On April 30, the official website of the State Food and Drug Administration also posted 18 drafts for public comments, and the deadline for feedback is May 30, 2020.

5 supporting documents related to chemical drug registration and change

"Chemical Drug Registration Classification and Application Materials Requirements (Draft for Comment)"

"Changes of Listed Chemical Drugs and Requirements for Application Materials (Draft for Comment)"

"Technical Guiding Principles for Pharmaceutical Change Research of Listed Chemicals (Draft for Comment)"

"Guidelines for the Acceptance and Review of Chemical Drug Registration (Draft for Comment)"

"Guidelines for Acceptance and Review of Chemical Drug Changes (Draft for Comment)"

6 supporting documents related to registration and modification of traditional Chinese medicine

"Special Regulations on Registration and Administration of Traditional Chinese Medicine (Draft for Comment)"

"Chinese Medicine Registration Classification and Application Materials Requirements (Draft for Comment)"

"Changes of Listed Chinese Medicines and Requirements for Application Materials (Draft for Comment)"

"Technical Guiding Principles for Pharmacy Change Research of Listed Chinese Medicines (Draft for Comment)"

7 supporting documents related to the registration and modification of biological products

"Biological Product Registration Classification and Application Materials Requirements (Draft for Comment)"

"Classification of Changes in Listed Biological Products and Requirements for Application Materials (Draft for Comment)"

"Technical Guiding Principles for Pharmaceutical Change Research of Listed Biological Products (Draft for Comment)"

"Guidelines for the Acceptance and Review of Registration of Biological Products (Part 1: Biological Products for Prophylaxis) (Draft for Comment)"

"Guidelines for the Acceptance and Review of Registration of Biological Products (Part II: Therapeutic Biological Products) (Draft for Comment)"

"Guidelines for the Acceptance and Review of Registration of Biological Products (Part III In Vitro Diagnostic Reagents Managed by Biological Products) (Draft for Comment)"

"Guidelines for the Review of Changes in Biological Products (Draft for Comment)"

Chemical drugs: add the classification of "chemical drugs that have been listed overseas and not listed in China"

Comparing the consultation draft of chemical drug registration and related supporting documents with the 2020 new version of the "Administrative Measures for Drug Registration", it can be found that the classification of chemical drug registration has been updated: in addition to the existing three categories of innovative drugs, improved new drugs and generic drugs In addition, the classification of "chemical drugs that have been listed overseas and not listed in China" has also been added.

The increase of this part can be said to be in response to the supplementary opinions put forward by industry insiders on the actual situation of the domestic pharmaceutical industry when the upper law was announced.

According to the drafting instructions, the registration classification is to classify new drugs into innovative drugs and improved new drugs according to the novelty and originality of the material basis, all of which are unmarketed drugs at home and abroad and have clinical value. Generic drugs produced in China are divided into 3 categories and 4 categories according to whether their imitated original research products have been marketed in China. The drugs that have been marketed overseas are divided into 5 categories, 5.1 category is original research drugs and improved drugs, 5.2 category is generic drugs.

According to the "Guidelines for the Acceptance and Review of Chemical Drug Registration (Part 1 + Registration Classification 1, 2, 5.1) (Draft for Comment)" released at the same time, Category 5.1 will be managed as a new drug. Therefore, for the restriction on the registration of the same variety during the monitoring period, it will continue to follow the principle of "starting from the date when the new drug enters the monitoring period, other applicants' applications for the same variety registration will not be accepted; if the clinical application has been approved, the application for marketing authorization can be accepted".

From the "Acceptance Guidelines" (Draft for Comment), the new requirements, new concepts and new formulations in the "Drug Administration Law" and "Drug Registration Management Measures" have been incorporated, such as accelerated marketing registration procedures, bioequivalence Contents that have received high attention in the industry, such as sex filing, inspection of series-to-parallel conversion, etc., are all involved.

In addition, in order to further promote the integration with international standards and lay a solid foundation for electronic submission of drug registration (eCTD), the official Chinese version of "M4: General Technical Document (CTD) for Human Drug Registration Application" was released in April last year. Therefore, this The second draft also clarified that all drug marketing, clinical trials and API applications should be submitted in the CTD format.

Traditional Chinese Medicine: Clarify the conditions for exempting clinical trials of drugs with the same name and the same formula, and integrate human experience into the review evidence system

Compound preparations with classical names and drugs with the same name are the two major categories clearly defined in the 2020 new version of the "Administrative Measures for Drug Registration". The "Special Regulations on Registration and Administration of Traditional Chinese Medicines (Draft for Comment)" not only clarifies the definition of the same name and the same prescription - referring to the generic name, prescription, dosage form, functions and indications, usage and daily dose of decoction pieces that are the same as those of the listed traditional Chinese medicine, The safety, efficacy and quality controllability shall not be inferior to the preparation of the marketed traditional Chinese medicine. In addition, the consultation draft also emphasizes that there should be sufficient evidence for the selection of the same-name and same-prescription drugs. Registration applicants are required to provide sufficient evidence-based evidence on the safety and effectiveness of the same-name and same-name drugs when applying for drug marketing, and clinical trial materials should be provided when necessary.

At the same time, it is also clarified that clinical trials comparing with reference drugs need to adopt non-inferiority design for phase III clinical and clinical trial design. The active ingredient of traditional Chinese medicine can be proved to be consistent with the control drug of the same name and the same formula through the bioequivalence test. If the medicinal material base, decoction piece processing, ointment production rate, content and content transfer rate of effective (or index) ingredients, fingerprint or characteristic map, etc. are consistent with the same-named and controlled same-name medicines applied for registration, the clinical application can be exempted. test.

In addition, considering that many new traditional Chinese medicines have some human experience before they go on the market, or the prescriptions are derived from classic prescriptions, test prescriptions, or have been prepared into medical institutions. Some scientific research parties will also obtain preliminary human experience of traditional Chinese medicine through the development of clinical research. This "Special Regulations on the Administration of Traditional Chinese Medicine Registration (Draft for Comment)" also clarifies the requirements for evidence of human use experience and the reasonable reduction and exemption of application materials, and integrates the existing human experience of traditional Chinese medicines into the evaluation evidence system of traditional Chinese medicines. Characteristics of the review and approval technology evaluation system entry point. It not only clarifies the requirements for human experience of traditional Chinese medicine as evidence to support the safety and effectiveness of traditional Chinese medicine; it also clarifies the circumstances under which the corresponding application materials can be reduced or exempted; it also proposes to introduce real-world research as human experience of traditional Chinese medicine.

Biological products: registration classification is defined according to the maturity level at the time of declaration

The registration of biological products has been clearly classified in the 2020 new version of the "Administrative Measures for Drug Registration" according to biological product innovative drugs, biological product improved new drugs, and marketed biological products (including biosimilars). In the "Registration Classification and Application Materials Requirements for Biological Products (Draft for Comment)" released this time, biological products for prevention (vaccine), biological products for treatment and in vitro diagnostic reagents managed by biological products are separately expressed. Biological products are registered in accordance with the new drug procedures; in vitro diagnostic reagents and intramuscular injection of general or specific human immunoglobulin, human albumin, etc. are exempted from clinical trials according to regulations, and they can directly submit a marketing application. The registration classification should be defined according to the maturity level of the product at the time of application for registration, and will not be changed during the review process.

Judging from the registration classification of vaccines and the requirements for application materials, a lot of strict details have been added. For example, the new adjuvant vaccines classified as improved vaccines in the 2017 version of the "Administrative Measures for Drug Registration (Revised Draft)" will be managed in Category 1 innovative vaccines this time. For overseas applicants who apply for clinical trials of vaccines for minors in China, it is proposed to obtain at least Phase I clinical trial data that includes target populations abroad (vaccines urgently needed in response to major public health emergencies or the State Council health director Except for other vaccines deemed urgently needed by the department).

Therapeutic biological products are also divided into three categories according to the degree of product maturity, and the application materials are written in accordance with the "M4: General Technical Document (CTD) for Registration of Human Drugs" (hereinafter referred to as CTD). However, the document also reminds that due to the continuous development of biological products Innovation and the stage of application, the specific content of the application materials should not only meet the requirements of the CTD format, but also meet the requirements of the relevant regulations and technical guidelines that are constantly updated. Sufficient basis for providing support.

For in vitro diagnostic reagents managed according to biological products (including in vitro diagnostic reagents for blood source screening, in vitro diagnostic reagents labeled with radionuclides, etc.) Two categories. If it is an overseas applicant, it is required to provide the clinical trial data completed overseas, the summary report of overseas clinical use and the clinical trial data completed in China.