Simplified Registration and Approval of Compound Preparations from Classic Traditional Chinese Medicine Formulas
Management Regulations (Draft for Comments) and Related Submission Requirements
(Draft for Comments) Explanatory Note
To implement thePeople's Republic of China"Traditional Chinese Medicine Law" (hereinafter referred to as the "TCM Law")Opinions of the State Council on Reforming the Review and Approval System for Drugs and Medical Devices (Guo Fa [2015〕44No., hereinafter referred to as44Document No.)The Drug Administration of the State Food and Drug Administration (SFDA) has drafted two supporting documents: "Provisional Regulations on Simplified Approval for Registration of Compound Preparations from Classic Chinese Medicine Formulas" (hereinafter referred to as the "Draft Regulations") and "Requirements for Submission Materials of Standard Decoctions for Compound Preparations from Classic Chinese Medicine Formulas" (hereinafter referred to as the "Requirements for Standard Decoction Submission Materials"), both in draft form for public comment. The following outlines the drafting process:
I. Background of the Drafted Regulations
2008The "Supplementary Provisions on the Registration Management of Traditional Chinese Medicine" implemented in {0} for the first time clarifiedTCM compound preparations derived from ancient classic formulas (hereinafter referred to as "classic formula preparations")registration management requirements.2015year44The notice further clarifies“Streamline approval of compound preparations derived from ancient classic formulas”。Traditional Chinese Medicine LawArticle 30 stipulates:“For traditional Chinese medicine compound preparations derived from ancient classic formulas that meet national regulatory requirements, only non-clinical safety study data may be submitted when applying for a drug approval number. Specific management measures shall be formulated by the drug regulatory authority under the State Council in conjunction with the traditional Chinese medicine competent department.”Accordingly, the CFDA is responsible for drafting registration documents related to classic patent formula preparations.
As shown,The "Traditional Chinese Medicine Law" incorporates"Supplementary Provisions on the Administration of Registration of Traditional Chinese Medicine" regardingClassic Prescription Preparationsmanagement regulations.
II. Drafting Process
From2015Year44After the issuance of the document, the Drug Registration Division of the CFDA strengthened its coordination withCoordinated with relevant bureaus of the State Administration of Traditional Chinese Medicine to jointly accelerate the drafting of documents related to preparations from classic formulas.
2017Year5Month12The Drug and Cosmetic Registration Division of the CFDA has established a team comprisingRelevant bureaus of the State Administration of Traditional Chinese Medicine, the National Pharmacopoeia Commission, and the Center for Drug Evaluation of the China Food and Drug Administration.A drafting working group composed of experts and enterprise representatives was established to define the approach and division of labor for compiling submission requirements related to classic prescription preparations.
2017Year6Month14Today, the Drug Evaluation Center of the State Food and Drug Administration convened a drafting working group meeting to specifically study the requirements for simplified approval of traditional Chinese medicine preparations based on classic formulas. Following the meeting, the Drug Evaluation Center organized the drafting of..."Provisions" and Related Submission Requirements (Discussion Draft).
2017Year7Month18Day,The Drug Registration Division of the China Food and Drug Administration has invited relevant departments of the State Administration of Traditional Chinese Medicine, the Legal Affairs Division of the China Food and Drug Administration, the National Pharmacopoeia Commission, and the Center for Drug Evaluation of the China Food and Drug Administration.Jiangsu, TianjinWait4one provincial food and drug regulatory department,TCM Association, Enterprise Representativesand related fields6Notable experts attended and further discussed the "Regulations" and related application requirements (draft). Key points focused on“Standard Decoction”The discussion focused on the submission of preparations based on classic famous prescriptions. Following the meeting, the Drug Registration Division of the CFDA reviewed the collected feedback, revised and finalized the draft, and issued it as a consultation document.
2017Year8At the beginning of the month, the Drug Registration Division of the China Food and Drug Administration (CFDA) solicited feedback from the National Administration of Traditional Chinese Medicine (NATCM), the CFDA Legal Affairs Division, the Drug Production and Operation Supervision Division, and the Center for Drug Evaluation. Based on the received comments, the draft was revised and finalized.
III. Key Content and Instructions
The "Regulations (Draft for Comments)" includes a total of21items, with content sequentially covering the scope of classic famous prescriptions,Simplified approval conditions and applicant qualifications“Standard Decoction”Declaration and publication, registration procedures and management requirements for classical formula preparations, responsibilities of relevant parties, etc. The "Requirements for Declaration Materials of Standard Decoctions (Draft for Comments)" mainly discusses“Standard Decoction”Technical requirements for research, focusing on medicinal materials-Decoction pieces-“Standard Decoction”serves as the main thread; "Requirements for Declaration Materials of Classic Prescriptions (Draft for Comments)" is mainly divided into: general summary materials, pharmaceutical research materials, andNon-clinical safety study data, Part 3: Pharmaceutical research data adoptedHerbal medicine-Decoction pieces-“Standard Decoction”-Presentation of the formulation. Key points are as follows:
(I) AboutStandard Decoction
Classic formulas in China have a long and rich history of human use. However, due to unstable raw herbs and complex compositions, batch-to-batch consistency is critical for ensuring consistent therapeutic efficacy. To address this, the Drug Registration Division of the State Food and Drug Administration introduced“Standard Decoction”management requirements, using it as a reference material for quality control. However, should the wording be retained?“Standard Decoction”naming conventions, experts raised different opinions. Some experts believe that traditional Chinese medicine originated in China and should not adopt Japanese terminology. Others have suggested using...“Standard Formulation”“Original Formula Preparation”the expression, but due to“Formulation”The term "ready-made product concept" is easily misunderstood, so it was not adopted.
After review, the Drug Registration Division of the China Food and Drug Administration now adopts“Standard Decoction”The rationale is primarily based on the following two points: first,“Standard Decoction”in“Standard”refers to the quality of the formulation“baseline”is used as a standard reference to determine consistency with medicinal substances employed in traditional Chinese medicine clinical practice; secondly,“Standard Decoction”in“Decoction”Vividly recreates the clinical medication methods of classic famous formulas, thereby emphasizing consistency with traditional Chinese medicine (TCM) clinical practices. Although some classic famous formulas are administered as powders rather than decoctions, the Drug and Chemical Registration Division of the State Food and Drug Administration uses "standard decoction" in quotes to achieve a representative approach.
(II) Regarding the phased submission of documents
Due to“Standard Decoction”It serves as the quality benchmark for classic formula preparations; therefore, each classic formula should correspond to one.“Standard Decoction”(except for classic formulas containing multiple botanical sources in prescriptions), this requires the generation of“Standard Decoction”before developing corresponding classic formula preparations. Given that multiple applicants may submit for the same variety, a relatively unified approach is needed.“Standard Decoction”As a benchmark to ensure consistent quality of the same classic formula preparation across different manufacturers, when the China Food and Drug Administration releases a specific classic formula“Standard Decoction”Under the Standard, applications for production of classic patent medicine preparations may be submitted in stages:Applicants may initially provide only“Standard Decoction”Related application materials, in“Standard Decoction”Submit supplementary application materials for classic prescription preparations after the standard is published. The applicant may request an extension of the submission deadline based on research needs and must provide reasons to the CDE of the NMPA.
Submit First“Standard Decoction”Afterwards, the Drug Evaluation Center proceeds to6After the one-month public notice period, other entities may continue to submit applications. Upon completion of the notice period, the Center for Drug Evaluation (CDE) of the National Medical Products Administration will review all received applications for the same classic formula.“Standard Decoction”Undergo review and be published by the State Food and Drug Administration.“Standard Decoction”Standard.
(3) Quality Control
CNFinished Product Quality IToSex has always been a challenge in the quality control of traditional Chinese medicine (TCM). Relying solely on end-product standard testing has significant limitations. To ensure the quality and efficacy of classic formula preparations...ToQuality control measures must be established across the entire supply chain—from raw herbs to processed slices, intermediates, and finished preparations—and the entire process must align with“Standard Decoction”Compare. In quality comparison and control,The metrics and methods for quality assessment are critical. The selection of metrics mustConsider herbs comprehensively-Decoction pieces-“Standard Decoction”-Formulationrelevance to clinical efficacy. The quality of intermediates and finished products should be controlled using holistic approaches such as fingerprint or characteristic profile methods, with encouragement for the use of bioactivity assays. Additionally, the Drug Registration Division of the China Food and Drug Administration has incorporated advanced international concepts in quality control.“Quality Attributes”Per the requirements, applicants must study physicochemical and biological quality attributes that impact drug safety, efficacy, or consistency, and select appropriate evaluation indicators based on these findings.
（4. Nonclinical Safety Studies
Although classic formulas have a long history of human use, they have lacked systematic preclinical safety studies; Ministry of Science and Technology“12th Five-Year Plan”Regarding the specialIn nonclinical safety studiesIndividual classical formulas have been found to pose significant safety risks, underscoring the need for further evaluation of classical formula preparations.Nonclinical Safety StudiesAdditionally, some medicinal materials have multiple botanical sources, and using different sources may lead to varying safety risks. Therefore, to ensure public medication safety, regulations require that applicants for each classic prescription formulation systematically and thoroughly conductNonclinical Safety Studies。
(V) Coordination with Other Drug Registration Systems
The draft "Provisions" has added a catch-all clause to ensure smooth alignment of the registration and marketing authorization holder system for classic name formulas with other relevant registration management systems.