NMPA has released three heavyweight documents, including the Breakthrough Therapeutic Drug Review Process.

Just now, the State Drug Administration has issued three heavyweight documents, "Breakthrough Therapeutic Drug Review Procedure (Trial)" "Review and Approval Procedure for The Approval of Drug Conditional Approval Applications for Listing (Trial)" and "Priority Review and Approval Procedure for Drug Listing Permits (Trial). Effective from the date of publication. The "Opinion on The Priority Review and Approval of Encouraging Drug Innovation" issued by the former General Administration of Food and Drug Administration in December 2017 (No. 126 of THE Food and Drug Administration (2017) ) shall be repealed at the same time.. In order to encourage the research and creation of drugs with obvious clinical advantages, this procedure shall be formulated in accordance with the relevant provisions of the Drug Administration Law of the People's Republic of China, the Chinese Medicine Law of the People's Republic of China, the Law on Vaccine Administration of the People's Republic of China, the Regulations on the Implementation of the Drug Administration Law of the People's Republic of China, and the Measures for the Administration of Drug Registration.
. 1. The scope of application and applicable conditions
(1) the scope of application of the drug during clinical trials
, for the prevention and treatment of serious life-threatening or seriously affecting the quality of life of diseases and there is no effective means of prevention and treatment or compared with existing treatment means have sufficient evidence to have significant clinical advantages of innovative drugs or improved new drugs, the applicant may apply for the application of breakthrough therapeutic drug procedures before the phase III clinical trial.
(2) During the clinical trial of the drug
applicable conditions, the application for the application of the procedure for breakthrough therapeutic drugs shall also meet the following conditions:
1. For the prevention and treatment of diseases that seriously endanger life or seriously affect the quality of life. Serious life-threatening refers to the serious ness of the disease, irrecancure or irreversible development, significantly shorten life or lead to the death of patients, serious impact on the quality of life refers to the development of the disease seriously affect semostally daily physiological function, if not effective treatment will lead to disability, important physical and social function saucy, etc.
2. Where there is no effective means of prevention and treatment, the drug can provide an effective means of prevention and treatment, or the drug has a clear clinical advantage over existing treatment methods, i.e. single-use or in combination with one or more other drugs, with significant improvement seines at one or more clinical endpoints. This includes any of the following:
(1) there is no effective cure, the drug has significant clinical efficacy in important clinical outcomes compared to placebo or historical control of good evidence (e.g., the drug significantly improves the efficacy of the drug compared to placebo or historical control, or prolongs the patient's survival).
(2) the drug has a more significant or important therapeutic effect than existing treatments (e.g. the drug can be completely answered, while the existing treatment can only obtain a partial response; or the drug can significantly improve the response rate compared to existing treatments, which is of significant clinical significance).
(3) the combination of the drug and existing treatments with existing treatments has a more significant or more important effect than the historical comparison of existing treatments or good evidence.
(4) the available treatment can only treat the symptoms of the disease, and the drug can treat the cause and has significant clinical effects, can reverse or inhibit the development of the disease, and may bring sustained clinical benefits, to avoid the development to seriously endanger life or significantly affect the quality of life consequences.
(5) is comparable in efficacy to the current irreplaceable treatment, but the drug has significant safety advantages, and the drug is expected to replace existing treatments or make important additions to existing treatments.
available treatment means a drug approved in the territory for the treatment of the same disease, or a standard treatment (combination treatment of drugs, etc.). In general, these treatments should be the current standard treatment. Drugs subject to conditional approval for listing are not used as an existing treatment until clinical benefits have been proven.
clinicalendpoints usually refer to endpoints associated with disease occurrence, development, death, and function, and can also include proven alternative endpoints, alternative endpoints that may predict clinical benefits, intermediate clinical endpoints, safety endpoints, etc. When applying for a breakthrough therapeutic drug procedure, the applicant shall provide supporting evidence of the proposed end point.
.2, the work procedure
(i) application. During a clinical trial of a drug, the applicant shall fully assess the scope of application and conditions of the drug before proposing the application of the breakthrough therapeutic drug procedure, and may submit an application for the breakthrough therapeutic drug procedure to the Drug Review Center (Annex 1) on the website of the Drug Review Center of the State Drug Administration (hereinafter referred to as the Drug Review Center) to explain the variety information and the reasons for its inclusion.
has conducted clinical trials of multiple indications (or functional treatment) drugs as the same drug, and applicants should submit applications for the appropriate breakthrough therapeutic drug procedures separately according to different indications.
(ii) audit. The drug review center shall, in accordance with the indications (or functional treatment) formulated by the species, examine the application submitted by the applicant for the breakthrough therapeutic drug procedure, and, if necessary, organize an expert advisory committee to demonstrate.
Drug Trial Center shall, within 45 days after receiving the application, give feedback on the results of the examination to the applicant. If, due to the characteristics of the variety, it is necessary to extend the time limit for examination, the extended time limit shall not exceed one-half of the original examination time limit, and after approval by the person in charge of the drug review center, the project management personnel shall inform the applicant of the time limit and the reasons for the extension.
(iii) publicnotice included. The Drug Review Center shall make public the specific information and reasons for the varieties to be included in the breakthrough treatment drug procedure, including the name of the drug, the applicant, the proposed indications (or functional treatment), the date of application, the reasons for inclusion, etc. No objection within 5 days of publicity shall be incorporated into the breakthrough therapeutic drug procedure; if any objection to the publicity of the variety is raised, it shall submit written opinions and explain the reasons to the drug review center within 5 days (Annex 2); and the drug review center shall, within 15 days, organize a further argument and make a decision and notify the relevant parties.
before including the breakthrough therapeutic drug procedure, the applicant may apply for withdrawal and state the reasons in writing.
(iv) guidance for the development of clinical trials. The Center communicates, strengthens guidance and promotes drug development, through the priority allocation of drug allocation resources that are incorporated into breakthrough therapeutic drug programs. After preparing for work, the applicant submits an application for communication with the Drug Review Center. Communication during
drug clinical trials includes first communication, meetings due to major safety issues/major technical issues, critical stage meetings of drug clinical trials, and general technical issues consultation, which are prioritized by the Drug Review Center.
1. First communication. Within 6 months of being included in the breakthrough therapeutic drug program, the applicant may submit an initial communication application in accordance with the Class I Meeting and submit the questions to be discussed (Annex 3) and related supporting materials, including the clinical, pharmacological and pharmaceutical research and development of the drug, the communication plan with the Pharmaceutical Review Center during clinical trials, the phased research data submission plan, the drug listing application and so on. After the Drug Review Center and the applicant have agreed on the follow-up communication plan and the phased research material submission plan, the applicant shall submit a follow-up communication application in accordance with the plan.
first form of communication includes face-to-face meetings, video conferences, conference calls, or written responses. According to the progress of drug development, if the applicant does not apply for the first communication within 6 months, he or she may submit the first communication to discuss the issue in the application for the key stage of the follow-up drug clinical trial.
2. Key Stages of Drug Clinical Trials. Applicants may submit a Class II meeting application to the Drug Review Center at the critical stage of the drug clinical trial (phase II clinical trial end/PHASE III clinical trial start-up, etc.), may submit phased research data, the drug review center shall arrange relevant reviewers to communicate and communicate according to the consultation questions raised by the applicant, and provide comments or suggestions on the next research program and feedback to the applicant based on the existing research data.
(v) termination proceedings. For drug clinical trials incorporated into the breakthrough therapeutic drug program, the applicant shall promptly submit the termination procedure to the drug review center if he finds that he or she no longer meets the inclusion criteria. If the drug review center finds that it no longer meets the conditions for inclusion, it shall inform the applicant that the applicant may submit a written statement to the drug review center within 10 days, and the drug review center shall organize the demonstration and notify the applicant within 30 days after the decision has been made. If the applicant fails to submit a written statement to the drug review center within 10 days, or if the decision is proved to be ineligible for inclusion, the drug review center shall terminate the breakthrough therapeutic drug procedure of the variety in time.
find seis pedagogical seis i.e. the drug center will terminate the breakthrough therapeutic drug program:
. 1. The new clinical trial data no longer show a clear clinical advantage over the existing treatment methods;
2. The clinical trial of the drug has been terminated due to related major safety issues, etc.;
3. Other cases in which the procedure should be terminated.
the drug review center publicly included a list of varieties of breakthrough therapeutic drug procedures, updated the status information of the varieties (including the inclusion and termination information), timely included the new inclusion of the program varieties, and identified the varieties of termination procedures.
. 3. Work Requirements
(i) The Drug Review Center shall maintain communication and communication with applicants in the research and development process in accordance with the relevant provisions of the Measures for the Administration of Communication and Communication of Drug Research and Technology Review and the General Technical Advisory And Management Code for Drug Registration Review.
(2) The drug review center shall, in the course of communicating with the applicant and examining the research materials of the phase, examine the qualification of the breakthrough therapeutic drug procedure, and shall terminate the situation of terminating the breakthrough treatment drug procedure in a timely manner.
(3) For the varieties of drugs that have terminated the breakthrough treatment drug program, the drug review center shall no longer prioritize relevant communication and communication, and the time limit for communication and communication shall be implemented in accordance with the relevant requirements of the Measures for the Administration of Communication and Communication between Drug Research and Technology Review and the General Technical Advisory Management Code for Drug Registration review.
(4) For the varieties included in the breakthrough treatment drug program, the applicant may also apply for conditional approval and priority review and approval when applying for a drug listing license if the applicant has assessed that it meets the relevant conditions.
the period specified in this procedure shall be calculated on a working day.
this working procedure shall come into effect as of the date of publication.In order to encourage clinical value-oriented drug innovation and accelerate the listing of clinically urgently needed drugs with outstanding clinical value, the
has formulated this working procedure in accordance with the relevant provisions of the Drug Administration Law of the People's Republic of China, the Law of the People's Republic of China on Chinese Medicine, the Law of the People's Republic of China on Vaccine Administration, the Regulations on the Implementation of the Drug Administration Law of the People's Republic of China, and the Measures for the Administration of Drug Registration.
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the conditions of a drug that meets the conditions and conditions for approval of the conditions set out in the technical guidelines for the approval of the drug subjecttoual conditions, the applicant may, during the drug clinical trial, submit an application for conditional approval to the Drug Review Center of the State Drug Administration (hereinafter referred to as the Drug Review Center). Among them:
1. Urgently needed medicines in public health are put forward by the relevant departments such as the National Health and Health Administration.
2. Vaccines urgently needed for major public health emergencies shall be preventive vaccines for major public health emergencies (Level II) or especially major public health emergencies (level I) related diseases identified in accordance with the Emergency Regulations on Public Health Emergencies, national emergency for public health emergencies, etc.
Ii, the work procedure
(I) early communication and communication applications (Class II meetings). Applicants are encouraged to communicate with the Drug Review Center, as required by the relevant technical guidelines, on the approved clinical research plan, the selection of key clinical trial design and efficacy indicators, the prerequisites for other conditional approval, the design and implementation plan of the post-market clinical trial, etc. during the clinical trial of the drug.
(ii) communication application (Class II meeting) prior to listing application. If the application for conditional approval for listing is submitted, the applicant shall communicate with the drug review center on the conditions for approval of listing and the research work to continue to be completed after listing, and those who intend to apply for priority review and approval may propose communication and communication. Those who have been included in the breakthrough therapeutic drug program may apply for a class I meeting.
(3) submit a conditional application for approval of listing. If the communication and evaluation confirms that the requirements for approval of the conditionalconditions are initially met, the applicant may, at the same time as submitting the application for a drug listing license, submit an application for approval of the drug conditionality to the drug examination center (see annex for the application form) and submit supporting information in accordance with the requirements of the relevant technical guidelines. Where an application is for priority review and approval, an application may be made together.
(iv) review and approval. If the review is approved and the drug is approved for listing, a certificate of drug registration shall be issued, and the validity period of the certificate of approval of the drug registration shall be specified, the research work to be continued to be completed after listing and the time limit for completion shall be specified. The validity of the drug registration certificate shall be determined by the drug review center after communication with the applicant during the review, in accordance with the time limit for the completion of the post-marketing research work.
based on all the filing information submitted by the applicant, if the technical review found that the requirements for approval of the listing of the list are not met by technical review, the drug review center shall terminate the procedure for the review and approval of the application for listing of the drug with conditional approval, make the evaluation conclusion of the application for approval of the listing with conditions, and inform the applicant through the window of the applicant of the drug review center website to explain the reasons. Applicants may re-file in accordance with normal procedures after completing the corresponding study. If the applicant has any objection to the conclusion of the review, he may submit it in accordance with the relevant procedures for resolving the objection to the conclusion of the drug registration review. After the examination and approval of the application for drug registration, the applicant may file an administrative review or administrative action in accordance with the law if he objects to the decision on the administrative license.
(v) after listing requirements. For drugs approved for listing on the conditions, the holder of the drug listing license shall take appropriate risk management measures after the drug is listed and complete relevant research such as clinical trials of drugs within the prescribed time limit, so as to declare the supplementary application.
the post-marketing research submitted by the holder of the drug listing license proves that the benefits outweigh the risks, and the review is approved, the drug registration certificate valid for 5 years shall be issued, and the validity period of the certificate shall be from the date of approval of the listing application.
if the post-marketing study submitted by the holder of the drug market license shall not prove that the benefits outweigh the risks, the drug review center shall make the non-approved review conclusion and the State Drug Administration shall cancel its drug registration certificate in accordance with the procedure.
the holder of a drug listing license fails to complete the study and submit a supplementary application as required within the time limit, the State Drug Administration shall cancel his drug registration certificate in accordance with the procedures.
. 3. Work requirements
(1) communication and communication in the process of approving the listing application on conditions, and shall be implemented in accordance with the relevant provisions of the Measures for the Administration of Communication and Communication between Drug Research and Development and Technical Review.
(ii) the applicant is submitting the annex.