducting clinical trials, whether overseas clinical trial institutions have carried out strict clinical trial quality management as required;

3. Whether there is any difference in the quality management of clinical trials of in vitro diagnostic reagents between the countries (regions) where the overseas clinical trials are conducted and China; If so, whether it leads to differences in clinical trial data.

(ii) Differences in key elements of clinical trial design

1. The discrepancy of clinical institution and personnel (clinical trial conditions)

- clinical institutions

Differences in clinical trial institutions should be concerned with differences in the number, qualifications or conditions of such institutions. For example, China requires class II or Class III in vitro diagnostic reagents to be tested in at least 2 or 3 clinical trial institutions, respectively.

- clinical trial personnel

For the self-tested products available to non-professionals and the interpretation of the results by the clinical testers, such as the structured products

2. Comparison methods/reagent differences

- If clinical reference standards are used as the comparison method in overseas clinical trials, the applicant should pay attention to the differences between domestic and foreign clinical reference standards (e.g. actual operation and result interpretation, etc.).

- If similar products are used as comparison reagents in overseas clinical trials, the applicant should pay attention to the marketing status of the comparison reagents used in China, and the applicant should use similar products already on the market in China as comparison reagents.

3. The discrepancy of sample size

- Domestic and foreign regulators may have different requirements for the sample size of specific products. The applicant should pay attention to whether the sample size of the overseas clinical trial meets the relevant requirements of China's general guidelines and specific product guidelines, etc. If not, the clinical trial should be supplemented abroad or in China as the case may be.

4. The discrepancy of subjects

- Differences in genetic information between races

- Differences in disease characteristics

- Differences in the prevalence of pathogens among the subjects

5. Differences in clinical trial samples and statistical analyses

- For some products, the difference in sample collection, storage and processing may lead to the difference in sample quality, leading to the difference in clinical trial data. The applicant shall supplement the clinical trial within the Territory of China.

- For some products, there may be differences in the statistical analysis of domestic and foreign clinical trial results, leading to differences in domestic and foreign clinical trial data. The applicant shall make statistical analysis according to the relevant requirements of China.

6. The difference with our country specific product guiding principle

- The applicant should also pay attention to whether the overseas clinical trial design meets the specific requirements of China's relevant product guidelines. If not, the clinical trial should be supplemented in China or abroad as the case may be.

III. Treatments

(i)If it is found after analysis that the overseas clinical trial data fully support the intended use of the declared product registered in China and meet the relevant requirements for the registration of clinical trials in China, the overseas clinical trial data can be taken as sufficient clinical evidence for the registration and application in China.

(ii)If it is found after analysis that the overseas clinical trial data cannot fully support the intended use of the declared product registered in China and cannot meet the relevant requirements for the registration and application of clinical trials in China, the overseas clinical trial data can be taken as part of the clinical evidence for the registration and application in China. The applicant should supplement the clinical trial within or outside China as appropriate.

(iii)If it is found after analysis that the overseas clinical trial data cannot support the intended use claimed by the registered product in China, or meet the relevant requirements for the registration of clinical trials in China, then the overseas clinical trial data cannot be used as clinical evidence for the registration in China. The applicant shall carry out clinical trials in or outside China as required.

IV. Data requirements for the use of overseas clinical trial data

(i) The applicant shall specify the purpose of the overseas clinical trial data, whether the overseas clinical trial data are complete and included in the Chinese population data, and whether the applicant and the clinical trial institution are willing to accept the supervision and inspection by China Drug Administration.

(ii) The applicant shall submit the ethical opinions, clinical trial protocols and clinical trial reports of the overseas clinical trial institution. The submission form, content, signature and seal of the ethical opinions, clinical trial protocols and reports should meet the requirements of local clinical trial quality management. The applicant shall provide complete clinical trial data, without screening, and the clinical trial report shall contain an analysis and conclusion of the complete clinical trial data. Overseas clinical trial data should be authentic, scientific, reliable and traceable.

(iii) The applicant shall also submit the discrepancy analysis report of domestic and foreign clinical trials, which shall include the analysis and treatment of the above differences.