Notice from the National Medical Products Administration on the Release of Classification of Chemical Drug Registration and Requirements for Submission of Application Materials

　　(No. 44 of 2020)

　　Release date: 2020-06-30

　　To align with the implementation of the “Measures for the Administration of Drug Registration,” the National Medical Products Administration has organized the development of the “Classification of Chemical Drug Registration and Requirements for Submission of Application Materials.” This document is now released, and the following explanations are provided:

　　I. Regarding the classification of chemical drug registration, the new regulations have been implemented since July 1, 2020.

　　II. Regarding the requirements for registration application materials for chemical drugs, these shall take effect as of October 1, 2020. Prior to September 30, 2020, applicants may still submit application materials in accordance with the original requirements.

　　Hereby notified.

　　Attachment: Classification of Chemical Drug Registration and Requirements for Submission of Application Materials

　　National Medical Products Administration

　　June 29, 2020

　　Attachment

　　Classification of Chemical Drug Registration and Requirements for Submission of Application Materials

　　I. Classification of Chemical Drug Registration

　　The registration categories for chemical drugs are divided into innovative drugs, improved new drugs, generic drugs, and chemically manufactured drugs that have been approved for marketing overseas but not yet in China. These categories are further subdivided into the following five classes:

　　Category 1: Innovative drugs that have not been marketed either domestically or internationally. These are pharmaceutical products containing new, structurally defined compounds with established pharmacological activity and clinical value.

　　Category 2: Improved new drugs that have not been marketed either domestically or internationally. These are pharmaceutical products that, based on known active ingredients, have undergone optimization in terms of their structure, dosage form, formulation process, route of administration, indications, and other aspects, and demonstrate clear clinical advantages.

　　2.1 Pharmaceuticals containing optical isomers of known active ingredients prepared by methods such as resolution or synthesis, or esterified forms of known active ingredients, or salt forms of known active ingredients (including salts involving hydrogen bonds or coordination bonds), or those in which the anion, cation, or metallic element of a known salt-based active ingredient has been altered, or those forming other non-covalent bond derivatives (such as complexes, chelates, or inclusion compounds) and demonstrating significant clinical advantages.

　　2.2 New dosage forms (including new delivery systems) containing known active ingredients, new formulation processes, and new routes of administration, which demonstrate clear clinical advantages.

　　2.3 New combination formulations containing known active ingredients and demonstrating clear clinical advantages.

　　2.4 Drugs with new indications containing known active ingredients.

　　Category 3: Drugs that are generic versions of originator drugs already marketed overseas but not yet marketed in China, submitted by applicants within China. Such drugs should be consistent with the reference preparation in terms of quality and efficacy.

　　Category 4: Medicines that are generic versions of originator drugs already marketed in China, submitted by applicants within China. Such medicines shall be consistent with the reference preparation in terms of quality and efficacy.

　　Category 5: Applications for drugs listed overseas to be approved for listing in China.

　　5.1 Applications for the domestic marketing of originator drugs and improved-version drugs that are already listed overseas. Improved-version drugs must demonstrate clear clinical advantages.

　　5.2 Application for generic drugs listed overseas to be approved for listing in China.

　　An originator drug refers to the first drug approved for marketing, both domestically and internationally, that has complete and sufficient safety and efficacy data serving as the basis for its approval.

　　A reference listed drug refers to the control drug used in the development of generic drugs, as evaluated and confirmed by the national drug regulatory authority. The selection and publication of reference listed drugs shall be carried out in accordance with relevant regulations of the national drug regulatory authority.

　　II. Relevant Registration and Management Requirements

　　(1) Chemical drug Class 1 refers to innovative drugs that must contain new, structurally defined compounds with pharmacological activity and clinical value. This category does not include drugs classified as Class 2.1 under the category of improved new drugs. New combination preparations containing new, structurally defined compounds with pharmacological activity shall be submitted for approval according to the requirements for Chemical Drug Class 1.

　　(2) Category 2 chemical drugs are improved new drugs that have been optimized based on known active ingredients and should demonstrate clear clinical advantages over the original formulation. "Known active ingredients" refer to the active ingredients of drugs already marketed domestically or internationally. If a drug in this category meets requirements under multiple criteria simultaneously, such information must be disclosed at the time of application.

　　(3) Category 3 chemical drugs are generic versions of originator drugs that have already been marketed overseas but not yet approved for marketing in China. These drugs have the same active ingredients, dosage forms, specifications, indications, routes of administration, and dosages as the reference preparations, and their quality and efficacy have been demonstrated to be consistent with those of the reference preparations.

　　Where there is sufficient research data to support its rationale, the specifications and dosage regimen may differ from those of the reference product.

　　(4) Category 4 chemical drugs are generic versions of originator drugs already marketed in China, produced domestically. These drugs have the same active ingredients, dosage forms, specifications, indications, routes of administration, and dosages as the reference preparations, and their quality and efficacy have been demonstrated to be consistent with those of the reference preparations.

　　(5) Category 5 of chemical drugs refers to applications for the approval of drugs already marketed overseas to be launched in China, including both domestically and overseas-produced drugs. Among these, Category 5.1 covers original innovative drugs and improved new drugs. Improved new drugs, which are optimized based on known active ingredients, must demonstrate clear clinical advantages over their earlier versions. Category 5.2 covers generic drugs, which must prove that they are bioequivalent to the reference listed drug in terms of quality and efficacy; their technical requirements are identical to those for Category 3 and Category 4 chemical drugs. Generic drugs produced overseas that are simultaneously developed both domestically and abroad should be submitted under Category 5.2. If such a drug is being applied for clinical trials, there is no requirement to provide documentation proving that the drug has been approved for marketing and sale.

　　(6) For already-marketed drugs, adding new indications that have been approved overseas but not yet approved domestically shall be submitted via the clinical trial and marketing authorization application pathway.

　　(7) During the review and approval process for a drug’s marketing application, the drug registration classification and technical requirements shall not change simply because formulations containing the same active ingredient have been approved for marketing both domestically and internationally. The drug registration classification is determined at the time of submission of the marketing application.

　　III. Requirements for Application Materials

　　(1) Applicants submitting applications for clinical trials of drugs, marketing authorization of pharmaceutical products, and active pharmaceutical ingredients shall conduct their studies in accordance with the relevant requirements set forth in the technical guidance principles published by the national drug regulatory authority. They shall also organize and submit their application materials following the format and sequence of items specified in the current version of “M4: Common Technical Document (CTD) for Regulatory Filing of Human Medicinal Products” (hereinafter referred to as the CTD). For items that are not applicable, reasonable omissions are permitted; however, such items must be clearly marked as inapplicable, along with a statement of the reasons for their non-applicability.

　　(2) When an applicant submits a drug registration application after completing a clinical trial, it shall submit an electronic clinical trial database based on the CTD. Specific requirements regarding the database format and related documents can be found in the relevant guidelines for submitting clinical trial data.

　　(3) The Drug Review Center of the National Medical Products Administration will, based on the needs of drug review work and in conjunction with revisions to ICH technical guidelines, promptly update the CTD documents and publish them on the Center’s website.