Note! There are significant changes to the CDE submission of supplementary information!!!

Annex 1: Precautions for supplementary information on preparations

In order to avoid delaying the review progress of the drug registration application due to the irregular submission of supplementary information, applicants are requested to pay attention to the following matters when preparing relevant materials according to the requirements of the "Supplementary Information Notice" of our center:

1.
For registration applications accepted before January 1, 2023, supplementary information will still be replied in paper form, in triplicate
.
Applicants are requested to compile supplementary information according to the following requirements:

(1) All supplementary materials should use the national standard (quality 80g) A4 type paper, which must be completed by declaration and test and stamped
at the seam of the cover.

(2) The three sets of supplementary information submitted by the applicant shall be organized according to the current requirements and packed into a document bag, of which at least one set of originals (physical copies with seals)
shall be included.

(3) The front of the document bag should indicate: acceptance number, product name, declaration, and mark the original and copy
.
The order of the information in the document bag is: a copy of the supplementary information notice (if it involves the review of the inspection department, the inspection certificate must be submitted with the official seal of the inspection department), the information description and the annex statement (with official seal) of the "Supplementary Information Working Procedures of the Drug Evaluation Center (Trial)", the data catalog, and the technical information (listed in the order of the opinions in the "Supplementary Information Notice").

2.
For applications for registration accepted after January 1, 2023, the number of supplementary information shall be replied in electronic form as the number of copies of the declaration materials
submitted.
Applicants are requested to compile supplementary information according to the following requirements:

(1) All supplementary materials shall be submitted to our center in the form of CD-ROMs, which shall comply with the provisions of the Notice on Relevant Requirements for Electronic Declaration of
Drug Registration Applications.

(ii) The disc should be packed in the hard case of the disc and packed separately in
the file bag.
The cover page should be affixed on the disc case and file bag, and the cover information should be filled in in accordance with the Notice on Relevant Requirements for Electronic Declaration of Drug Registration Application, and the official seal
of the drug registration applicant should be affixed after printing.

(3) The electronic documents of supplementary information shall include: supplementary information notice (if it involves the review of the inspection department, the electronic information of the inspection certificate with the official seal of the inspection department shall be submitted), the submission of information description and statement (with official seal), data catalog, and technical data (arranged in the order of the opinions in the "Supplementary Information Notice"
).

3.
The time for our center to receive on-site supplementary materials is from 9:00 to 11:30 a.
m.
every Monday to Friday; Monday, Tuesday, Thursday, 13:00-16:30; The above information can also be submitted by post, please pay special attention to the following:

(1) Please submit supplementary information in strict accordance with the requirements of the "Supplementary Information Notice", and for other materials that exceed the content of the notice submitted together when sending supplementary information, in accordance with the provisions of Article 21 of the "Supplementary Information Working Procedures of the Drug Evaluation Center (Trial)", our center will not accept it, and will be destroyed in a unified manner
.

(2) In order to ensure the safety and timely delivery of mailing materials to our center, please send them by express mail as much as possible, and indicate that the business management office will receive them
.
The submission time of supplementary information is subject to the postmark, and the review task
will be initiated after receiving and confirming that it meets the relevant requirements.

(III) In order to facilitate our center's timely feedback on the receipt of materials, when mailing materials, please accurately indicate the following information in the mail: name, contact person, contact number, fax, etc
.

(4) Once the above supplementary information is officially received by our center, you can check the receipt in the progress inquiry column of our center's website, if necessary, please print it yourself, and our center will no longer send a written receipt
.

4.
If you have any doubts about the content of this precaution, you can call our center's business management office
.

Annex 2: Precautions for supplementary information of the original and auxiliary packages

In order to avoid delaying the review progress of the drug registration application due to the irregular submission of supplementary information, applicants are requested to pay attention to the following matters when preparing relevant materials according to the requirements of the "Supplementary Information Notice" of our center:

1.
All supplementary materials shall be submitted to our center in the form of CD-ROMs, the number of copies shall be the same as the number of submitted declaration materials, and the CD-ROMs shall comply with the provisions of the Notice on Relevant Requirements for Electronic Declaration of Drug Registration Applications, and the folder name of the root directory of electronic declaration materials shall be "Supplementary Information 1" and "Supplementary Information 2".
Indicates the first supplement, the second supplement
.
If the review of the preparation is related, the folder name of the root directory of the supplementary information should be accompanied by the preparation acceptance number to distinguish it
.
The file format should comply with the corresponding electronic filing requirements
.

Second, the disc should be packed into the hard case of the disc and packed separately in the
file bag.
The cover page should be affixed on the disc case and file bag, and the cover information of the API should be filled in in accordance with the Notice on the Relevant Requirements for Electronic Declaration of Drug Registration Application, and the official seal
of the drug registration applicant should be affixed after printing.

3.
The electronic documents of supplementary information shall include: supplementary information notice (if it involves the review of the inspection department, the electronic information of the inspection certificate with the official seal of the inspection department shall be submitted), the submission of information description and statement (with official seal), data catalog, and technical information (listed in the order of the opinions in the "Supplementary Information Notice"
).

4.
The time for our center to receive on-site supplementary materials is from Monday to Friday, 9:00-11:30 a.
m.
; Monday, Tuesday, Thursday, 13:00-16:30; The above information can also be submitted by post, please pay special attention to the following:

(1) Please submit supplementary information in strict accordance with the requirements of the "Supplementary Information Notice", and for other materials that exceed the content of the notice submitted together when sending supplementary information, in accordance with the provisions of Article 21 of the "Supplementary Information Working Procedures of the Drug Evaluation Center (Trial)", our center will not accept it, and will be destroyed in a unified manner
.

(2) In order to ensure the safety and timely delivery of mailing materials to our center, please send them by express mail as much as possible, and indicate that the business management office will receive them
.
The submission time of supplementary information is subject to the postmark, and the review task
will be initiated after receiving and confirming that it meets the relevant requirements.

(III) In order to facilitate our center's timely feedback on the receipt of materials, when mailing materials, please accurately indicate the following information in the mail: name, contact person, contact number, fax, etc
.

(4) Once the above supplementary information is officially received by our center, you can check the receipt in the progress inquiry column of our center's website, if necessary, please print it yourself, and our center will no longer send a written receipt
.

5.
If you have any doubts about the content of these precautions, you can call the business management office
of our center.

Annex 3 Working Procedures for Supplementary Information of the Center for Drug Evaluation (Trial)

Chapter I General Provisions

Article 1: In order to standardize the management of supplementary materials for drug registration and review, clarify the basis and requirements for supplementary materials, and improve the quality and efficiency
of supplementary materials for applicants.
This procedure
is formulated in accordance with Article 87 of the Measures for the Administration of Drug Registration.

Article 2 This procedure
shall apply to the Drug Evaluation Center of the State Medical Products Administration (hereinafter referred to as the Drug Review Center) according to the needs of the review, if the drug registration applicant (hereinafter referred to as the applicant) supplements new technical data on the basis of the original declaration materials (hereinafter referred to as the supplement), or only needs the applicant to explain the original declaration materials.

Article 3 The drug review center invites the applicant to explain or provide relevant supporting materials through the professional review inquiry before the issuance of the supplement and the supplementary information inquiry procedure after the issuance of the supplement, and actively communicates with the applicant to improve the quality and efficiency
of the supplementary information.

Article 4: The principles of
lawfulness, science, justice, fairness, timeliness, and accuracy shall be followed in the process of supplementing materials.

Chapter II: Professional Review Inquiries

Article 5 During the professional review or comprehensive review, if the professional chief reviewer or chief reviewer has doubts about the declaration materials or believes that there are problems with the content on the basis of full review, after review by the person in charge of the review department, the "professional review inquiry letter" is issued to the applicant through the website of the drug review center.
Inform the applicant of the specific content, basis and requirements of the problem, and request an explanation or written reply
within 5 working days.

During the review process, the evaluation department shall send a "professional review inquiry letter" to inform the applicant in advance of the
issues that need to be supplemented.
However, the "professional review inquiry letter" is not a formal written supplementary information notice, nor does it represent the final review decision-making opinion, and the review schedule is not suspended.

Article 6 The Drug Review Center shall inform the applicant of the following information through the "Professional Review Inquiry Letter":

1) Proof materials that can be provided without conducting research;

2) There is no need to supplement new technical information, only need to explain the original declaration materials;

3) The review found that the deficiencies may need to be supplemented
.

Article 7 The applicant shall give an explanation or a written reply
within 5 working days of the issuance of the "professional review inquiry letter".
For those who require a written response, the applicant should file electronically within 5 working days; For registration applications accepted before the full implementation of electronic declaration, the applicant should also send the paper version consistent with the electronic version within the time limit, and download and print the "Professional Review Inquiry Letter" through the website of the Drug Review Center as the basis
for receiving supplementary information and inclusion in the file.

Chapter III Procedures for formal issuance, supplementary consultation, and objection

Article 8 If it is necessary for the applicant to supplement new technical information on the basis of the original declaration materials during the review process, combined with the response to the "professional review inquiry letter", according to the "Measures for the Administration of Drug Registration", the drug review center shall in principle submit a request for supplementary information, after listing all the questions.
Notify the applicant in writing to submit additional information
within 80 working days.

Article 9: The applicant shall submit all supplementary materials as required at one time within 80 working days, and the time for supplementary information shall not be included in the time limit
for drug review.

Article 10 After receiving all the supplementary information of the applicant, the drug review center will initiate the review, and the review time limit shall be extended by one-third; Where priority review and approval procedures apply, the time limit for review shall be extended by one-quarter
.

Article 11: If the applicant has any questions about the supplementary information requirements, he or she may submit an application for consultation on general technical issues through the website of the Drug Review Center within 10 working days of receiving the written supplementary information notice according to "issues related to the issuance of supplementary materials", and the project management personnel shall coordinate the indication team The reply shall be completed in writing or by meeting within 15 working days, and if a meeting is required, in principle, it shall be conducted
in the form of a telephone conference.

Article 12: Where the applicant still has objections to the reply to the supplementary consultation, he or she may submit the objection opinion through the website of the Drug Review Center within 10 working days of receiving the reply opinion, and the objection opinion shall specify the reasons and basis
.

Article 13: After receiving the applicant's objections, the Center for Drug Review shall organize relevant professional and technical committee meetings to conduct a comprehensive assessment
within 15 working days.

Article 14 After comprehensive assessment, if the drug review center finds that it is necessary to adjust the requirements for supplementary issuance, it shall conduct a new technical review within 3 working days, and inform the applicant
of the adjustment result through the drug review center's website.

Article 15: After a comprehensive assessment, the drug review center finds that there is no need to adjust the requirements for supplementary issuance, and within 3 working days, it shall inform the applicant through the website of the drug review center of the reasons and basis
for not agreeing to the objection to the issuance of supplements.

Chapter IV Supplementary Information Inquiry

Article 16: After the drug review center receives all the supplementary materials, the evaluation department will not issue supplements
in principle if it has doubts about the meaning of the supplementary materials or believes that there are problems with the content.
The chief examiner of each specialty drafts a "supplementary information inquiry letter", explaining the reasons and basis for failing to meet the requirements for issuing supplementary notices or not fully responding to the content of supplementary notices, and if new technical information is still required, it is recommended that the applicant take the initiative to withdraw the application matters and explain the reasons
.
After review by the person in charge of the review department, the applicant will be informed through the "supplementary information inquiry letter" on the website of the drug review center, and the review time limit will not be suspended
.

Article 17: Within 5 working days of the issuance of the "Supplementary Information Inquiry Letter", the applicant shall explain the supplementary materials or voluntarily withdraw the application matters
.
If the applicant does not reply to the "Supplementary Information Inquiry Letter" or does not agree to withdraw the review, the Drug Review Center will make a conclusion on the review of non-approval based on the existing application materials and publicize
it.
Applicants may raise objections in accordance with the Procedure for Resolving Objections
to Drug Registration Review Conclusions (Trial).

Article 18 For new safety indicators not stipulated in innovative drugs and guiding principles, the drug review center may reissue supplements according to the needs of review and communication with the applicant
.

Chapter V: Reminders of the expiration of the time limit for issuance and termination of review

Article 19: The website of the Drug Review Center will add a reminder function for the expiration of the time limit for supplementary information, and a reminder of the expiration of the time limit will be issued on the 5th working day before the expiration of the time limit required for supplementary information notification, reminding applicants to supplement information
on time.

Article 20 If the applicant fails to submit supplementary materials within the prescribed time limit, the Drug Review Center will handle the termination of the review procedure
in accordance with Article 92 (4) of the Measures for the Administration of Drug Registration.

Chapter VI Supplementary Provisions

Article 21: The Drug Review Center shall review the completeness of supplementary materials in accordance with the requirements for issuing supplements and the standards for receiving materials, and will not accept
materials that exceed the requirements for issuing supplements and the requirements of inquiry letters.

Article 22: If the applicant needs to resubmit the registration application after the termination of the review, he shall communicate with the drug review center in advance, and explain the perfection of the information and the conclusion of
the previous review in the application materials.

Article 23: This procedure shall take effect
on December 1, 2020.

Attach:

1.
Written supplementary standards for drug evaluation (trial).

2.
Professional review inquiry letter, supplementary information notice, supplementary information inquiry letter template

Attached 1 Written Supplementary Standards for Drug Evaluation (Trial).

In order to unify the standardization and necessity of the requirements for issuance of supplements and strictly control the number of supplements issued in the review process, according to the relevant provisions of the Measures for the Administration of Drug Registration and the actual work of drug technical review, the Drug Review Center has formulated the following standards for the issuance of supplements after research and discussion:

1.
According to the relevant requirements of the declaration materials, the declaration materials are inconsistent or inconsistent, unclear or non-standardized;

2.
According to laws, regulations and technical requirements, there are defects or imperfections in research design, test process and data analysis;

3.
There are differences or doubts between the research design and data analysis and the current scientific understanding and consensus;

4.
The writing of key contents such as quality standards, specifications, manufacturing and verification procedures, and production process information sheets is deemed to require major revisions after evaluation;

5.
Supplementary analysis of important safety and efficacy results;

6.
During the review process, relevant laws, regulations and technical guidelines are updated, and the review finds that it is necessary to supplement information related to the safety, efficacy or quality controllability of the drug;

7.
Major issues in the risk control plan;

8.
The basis for establishing the topic of the variety is not sufficient, and further information needs to be provided, such as unclear clinical positioning;

9.
APIs, excipients and packaging materials are not implemented in accordance with the current requirements of related review and approval and need to be supplemented, such as failure to register in accordance with the requirements of the announcement or failure to submit the information of the original and auxiliary packages in the application for pharmaceutical preparations, failure to provide authorization to associate with the pharmaceutical preparations, and the route of administration of the original and auxiliary packages does not meet the route of administration of the preparations, etc.
;

10.
It is necessary to conduct sample inspection, on-site inspection, and device-related review but not carried out, or problems found in production inspection, on-site inspection, and device-related review require supplementary information;

11.
Major safety accidents occur during the review process or major safety risks are found during the review process;

12.
Need to supplement information due to reporting;

13.
The original and auxiliary packages associated with the product are changed during the review process, or the problems found in the original auxiliary packages need to be solved through supplementary issues in the preparation review;

14.
More stability data needs to be collected during the review process to support the expiration date of the
product.

15.
After communicating with the applicant, if the evaluation finds that it is indeed necessary to issue supplements, and there are no provisions in the published supplementary standards, after study by the departmental technical committee, it shall be submitted to the director in charge of the center for review and approval, and the standards for updating the supplementary issued by the center can be implemented
only after they are released to the public.

Attached is 2 professional review inquiry letter, supplementary information notice, supplementary information inquiry letter template

1.
Professional review inquiry letter template

2.
Supplementary Information Notification Template

3.
Supplementary Information Inquiry Letter Template 

Declarations (templates)