药物研发与技术审评沟通交流管理办法-EN

Communication for Drug R&D Activities and

Technical Review

(Draft for Comment)

Chapter I General Provisions

Article 1 This regulation is formulated for the purpose of good performance of communication and standardization of the communication between the applicants and the Center for Drug Evaluation of NMPA (hereinafter referred to as CDE), by following the principles of the Pharmaceutical Administration Law of the People's Republic of China, and Measures for the Administration of Drug Registration.

Article 2 The communication, described in this regulation, is defined as the consultation and discussion applied by the applicants during the drug research and development process, through negotiation between the project management staff of CDE (hereinafter referred to as the “Project Manager”) and the drug registration specialist designated by the applicant, and approved by the review team of CDE, discussing the key technical issues that are not covered by the current drug R&D and review guidelines.

Article 3 The forms of communication include: face-to-face

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meeting, video conference, teleconference and written correspondence. Applicants are encouraged to communicate with CDE through teleconference. The proposal, consultation and conduct of the communication, as well as the preparation, convening, recording and minutes of relevant meetings, shall comply with this regulation.

Article 4 The communication meetings stipulated in this regulation shall be applicable to the communication and consultation for the innovative drugs, modified new drugs, biosimilar drugs, Chinese herbal medicine compound preparation based on traditional classic prescription, drugs with the same name and prescription, complex generic drugs, and equivalency assessment drugs during their R&D process and registration applications.

Article 5 Communication is an interaction process dealing with the technical issues between the applicant and the review team, during which both parties may fully present their respective viewpoints with regard to such issues.

Chapter II Types of Communication Meetings

Article 6 Communication Meetings are divided into Class I, Class II and Class III meetings, at which the communication takes place in respect to major issues at key stages.

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(I) Class I meeting is defined as the meeting held on the

purpose to address the major safety issues encountered during the clinical trials of drugs, and the major technical issues in the R&D process of the breakthrough therapeutic drugs, or held in other prescribed situations.

(II) Class II meeting is defined as the meeting held at the key

stages of drug R&D process, which mainly include the following situations: 1.

Pre-Clinical Trial Application meeting. To address major technical issues before the first submission of the clinical trial application, the following issues can be discussed, including but not limited to: whether the available research data supports the proposed clinical trial; whether the risk of clinical trial subjects is controllable. The communication meeting materials prepared by the applicant shall include complete information on the clinical trial protocols or drafts, existing pharmaceutical and non-clinical study data, and other research data. For the clinical trial applications of the first global applications of the drugs with new mechanism and new structure, the applicant shall initiate the communication with CDE, and the technical requirements on the registration shall be established clearly. 2.

End of Phase II clinical trial of drugs/Phase III pre-clinical trial meeting. To address major technical issues encountered

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at the end of Phase II clinical trial and prior to the initiation of pivotal Phase III clinical trial, the following issues can be discussed, including but not limited to: whether the available research data can fully support the proposed Phase III clinical trial; make assessment on Phase III clinical trial protocol. 3.

Pre-meeting for drug marketing authorization. To explore whether the available research data meets the technical requirements for the application for drug marketing authorization, the following issues can be discussed, including but not limited to: whether the available research data supports the technical requirements for the application for drug marketing authorization. The applicant for conditional approval and/or for priority review approval procedures shall communicate with the CDE before submitting the application for drug marketing authorization to NMPA. 4.

Risk assessment and control meeting. This meeting is to have a discussion before NDA approval on the adequacy and controllability of the post-marketing risk control in order to assess and control the post-marketing risk. 5.

Other circumstances of Class II meetings as prescribed. I and Class II meetings.

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(III) Class III meeting is defined as the meetings other than Class

Article 7 Applicants who have fallen into one of the following circumstances may propose the corresponding communication application based on the proposed studies or submissions in accordance with the provisions of the three classes of meetings mentioned above.

(I) For clinical trial application of adding new indication, the

applicant shall carry out the research on the basis of available data in combination with the characteristics of the new indication, and make communication with CDE if necessary.

(II) For the key technical issues found during the R&D process

of drugs for urgent clinical needs or treatment of rare diseases, the applicant may make the communication application.

(III) For the major R&D issues in the complex generic drugs and

equivalency assessment or re-assessment drugs (e.g. selection of the reference preparation, evaluation criteria for bioequivalence, etc.), the applicant may make the communication application.

(IV) For the protocol designed for the complicated important

non-clinical studies (e.g. carcinogenicity studies), the applicant may make the communication application. (V) Where there is technical disputation in the review process

after the applicant has received the inquiry consultation and

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supplementary notification, the applicant may make the communication application if the applicant still has any difference regarding the comprehensive assessment results. (VI) Application for communications can be made in the R&D

process of drugs on the frontier technology field.

Chapter III Proposal and Discussion of Communication

Meetings

Article 8 The convening of a communication meeting shall meet the following basic conditions:

(I) The “Application Form for Communication Meeting”

(Annex 1) and “Communication Meeting Materials” (Annex 2) submitted shall comply with the requirements of the regulation;

(II) \"Communication Meetings Materials” and the \"Application

Form for Communication Meetings\" shall be submitted at the same time;

(III) The professional background of personnel participating in

the communication meeting shall be qualified for the discussion on professional issues. Article 9

Where the above communication requirements are

met, the applicant shall submit the Application Form for Communication Meeting and Communication Meetings

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Materials through the “window of applicant” of the website of CDE, specifying the type of communication at application. Article 10 Within 2 days of receiving the “Application Form for Communication Meeting”, the Project Manager shall complete the preliminary review according to requirements above. Where the materials are found not complete or to have fallen into other cases of nonconformity, the application shall be ended. Those meeting the requirements shall be further submitted to relevant professional review team.

Within 18 days after the application, the review team shall determine how to carry out the communication: communication meeting (face-to-face meeting, video conference, teleconference) or written feedback. If the review team finds that any data is incomplete or inconsistent, the application shall be terminated directly.

Article 11 Within 20 days after the application, the Project Manager will notify the applicant the conclusion confirmed by the review team.

For the communication meeting application approved, the Project Manager will notify the meeting agenda to the applicant through the “window of applicant” within 5 days after the confirmation of meeting date, including the date, place, matters needing attention and materials to be further discussed at the meeting.

Article 12 Communication meeting application may not be

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approved for the following circumstances:

(I) Additional data shall be provided before satisfying the

communication requirements for the issues to be discussed; (II) The professional background of attendees is not qualified

for the discussion of the technical issues and not satisfactory to the need for communication;

(III) Other circumstances that do not guarantee the effective

convening of the meeting.

If the communication meeting cannot be convened, the Project Manager shall provide the specific reasons through the “window of applicant”. After finishing relevant works, the applicant can make a new communication application.

Article 13 If the communication meeting is approved, in general, Class I meeting will be held within 30 days after the application, Class II meeting will be held within 60 days after the application, and Class III meeting, within 75 days after the application.

If the communication meeting is confirmed not to be held, the feedback shall be completed within the above-mentioned time limit according to the meeting type, in principle.

Chapter IV Preparation for Communication Meetings

Article 14 The applicant shall submit the electronic version of

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Communication Meeting Materials in accordance with the requirements of the “Communication Meeting Materials” through the \"Window of Applicant\".

Article 15 To ensure the quality and efficiency of communication meetings, the drug registration specialist shall make comprehensive discussion with Project Manager before the meeting, and confirm the date, time, place and agenda of the meeting.

Chapter V Convening of Communication Meetings

Article 16 The communication meeting will be chaired by the CDE staff, and conducted according to the pre-determined meeting agenda. Discussion shall be made on proposed issues put forward before the meeting. In principle, it is not within the scope of communication to raise new meeting materials, generate divergent issues and to temporarily add new issues. In general, the communication meeting duration shall be within 45 minutes, but not exceed 60 minutes.

Article 17 The minutes of meeting shall be prepared in accordance with the \"Template of Communication Meeting Minutes\" (Annex 3). Where both parties have reached an agreement, viewpoints in common shall be specified. If the parties fail to reach an agreement, their viewpoints shall be stated

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respectively. The applicant is encouraged to make minutes of meeting on the spot, for the purpose of which the applicant can make a draft of the minutes before the meeting on the basis of the preliminary feedback from CDE and make it clear after discussion. If the minutes cannot be made on the spot for special reasons, the applicant shall generally submit the draft of minutes within one week after the meeting is completed. Minutes of meeting shall be finalized within 30 days upon the completion of the meeting. The Project Manager shall upload the minutes within 2 days upon finalization, to the communication system which can be accessed by the applicant through the “Window of Applicant”. Meeting minutes shall be archived as an important document. Article 18 If necessary, CDE will make audio or video recordings of whole procedure of the meeting, and archive them as working files for future reference. The applicant and other attendees are not allowed to make any audio, video or photo recordings without permission. Where the applicant’s trade secrets are involved, CDE shall keep such trade secrets confidential in accordance with applicable laws.

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Chapter VI Postponement or Cancellation of

Communication Meetings

Article 19 The meeting will be postponed if any of the following circumstances occurs:

(I) The communication conditions are met but additional

information shall be supplemented;

(II) The review team considers that there are other important

issues beyond the meeting topic that need further discussion; (III) There are too many meeting materials for the review team

to review in a limited period;

(IV) The important attendees cannot attend the meeting on time; (V) Other force majeure factors.

In general, the applicant shall be notified of the decision to postpone a meeting, at least 5 days prior to the meeting. The postponed meeting will be discussed by the Project Manager and the drug registration specialist. In general, the delay time shall not exceed 2 months. It will be considered that the meeting cannot be held if the delay time is more than 2 months due to the applicant, in which case the applicant is required to submit a new communication application after supplementing additional materials.

Article 20 A meeting will be cancelled if any of the following situations occurs:

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(I) The meeting materials are not submitted within the

specified date;

(II) The submitted meeting materials do not meet the

requirements of this regulation;

(III) The applicant makes the proposal of canceling the meeting

which is approved by CDE;

(IV) The issue from the applicant has been resolved or has been

given written correspondence.

In general, the decision to cancel a meeting shall be informed to the applicant 5 days prior to the meeting. After cancellation of the meeting, the applicant may submit a separate communication application according to this regulation.

Chapter VII

Supplementary Provisions

Article 21 For the verification or consultation of general technical issues, the applicant may communicate with the Project Manager through the general technical issue consultation platform in \"Window of Applicant\other means. Consultations on general technical issues will not include the key technical issues in drug R&D and technical review processes.

Article 22 When making submission of the drug registration dossier, the applicant shall appoint 1 or 2 drug registration

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specialists, and provide the specific information of the drug registration specialist such as the name and telephone number. The drug registration specialist shall be responsible for drug registration. The applicant shall make communication with CDE through the drug registration specialist, and the Project Manager shall only contact the drug registration specialist designated by the applicant. If there is any change of the drug registration specialist, the applicant shall make updates through the “Window of Applicant” in a timely manner.

Article 23 During the review process, CDE may make a proposal on communication as required, which will be discussed by Project Manager with the drug registration specialist to determine the, time, agenda, and information requirements for the communication meeting.

Article 24 The meeting materials used for communication shall be included in the applied registration documents (which may be compiled into an individual volume) as the basis for review. Important meeting materials prior to the submission of a drug registration application, e.g. Communication Meetings Materials, Application Form for Communication Meeting and meeting minutes, should be submitted by incorporating into the dossiers. The meeting materials generated during the review should be included into the dossiers by CDE.

Article 25 CDE staff shall strictly follow this regulation, and

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must not contact the applicant privately in any way other than those provided in this regulation. The special case shall be approved by CDE.

Article 26 This regulation shall come into force as of the date of promulgation.

Annexes: 1. 2. 3.

Application Form for Communication Meeting Communication Meeting Materials

Template of Communication Meeting Minutes

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Annex 1

Application Form for Communication Meeting

I. Basic information of drug research and development 1. Applicant 2. Drug name

3. Acceptance number (if available)

4. Chemical name and structure (or prescription, for Chinese Traditional Medicine)

5. Proposed indications (or major functions)

6. Dosage form, administration route and regimen (medication frequency and treatment cycle)

7. Drug R&D strategies, including drug R&D background information, drug development plans, brief description of the R&D process, key events, and current development status. II. Specific contents of meeting application 1. Meeting types: Class I, Class II, or Class III.

2. Classification of meeting: such as Pre-Clinical trial application meeting, End of Phase II clinical trial/Phase III pre-clinical trial meeting, Pre-meeting for drug marketing authorization or risk evaluation and control meeting. 3. Meeting forms: face-to-face meeting, video conference,

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teleconference or written correspondences. 4. Meeting objective: brief description.

5. Proposed meeting date and time: please provide 3 alternatives. 6. Proposed meeting agenda: including estimated duration for each topic to be discussed (in general, the discussion duration of all topics should be controlled within 60 minutes.) 7. List of attendees of applicant: the list shall set forth the names of attendees, including the positions, job contents and work units. If the applicant plans to invite experts and interpreters to attend the meeting, they shall also be involved in the list. 8. List of proposed issues under discussion: it is recommended that the applicant shall make the list of issues by discipline, including but not limited to the issues of the pharmaceutical, pharmacology & toxicology, and clinical practice. Each issue should include a brief description of background, the purpose of proposed issues and the applicant’s opinions of issues. In general, the number of issues to be discussed at a meeting shall not exceed 10.

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Annex 2

Communication Meeting Materials

1. List of issues under discussion: a list of issues that applicant has finalized. It is recommended that the applicant shall make the list of issues by discipline, including but not limited to the issues of the pharmaceutical, pharmacology & toxicology, and clinical practice. Each issue shall include a brief description of background and the purpose of issues proposed.

2. Supporting data summary: summary of supporting data by discipline and the order of issues.

In terms of the summary of supporting data, relevant studies, results and conclusions shall be explained by data. Taking end of Phase II clinical trial meeting as an example, the clinical professional summary shall include the following: (1) a brief summary of completed clinical trials, including data, results and conclusions. Important dose-effect relationship information shall also be included. In general, a complete clinical study report does not need to be provided; (2) a detailed introduction of the proposed Phase III clinical trial protocol to confirm the main characteristics of clinical trials, such as clinical trial subject population, the key inclusion and exclusion criteria, clinical trial

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design (e.g., randomization, blinding, control selection, justification of non-inferiority threshold if non-inferiority trial used), dose selection, primary and secondary efficacy endpoints, and primary analysis methods (including planned interim analysis, characteristics of adaptation studies, and major safety concerns).

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Annex 3

Template of Communication Meeting Minutes

Meeting types: Class I, Class II, or Class III.

Classification of meeting: such as Pre-clinical trial application meeting, End of Phase II clinical trial/Phase III pre-clinical trial meeting, Pre-meeting for drug marketing authorization or risk evaluation and control meeting. Date and time of the meeting: Meeting place:

Acceptance number (if available): Drug Name:

Proposed indications (or major functions): Applicant: Chairman: Recorder:

Attendees: a list of all attendees of the applicant and CDE. Text:

1. Purpose of the meeting: 2. Meeting background:

3. Issues discussed at the meeting and results:

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(1) Issue 1: XXXXXXXXX Do both sides reach consensus? □ Yes.

Common opinion: XXXXXXXXX □ No.

Applicant's comments: CDE's comments: (2) Issue 2: XXXXXXXXX …

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