CDE's new regulations speed up the launch of innovative drugs!

Detailed work requirements for each link

On July 1, 2020, the newly revised "Measures for the Administration of Drug Registration" was officially implemented, opening a new situation for the optimization of the work process of drug review and approval in China, and the standardization and strengthening of drug registration management
.

Learning from international regulatory experience, the newly revised "Drug Registration Management Measures" added the chapter "Drug Registration Procedures for Accelerated Marketing", which has attracted widespread attention.
There are four accelerated channels for breakthrough therapy drugs, conditional approval, priority review and approval, and special approval.

Among them, "breakthrough therapy drugs" and "conditional approvals" are undoubtedly the two accelerated paths that have attracted the most attention from the industry
.

The newly revised "Measures for the Administration of Drug Registration" clarifies that during the clinical trial of drugs, it is used to prevent and treat diseases that are seriously life-threatening or seriously affecting the quality of life, and there is no effective prevention and treatment method or there is sufficient evidence compared with the existing treatment methods to show obvious clinical symptoms.

The "Working Procedures" formulated this time are mainly divided into three parts: the scope of application and review time limit, work procedures, and work requirements, and detailed work requirements are formulated for each link of early communication, acceptance, and review of registration applications
.

For example, the communication link is divided into two categories: key clinical trial related and pre-NDA, and the research materials and points of attention that applicants should submit in different time periods of new drug research and development are carried out.

The relevant person in charge of CDE has publicly stated that the general idea of ​​the breakthrough therapy drug work program is in line with international standards, and reference to foreign Fast Track (Fast Track) and Breakthrough Therapy (Breakthrough Therapy) when designing, for research drugs with obvious clinical advantages, in In the stage of drug clinical trials, support policies such as technical guidance and whole-process communication are given to speed up the process of drug development and marketing
.

From the relevant requirements of the "Working Procedures", we can see that CDE strengthens the communication of the whole process, improves the efficiency of completing clinical trials, and focuses on supporting and accelerating the specific practice of high-value new drug research and development

As CDE stated in the drafting instructions, the original intention of formulating this working procedure is to encourage the research and creation of new drugs, to meet the needs of clinical medication, to summarize and transform the work experience of emergency response review in a timely manner, and to speed up the review of innovative drugs
.

From the perspective of the industry, this working procedure transforms, consolidates and expands the previous achievements and valuable experience in the form of a system, which will more effectively help applicants to promote the clinical research and development of drugs and accelerate the pace of listing related innovative drugs

90 innovative drugs were included in the list

On July 8, 2020, the State Food and Drug Administration officially released the "Breakthrough Therapy Drug Review Work Procedures (Trial)", which includes key issues such as the scope of application, application, review and certification, public announcement, and termination procedures of the breakthrough therapy drug work process.

Specific requirements are made for the content

  According to other statistics, 41 drugs have been granted breakthrough therapy designation in 2021
.

From the perspective of disease treatment, the field of oncology is undoubtedly a fertile ground for the emergence of breakthrough therapeutic drugs, accounting for 54% (22/41) last year.

  From the perspective of companies, Hengrui, Johnson & Johnson and Takeda are among the top three drug companies that have obtained CDE breakthrough therapy drug designation
.

Among them, Johnson & Johnson is involved in viral infection drugs, including JNJ-56136379, JNJ-73763989 and JNJ-53718678; Hengrui's SHR0302, SHR3680 and SHR6390 are involved in three adaptations of atopic dermatitis, prostate cancer and breast cancer respectively Takeda's Maribavir, TAK-935, and TAK-994 are involved in three major therapeutic areas of cytomegalovirus, pediatric epilepsy and narcolepsy respectively

  The industry generally believes that with the announcement and clarification of the "Working Procedures", breakthrough therapy drugs are expected to further shorten their listing process
.
However, some experts in the industry reminded that the primary value brought by breakthrough therapy drugs to relevant pharmaceutical companies in drug research and development is more opportunities for communication with regulatory agencies, not a promise to be approved for marketing.
Pharmaceutical companies need to carefully grasp this seeking technology Great way to support
.
With the continuous progress of science and technology and drug research and development, the standard threshold for the identification of breakthrough therapeutic drugs in the future will inevitably become higher and higher.
The clinical value of drugs will always be the first factor considered by regulatory agencies, and products can only achieve real clinical efficacy.
Breakthrough, Fang is eligible to compete in this golden track of breakthrough therapeutic drugs
.

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The Center for Drug Evaluation Accelerates the Review of Innovative Drug Marketing Applications (Trial)

(Draft for comments)

  In order to encourage the research and creation of new drugs, meet the needs of clinical drug use, and speed up the review and approval of innovative drug varieties, this working procedure is formulated
.

  1.
Scope of application and review time limit

  (1) Scope of varieties: applicable to innovative drugs included in the breakthrough therapy drug program
.

  (2) Research and development stage: It is applicable to the applicant who has completed the exploratory clinical trial and has the conditions to carry out the pivotal clinical trial until it is approved for marketing
.
This procedure does not require applicants to apply, and the innovative drug varieties included in the breakthrough therapy drug procedure can automatically carry out follow-up communication and review and approval according to this procedure
.

  (3) Time limit requirements: The time limit for communication is 30 days, and the time limit for variety review and priority review is 130 days
.

  2.
Working procedure

  (1) Communication

  For varieties that meet the scope of this procedure, applicants can apply for communication according to the Class I meeting (30 days)
.

  1.
Communication about pivotal clinical trials

  After completing the preliminary exploratory clinical trial, the applicant can submit an application for communication before and during the pivotal clinical trial, clearly put forward the key technical issues affecting the drug application and relevant supporting materials, and submit the phased registration application format requirements.
research data
.

  The Center for Drug Evaluation will set up a review team based on the specific variety, grouping of indications, review task characteristics, and personnel conflicts of interest
.
The review team is responsible for the entire process of communication before the application of the product to the technical review after the acceptance.
The team generally includes reviewers, compliance reviewers, acceptors and project managers
.

  At this stage, the Center for Drug Evaluation and the applicant discussed and reached consensus on the follow-up communication plan, the submission plan for phased research data, and the submission plan for drug marketing authorization applications
.
The applicant should carry out the follow-up work according to the plan, and the Center for Drug Evaluation will continue to connect and guide the applicant
.
At the same time, the acceptance personnel of the Drug Evaluation Center can intervene in advance to guide the applicant to organize the application materials as required
.

  2.
Communication before marketing authorization application (pre-NDA)

  Before submitting an application for drug marketing authorization, an applicant may submit an application for communication, clearly state the issues to be discussed and relevant supporting materials, and submit research materials that meet the requirements of the format and content of the registration application materials
.
This type of communication application can be applied after a single major or multiple majors have completed the preparation of listing application materials
.

  According to the consultation questions raised by the applicant, the Center for Drug Evaluation will arrange the review team to communicate and conduct preliminary review of the research data
.
The Center for Drug Evaluation can report back to the applicant on the problems existing in the current application materials.
After the applicant has further supplemented and improved it, he can submit a communication and exchange application for rolling supplementary materials
.

  In addition to relevant technical issues, the review team should initially review the production process information sheet, quality standards, instructions, and label samples and other approval documents
.
The applicant should complete the corresponding revisions according to the review requirements before applying for listing, and provide the revised appendix of the approval document when applying
.

  Depending on the specific circumstances of the drug development, the applicant may agree with the Center for Drug Evaluation on the plan to submit further information (such as longer-term efficacy and safety data, etc.
) after the submission of the marketing authorization application
.

  (2) Verification and inspection

  Applicants should prepare a complete set of application materials CD-ROM for registration verification and inspection (including research and development information table, production information table, on-site master file list, clinical trial research information table and clinical trial information summary table) before the official application for listing.
And quality standards, production process (manufacturing and verification procedures)
.

  In principle, the registration verification and inspection work for such varieties shall be prioritized in accordance with the priority review and the relevant requirements of the "Startup Procedures for Drug Registration Verification Inspection (Trial)"
.

  Registration inspection: Applicants are encouraged to submit registration inspection to the drug inspection agency before the official application for marketing
.
If the applicant does not submit a drug pre-registration inspection before acceptance, the Center for Drug Evaluation will issue a registration inspection notice to the applicant and inform the drug inspection agency upon acceptance
.

  Registration verification: All review majors and compliance majors should complete the marking of variety factors and compliance factors of R&D and production entities within 7 days after the arrival of the registration application task, and complete the electronic push of the start-up registration verification task within 10 days
.

  (3) Acceptance and assignment of tasks

  The acceptance and project managers of the Center for Drug Evaluation should intervene in advance, participate in and guide the preparation of the applicant's application materials during the pre-NDA communication and exchange stage, and ensure that the acceptance problems are resolved before the application, and the applicant can submit the application materials to be accepted
.
For the approval of generic names, refer to the priority review process
.

  The project manager will follow up the variety situation throughout the process, coordinate and communicate with each link, and assign tasks as soon as possible after the variety is accepted, and make special marks in the review system to ensure the smooth progress of the related variety acceptance and review work
.

  (4) Professional review

  The head of the professional review shall assign review tasks according to the review team members determined by the Pre-NDA communication
.
Before starting the review and approval, professional reviewers should re-confirm their mistaken conflicts of interest on the technical review system, and those who have no conflicts of interest should sign a non-conflict-of-interest statement, and then start the review work
.

  According to the needs of the technical review and the consensus reached at the communication meeting, the professional chief reviewer may, in accordance with the relevant requirements of the priority review work, put forward the requirements for receiving rolling data, and handle the data reception and archiving work after reviewing and agreeing according to the process
.

  During the professional review process, if the professional technical committee of the professional department needs to hold an expert consultation meeting, the professional review department may request to hold a meeting through the internal request of the center under the condition that the professional time limit is guaranteed
.
The Center for Drug Evaluation will give priority to organizing an expert consultation meeting (online meetings are encouraged), which will be organized within 10 days in principle, and the specific meeting organization will be implemented in accordance with the work of the expert consultation meeting
.

  (5) Comprehensive review

  On the basis of various professional opinions, the chief reviewer will make a summary, draft a comprehensive report of the chief reviewer, create an approval document on behalf of the reviewer, upload the corresponding attachments, and submit it to the head of the chief reviewer's report department for review
.

  During the comprehensive review process, if it is necessary to hold an expert consultation meeting after discussion by the professional technical committee of the department, the comprehensive review department proposes to hold a meeting in accordance with the procedures of the expert consultation meeting.
Organized within 10 days
.

  (6) Review and issue

  After the head of the chief review report department submits the comprehensive report and the draft approval document to the center leader, the center leader will review and issue it
.

  (7) Parts sent to the bureau

  The Business Management Office will complete the production of the documents for signature within 3 working days, and send them to the National Bureau for approval on time
.

  3.
Job requirements

  (1) The applicant should improve the awareness of the main responsibility of drug research and development.
When submitting an application for communication and exchange, the meeting materials and questions should be matched with the current research and development stage, and supporting research materials should be provided to improve the efficiency and quality of communication
.

  (2) The project manager of the Center for Drug Evaluation shall assist the evaluation team to strengthen the coordination and supervision of varieties
.

  (3) The evaluation team of the Center for Drug Evaluation shall strengthen communication, solve existing technical problems in a timely manner, and ensure that the evaluation work is completed within the time limit
.