On October 8, the General Office of the CPC Central Committee and the General Office of the State Council issued "the Reformed Examination and Approval System of CFDA to Promote Drug and Medical Device Development and Innovation", and required all localities and departments to implement. This is followed by the regulation issued in August 2015, "the State Council on the reform of drug medical device examination and approval of the views of the system,” after another document of deepening drug and medical device review and approval system reform program. This is important for the development of the innovations of China's pharmaceutical industry.
Its objectives are (1) to promote the re-structuring of industrial and the technological innovation of pharmaceutical and medical device industry, (2) to improve the competitiveness of the industry, (3) to meet the clinical requirements so that we improve the review and approval system, and (4) to encourage the innovation of pharmaceuticals and medical devices.
The succeeding sections of the article highlights the parts of the CFDA document which will impact the medical device industry, followed by a brief interpretation. For the complete article, please see the complete article from the CFDA website.
I. Reform of Clinical Trial Management
(1) To implement and record the eligible clinical trial institutions
The main investigators in clinical trials should be a senior staff and should have participated in more than three clinical trials. The applicant could appoint a third party to evaluate the certification of the clinical trial institution. We encourage the industry to invest in setting up clinical trial institutions.
Interpretation:
To widen the certificate limitation of clinical trial institutions.
(2) Support clinical trial institutions and staff to carry out clinical trials
Improve the incentive mechanism with the distribution of unit performance and wage to ensure the competitive salary level of clinical trial researchers. We shall encourage clinicians to participate in medical device technology innovation activities, level up the position of the clinical trial researchers, and treat them like clinicians. Moreover, we allow the foreign enterprises and scientific research institutions to carry out clinical trials of new drugs and medical device in China in accordance with the law.
Interpretation:
There will be increased support to clinical trial institutions to increase the enthusiasm of clinical researchers, to change the stigma that clinical trial is a difficult and high-risk investment.
(3) Improve the mechanism of the ethics committee
Local ethics committees can be set up to guide the ethical review of clinical trials.
(4) Enhance the efficiency of ethical reviewing
The applicants shall submit the clinical trial program to the ethics committee for reviewing and get the approval before the clinical trial application. If the clinical trial is carried out in multiple clinical trial sites, the ethics review is implemented by the head unit of clinical trial institution, the other member units shall accept the conclusion from the head institution, rather than repeating the ethics review. National Clinical Medical Research Center and the clinical trial institution having the national technology major projects and the national major R&D program shall integrate resources to establish a unified ethical review platform, and gradually promote the mutual recognition of ethical review.
Interpretation:
The applicants only need the approval of the ethics reviewing from the head unit of clinical trial institution before undergoing the multi-center studies. This change would greatly shorten the clinical trial implementation timeline.
(5) Optimize the clinical trial approval process
Within a certain period of time after acceptance of the clinical trial application, if the food and drug regulatory authorities do not give negative or doubtful comments, then it means that the authorities agree with this clinical trial plan, and the registered applicant can carry out the clinical trial in accordance with the submitted plan. At the same time, CFDA would optimize the approval process for international corporations involving human genetic resources to speed up the clinical trial process.
Interpretation:
The implied permission system improves the efficiency. In addiotion, CFDA speeds up the clinical trial process through speeding up the genetic declaration cycle.
(6) Overseas clinical trial data becomes acceptable
The clinical trial data obtained from overseas centers, which are in compliance with the relevant requirements for the regulation of Chinese pharmaceutical medical devices registration, can be used for registration in China. For drugs and medical devices which are to be registered for the first time in China, the applicant shall provide the clinical trial data for the presence of ethnicity differences.
Interpretation:
1) Accepting overseas clinical trial data is conditional and shall meet the requirements for registration in China, and shall also prove that there are no ethnicity differences for the device.
2) The purpose of carrying out international multi-center studies is to reduce the repetition of clinical trials, to improve efficiency, to reduce the cost of research and development, and to decrease the delay of foreign medical devices which be registered in China. In the future, CFDA will improve the guideline of the clinical trial data management, through clearly identifying which can or cannot be accepted.
3) To strengthen the supervision and inspection of clinical trials, the CFDA does not only accept, but can also send inspectors to overseas clinical trial institutions for on-site inspection. Through establishing the inspection mechanism of the overseas clinical trial, CFDA would gradually increase the inspection threshold of foreign clinical trials to ensure that the foreign clinical trial data is accurate. The person who signs the clinical trial agreement and investigators are the first person that need to be legally responsible for the reliability of clinical trials data.
(7) Support the clinical trials of particular disease
For the medical devices for the treatment of life-threatening diseases and without established effective therapy, after the primary reviewing, the clinical trial can be expanded to other patients in the clinical trial institution, and the safety data can be used for registration. This is because of the potential to obtain beneficial treatments, as long as they meet ethical requirements.
(8) Serious investigation and prosecution of fraudulent data
The person who signs the clinical trial agreement and investigators have primary responsibility for the reliability of clinical trial data legally. If a reliability problem arises, CFDA shall start the investigation immediately, and call to action the relevant non-clinical research institutions, clinical trial institutions’ responsible person, the responsible person who provided the false report, the applicant and the contractor responsible for the responsibility of the contract. Any person or party who refuses, tries to escape, and interferes with the investigation would be severely punished based on the relevant regulation.
Interpretation:
CFDA issued the policy for fraudulent reports. The person who fabricates or fakes the clinical data would be severely punished according to the law.
II. Speeding Up of the Listing Review and Approval
(9) Another reason behind this move is to speed up the clinical evaluation of medical equipment and their regulatory approval. This is to benefit the treatment of serious life-threatening diseases, taking care of public health and attend to the other urgent needs that require these medical equipment. Apart from that, the meidcal device, which clinical trials early and mid-term indicators show efficacy and can predict its clinical value, can be approved for listing with the conditions. However, enterprises shall develop risk management plan to carry out research as required. This reformation also supports priority examination and approval of new drugs and innovative medical devices, which are also supported as national science and technology major projects and national key Research and Development programs and clinical trials conducted by the National Center for Clinical Medicine and approved by the central management department.
(10) This major reformation is also intended to support the treatment of rare disease by investing in of innovative and novel medical device research and development. Foreign-manufactured medical devices that have been approved for listing abroad have a good chance of getting approved for listing in China, as well. For that, the manufacturer have to establish a proper risk management plan and carry out research as required.
Interpretation:
This change is intended to support the development and release of a list of rare diseases, for rare medical devices can be exempted from clinical trials, with the conditions permit approval.
IV. Strengthening the Life Cycle Management of Medical Equipment
(22) This reform is also to promote the full implementation of the license system listing, allowing medical device R & D institutions and researchers to apply for medical device licensing.
(23) Furthermore, in conjunction with the license system listing, to implement the legal responsibility of the listed licensee, Medical Device Licensing Owner shall bear all legal liability for medical device design and development, clinical trials, manufacturing, sales distribution, adverse event reports, and etc., to ensure that the submitted research data and clinical trial data are true, complete and traceable. The listed medical devices must be subjected to continuous research, timely reporting of adverse events, risky situations assessed, and improvement measures proposed, as well. The licensee of the listed license shall, on the basis of the scientific progress and the assessment result of the adverse events, take the initiative to re-evaluate the listed medical device. If the re-evaluation of the results appear different from original, the manufacturer must take the initiative to cancel the application. If this is not done, their listing license could be revoked and investigated and dealt with according to law. The enterprises, institutions and individuals entrusted to the R & D, clinical trial, manufacturing and sales distribution shall be responsible for the responsibilities and agreements stipulated in the laws and regulations.
Interpretation:
The licensee of the listed license shall bear all the legal liability and the entrusted party shall assume the responsibility of the agreement.
(24) The establishment of listed license holders are responsible to directly report adverse reactions and adverse events.
(26) Improve the medical device re-evaluation system.
V. Enhancing Technical Support Capacity
(28) Improve the technical review system. The establishment of a review-oriented inspection would dominate the review system and technical testing would be a supportive role within the technical review system. This would develop a completeness of the project manager system, review agencies and registration applicant’s conference communication system, expert advisory committee system, strengthen internal management, and standardize the review process. The medical device review team, which consists of professionals such as clinical medicine, clinical diagnosis, mechanical, electronic, materials and biomedical engineering, is responsible for the evaluation of innovative medical devices. In addition to production technology and other technical secrets, the review conclusions and based on all open, accept social supervision. Unified the second category of medical equipment review standards, and gradually achieve national unified review.
Interpretation:
CFDA is strengthening the capacity-building of medical device review institutions by conducting team review and is responsible for the review of innovative products. This will increase the number of reviewers, expand the team of reviewers, and strengthen the training and establishment of a professional team of reviewers. The two documents are also meant to actively promote the second category of medical equipment, to reinforce the unity of the review criteria, and to gradually achieve a national unified review.
(29) The implementation of the relevant staff confidential responsibility. Those who participate in the supervision and examination of drug medical equipment, review and approval, inspection and other supervision work, the registration of the applicant to submit the technical secret and test data with confidential obligations.
(30) To strengthen the review and inspection capacity-building. The drugs and medical device review is added into the scope of government procurement services, to provide standardized and efficient review services. This would accelerate medical device review and approval of information construction, developing electronic applications that is submitted to apply for technical requirements, improving the electronic general technical documentation system, and gradually realizing the various types of registration applications for e-submission, review, and approval. The establishment of listed drugs and medical device database.
Interpretation:
CFDA will require the appliant to submit electronic documents for review and approval afterwards in order to be unified internationally.
(31) To fulfill the whole process of inspection responsibility. Medical device development process and medical device clinical trial quality management practices (GCP) implementation are inspected by the national food and drug regulatory authorities. Medical device production process and production quality management practices (GMP) implementation are also inspected by the regional food and drug regulatory authorities. Medical device business process and management of quality management practices (GSP) implementation are inspected by the county and county levels of food and drug regulatory authorities. If a problem is found, the risk control measurement shall be taken according to the regulations, and shall be investigated according to the law and criminal control. To promote the punishment of violations to people, inspection and punishment results will reveal to the public.
Interpretation:
In the future, GCP, GMP, GSP inspection efforts will increase, punishment will tend to be severe.
(33) To strengthen international cooperation. Deepen the policy of bilateral pharmaceutical medical equipment supervision and technical exchanges, and actively participate in the development of international rules and standards to promote the progressive realization of the review, inspection, inspection standards and results of international sharing.
VI. Strengthening the Organization and Implementation
(34) To strengthen the organization and leadership, cooperation, publicity and sufficient explanation are used to reach the goal. The relevant departments of various regions should fully understand the importance of deepening the reform of the examination and approval system to encourage the innovation of pharmaceutical and medical devices for building an innovative country to promote the development of high-tech industries.
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