The China Drug Administration ("CDA") issued the Technical Guidelines and Principles for Accepting Overseas Clinical Trial Data of Drugs ("Overseas Trial Data Principles") on 6 July 2018 and published such guidelines on 10 July 2018.
The Overseas Trial Data Principles cover the following:
1. Scope of the Overseas Trial Data Principles
The Overseas Trial Data Principles are applicable to guide the process of applications for market authorisations ("MA") of drugs in China when such data is submitted to support clinical evaluation.
Examples of overseas trial data that will be accepted include:
(i) clinical trial data of innovative new drugs simultaneously developed in China and overseas; and
(ii) clinical trial data of generic drugs researched and developed overseas possessing fully measurable bioequivalence ("BE") data.
2. Basic Principles in Accepting Overseas Clinical Trial Data
Applicants shall ensure the authenticity, completeness, accuracy and traceability of overseas clinical trial data.
The process of generation of overseas clinical trial data shall comply with relevant requirements set out in Good Clinical Practice ("GCP") of the International Harmonisation of Technical Requirements for the Registration of Pharmaceuticals for Human Use ("ICH").
Applicants shall ensure that:
(i) overseas clinical trials are designed scientifically;
(ii) the system of quality management of clinical trials comply with relevant requirements; and
(iii) the statistical analyses of clinical trial data are accurate and complete.
For ensuring the scientific soundness and reasonableness of clinical trial designs and statistical analyses of data in respect of drugs simultaneously researched and developed outside China and in China, applicants may communicate with the Center for Drug Evaluation ("CDE") of the CDA before the implementation of critical clinical trials in order to ensure that the designs of critical clinical trials are compliant to the basic technical requirements of drug registration in China.
3. The Completeness Requirement in Accepting Overseas Clinical Trial Data
Overseas clinical trials used in applications for MAs in China shall provide all clinical trial data obtained overseas in full and should not be selectively provided. Ensuring the completeness of clinical trial data is the basic requirement in accepting applications for MAs.
For drugs that have already undertaken early clinical trials outside China with subsequent clinical research and development conducted in China, applicants shall conduct evaluation on their early overseas clinical trial data . In cases where applicants possess complete overseas clinical trial data and communicate with the CDE, such overseas clinical trial data may be used to support the subsequent continuation of clinical trial in China.
For those drugs where all clinical trials have been completed overseas but have not been marketed anywhere in the world, the complete overseas clinical trial data should be provided; if the drugs are already marketed, updated data in safety and efficacy should be provided so the overseas clinical trial data can be used in applications for MAs in China.
4. Guidance on Submission and Basic Technical Requirements of Overseas Clinical Trial Data
For drugs that have undergone simultaneous clinical research and development in China and overseas, all clinical trials in China and overseas should be consolidated in accordance with the Administrative Measures for Drug Registration to form a complete dossier of clinical trial data, which may then be used in the applications for MAs in China.
Overseas clinical trial data used in support of applications for MAs in China should include information and data on biopharmaceutics, clinical pharmacology, efficacy and safety of the drugs as further explained below:
1. Biopharmaceutics data should consist of relevant in vitro and in vivo data and results in bioavailability and BE studies in order to provide basis of support and data consistency between the definition of formulation and preparation process optimization during clinical research and development.
2. Data in clinical pharmacology mainly include pharmacokinetic ("PK") data and pharmacodynamic ("PD") data. Applicants shall conduct racial sensitivity analyses from a variety of perspectives, such as regional and ethnicity, etc., to support overseas clinical trial data for the Chinese population, and to support the evaluation of efficacy and safety of the drugs.
3. Efficacy data mainly include critical overseas clinical trial data and clinical trial data obtained in China.
4. Safety data include all data used in safety evaluation in China and overseas.
Applicants shall comply with the Chinese drug registration requirements to conduct evaluation on critical clinical trial data in order to confirm the efficacy of the drugs under research. Applicants should also comply with the ethnically influential factors in relation to accepting overseas clinical information (E5) required under the ICH in order to analyse the consistency between the Chinese population and the overall worldwide population, in particular for data in clinical pharmacology, efficacy and safety, such that overseas clinical trial data are applicable to the Chinese population.
Applicants are encouraged to use general technical document format (CTD) for submissions.
5. Acceptability of Overseas Clinical Trial Data
Based on the quality of overseas clinical trial data, the acceptance by the CDA of such data will be divided into three categories: (a) fully accepted; (b) partially accepted; and (c) rejected.
(a) Fully accepted
Overseas clinical trial data are true and reliable, in line with the GCP of the ICH and drug registration requirements; overseas clinical research data support the evaluation of efficacy and safety of target indications; there are no ethnic sensitivity factors affecting efficacy and safety.
(b) Partially accepted
Overseas clinical trial data are true and reliable, in line with the GCP of the ICH and drug registration requirements; overseas clinical research data support the evaluation of efficacy and safety of target indications, but there are ethnic sensitivity factors affecting efficacy and/or safety i.e. there is uncertainty in the evaluation of the efficacy and safety of overseas clinical trial data applied to the Chinese population. In such cases, applicants should communicate with the CDE and target the implementation of corresponding clinical trials in China to address these uncertainties.
There are major problems in the authenticity, completeness, accuracy and traceability of overseas clinical trial data. Overseas clinical trial data do not adequately support the evaluation of efficacy and safety of target indications. Applicants should conduct systematic clinical trials in China in accordance with the research and development practice of innovative drugs to support their applications for MAs in China.
Where overseas clinical trial data are "partially accepted" for applications for MAs of drugs for critical diseases, rare diseases, paediatrics that do not have effective treatment, a conditional acceptance of the overseas clinical trial data may be granted subject to the collection of further efficacy and safety data for evaluation after MAs are granted.
This is part of CDA's continued efforts to introduce reforms as outlined in the Opinions on Deepening the Reform of the Review and Approval System to Encourage Innovation in Drugs and Medical Devices jointly issued by the Central Committee of the Communist Party and the State Council of China (Ting Zi (2017) No.42). Life Sciences companies should review these guidelines clearly as this will affect the applications for MAs in China.