Technical Guidelines For Accepting Data On Overseas Clinical Trials Of Drugs

A&Z’s interpretation

In order to strengthen the guidance and regulation pertaining to the acceptance of overseas clinical trial data, the State Drug Administration has recently formulated and published the Technical Guidelines for Accepting Data from the Overseas Clinical Trials of Drugs.

With the increasing globalization of drug research and development, an increasing number of multinational and domestic companies are seeking to support global registration applications through international multi-center clinical trials in order to plan global market strategy. With the release of these Technical Guidelines, of the most concern to pharmaceutical companies and the public is that drug registration applicants can submit overseas clinical trial data when applying for drug registration in China. This also means that new drugs that have been approved for listing overseas can be listed in China more quickly, shortening the length of time between drugs being listed abroad and at home.

The new guidelines can guide pharmaceutical companies to carry out simultaneous research and development of drugs inside and outside of China, reducing unnecessary repetition of research and accelerating the listing of drugs with urgent clinical needs, controllable safety risks, and curative effects, so as to better meet the drug needs of domestic patients.

The guidelines clearly define the scope of application, basic principles, integrity requirements, technical requirements for data submission, and the acceptance of data received from overseas clinical trials.

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Technical guidelines for receiving data on clinical trials of drugs abroad

1. Scope

These guiding principles are applicable in guiding applicants in the use of overseas clinical trial data as clinical evaluation data when applying for drug registration in the territory of the People's Republic of China.

The overseas clinical trial data covered by these guidelines includes, but is not limited to, clinical data obtained abroad pertaining to innovative drugs which have undergone simultaneous research and development both within and outside of China. Generic drugs developed outside of China, with fully evaluable bioequivalence data, can also be used for registration applications.

2. Basic principles for accepting data from overseas clinical trials

Applicants should ensure the authenticity, completeness, accuracy and traceability of data from overseas clinical trials.

The process of generating clinical trial data outside of China shall comply with the relevant requirements of the International Conference on Harmonization of Human Drug Registration Technology (ICH) Good Clinical Practice (GCP).

Applicants should ensure that the scientific design of overseas clinical trials as well as the quality management system of clinical trials meet such requirements, and that the statistical analysis of data is accurate and complete.

In order to ensure that the clinical trial design and statistical analysis of the data are scientific and reasonable, with regard to the domestic and foreign drugs for which clinical trials will be carried out in China, the applicant may communicate with the Drug Review Center of the State Food and Drug Administration (SFDA) before implementing key clinical trials, to ensure that the design of key clinical trials meets the basic technical requirements of Chinese drug registration.

3. Accepting the integrity requirements for overseas clinical trial data

When using overseas clinical trials for Chinese drug registration applications, all of the clinical trial data should be provided, rather than selectively provided. Ensuring the integrity of clinical trial data is a basic requirement for the acceptance of registration applications.

Where early clinical trials have already been conducted abroad, and subsequent clinical research and development is to be carried out in China, the drug registration applicant should evaluate the early clinical trial data. If the data is complete, after communicating with the drug trial center it can be used to support subsequent clinical trials.

For all clinical trials that have been completed overseas but the drugs have not yet been listed there, a complete overseas clinical trial data package must be provided; for drugs already listed, updated safety and validity data must be provided before the drug can be registered in China.

4. The submission of overseas clinical trial data and basic technical requirements

When submitting a drug registration application concerning synchronous domestic and foreign clinical research and development, both the domestic and foreign clinical trials should be compiled according to the application requirements of the Drug Registration Management Measures. Only a complete clinical trial data package can be used in a registration application for drugs in China.

Overseas clinical trial data submitted for Chinese drug registration applications should include biopharmaceutical, clinical pharmacology, efficacy, and safety data. Applications for drug registration are encouraged to be submitted in the General Technical File format (CTD).

Biopharmaceutical data must include important in vitro or in vivo data related to bioavailability and bioequivalence, providing a support basis and data linkage for formulation determination and optimization of preparation processes during clinical development.

Regarding clinical pharmacology data, including pharmacokinetic and pharmacodynamic data, drug registration applicants should conduct racial sensitivity analyses from a variety of perspectives, such as regional and ethnic, to support the application of overseas clinical trial data to the Chinese population, and to support effectiveness and safety evaluations.

The effectiveness data, including key clinical trial data from abroad and data from clinical trials conducted in China, should not only confirm the validity of the study drug as a whole, but also analyze the consistency of the Chinese subgroup with the general population.

The safety data, including all domestic and foreign data for safety assessments, should analyze both overall safety and the consistency of the Chinese subgroup with the general population.

The data of overseas clinical trials should support the evaluation of effectiveness and safety. Applicants for drug registration should consider complying with the requirements of Chinese drug registration management. Based on the analysis of the complete clinical trial data package, the key clinical trial data is evaluated to confirm the effectiveness of the research drug; follow the ICH requirements for ethnically influenced factors (E5) for receiving clinical data from abroad, and analyze the consistency of the Chinese subgroup with the general population to support the extrapolation of overseas clinical trial results to the Chinese population.

5. Acceptability of overseas clinical trial data

The acceptance of clinical trial data is divided into three levels: fully accepted, partially accepted and not accepted. The level depends on the quality of the clinical trial data.

Fully accepted: the overseas clinical trial data are authentic and reliable, and in line with ICH GCP and drug registration check requirements; overseas clinical research data support the effectiveness and safety evaluation of target indications; there are no ethnic sensitivity factors that affect effectiveness and safety.

Partially accepted: the data of overseas clinical trials are authentic and reliable, and in line with ICH GCP and drug registration check requirements; overseas clinical research data support the effectiveness and safety evaluation of target indications. However, there are racial sensitivity factors that affect effectiveness and/or safety. There is considerable uncertainty in the evaluation of the effectiveness and safety of data from overseas clinical trials extrapolated to the Chinese population. Drug registration applicants should analyze the situation according to the influencing factors, and communicate with the drug testing center to conduct relevant targeted clinical trials.

Not accepted: the data of overseas clinical trials have major problems in terms of authenticity, completeness, accuracy and traceability. The data of overseas clinical trials cannot fully support the validity and safety evaluation of target indications. Drug registration applicants should follow innovative drug research and development thinking, and conduct systematic clinical trials in China to support drug registration applications in China.

Regarding applications for the registration of drugs for critical illnesses, rare diseases, pediatrics, and for which there is a lack of effective treatment methods: after assessing the data for clinical trials carried out outside of China and deeming a "partial acceptance", it is acceptable to use conditional clinical trial data to collect further validity and safety data for evaluation after the listing of drugs.

 (Source: National Drug Administration)