Notice on Issuing the Supplementary Provisions for the Administration of Traditional Chinese Medicine Registration
CFDA Approval No. 20083
Published on 01/07/2008
Food and Drug Administration (Drug Supervision Bureau) of each province, autonomous region, and municipality directly under the Central Government; General Logistics Department Health Department Drug Supervision Bureau:
To align with the principles of traditional Chinese medicine (TCM) research, reflect the unique characteristics of TCM registration, standardize TCM registration practices, and promote the development of TCM and ethnic medicine, the National Medical Products Administration has formulated the "Supplementary Provisions on TCM Registration Management" in accordance with relevant provisions of the "Drug Registration Management Measures." These provisions are hereby issued for implementation.
National Medical Products Administration
January 7, 2008
Supplementary Provisions on the Registration Administration of Traditional Chinese Medicine
Article 1: To highlight the distinctive features of traditional Chinese medicine (TCM), adhere to the principles of TCM research, inherit traditional knowledge, encourage innovation, and support the development of TCM and ethnic medicine, these supplementary provisions are formulated in accordance with the "Measures for Drug Registration."
Article 2: The development of new Chinese medicines shall align with traditional Chinese medicine theory, be grounded in clinical practice, and demonstrate clinical value. It must ensure the safety, efficacy, and consistent quality of these medicines, guarantee stable sourcing of medicinal materials, promote sustainable resource utilization, and consider environmental impacts. Where endangered wild flora or fauna are involved, compliance with national regulations is required.
Article 3: New drugs whose indications are not listed in the approved "Indications and Functions" of Chinese patent medicines by the state fall within the scope of Item (4) of Paragraph 1, Article 45 of the "Measures for the Administration of Drug Registration."
Article 4: For traditional Chinese medicine (TCM) registration applications, the following shall be clearly specified: the prescription composition, plant source of medicinal materials, origin and resource status of materials, and pre-processing procedures (including processing), extraction, separation, purification, and formulation processes. Key process parameters must also be defined.
Article 5: Compound traditional Chinese medicine preparations shall be formulated under the guidance of TCM theory. Their formulations may include processed Chinese medicinal materials (herbs), extracts, active fractions, and active ingredients.
If the Chinese herbal medicine contains ingredients without established standards, a separate quality standard must be established. For active parts or components without established standards, a separate quality standard should be developed, and research data corresponding to the applicable registration category must be submitted. Quality standards for Chinese herbal extracts must be established with controllable parameters and attached following the dosage form's quality standard.
Article 6: In addition to providing overview and pharmaceutical research data, Chinese patent medicines shall submit relevant pharmacological/toxicological and clinical trial data in accordance with the requirements set forth in Articles 7, 8, and 9 for each category.
Article 7: Traditional Chinese medicine compound preparations derived from ancient classic formulas refer to prescriptions recorded in medical texts from the Qing Dynasty or earlier that are still widely used today, have proven efficacy, and possess distinct characteristics and advantages.
(1) The specific catalog of such Chinese patent medicines shall be formulated and published by the China Food and Drug Administration in coordination with relevant departments.
(2) Chinese proprietary compound preparations meeting the following criteria may submit only non-clinical safety data and apply directly for production:
1. The prescription contains no toxic herbs or incompatible combinations.
2. All prescribed Chinese herbal ingredients must comply with statutory standards;
3. The production process is essentially the same as traditional methods;
4. The route of administration is consistent with ancient medical records, and the daily dosage of decoction pieces is comparable to that recorded in ancient texts.
5. Indications and functions are consistent with ancient medical records;
6. Indications do not include critical or severe conditions, and the product is not intended for use in pregnant women, infants, or young children.
(3) The drug label for this type of TCM compound preparation must specify the exact source of the prescription and its indicated functions and therapeutic effects, demonstrate a long history of clinical use, and provide non-clinical safety evaluation data.
(4) New drug certificates shall not be issued for this type of TCM compound preparation.
Article 8: A Chinese herbal compound preparation indicated for TCM syndromes refers to a compound preparation of Chinese herbs used to treat TCM syndromes under the guidance of TCM theory, including those used to treat diseases or symptoms in traditional Chinese medicine.
(1) The prescription composition of such traditional Chinese medicine (TCM) compound preparations shall comply with TCM theory, have a basis for clinical application, and its functions and indications must be expressed using TCM terminology.
(2) The State Food and Drug Administration's Center for Drug Evaluation shall organize traditional Chinese medicine experts to review the prescription sources, formulation rationale, clinical application status, indications, dosage, and administration of this type of TCM compound preparation.
(3) Efficacy assessment shall be primarily based on Traditional Chinese Medicine (TCM) syndromes. Clinical trials validating syndrome-specific efficacy may employ various study designs, provided that the scientific rationale is clearly explained. The sample size must meet biostatistical requirements, and trial results must demonstrate statistical significance.
(4) For products with sufficient clinical application data and where the manufacturing process, dosage, and administration are consistent with prior clinical use, only non-clinical safety data may be submitted; clinical studies may proceed directly to Phase III trials.
(5) If the manufacturing process, usage, or dosage differs from prior clinical applications, nonclinical safety study data and pharmacodynamic study data must be provided. Pharmacodynamic studies should use animal models of Traditional Chinese Medicine (TCM) syndromes; if mature TCM syndrome animal models are unavailable, it is encouraged to conduct primary pharmacodynamic trials relevant to the drug's indicated functions and therapeutic effects. Clinical development shall include Phase II and Phase III clinical trials.
(6) For this category of TCM compound preparations, the "Clinical Trials" section of the drug labeling must primarily describe efficacy on TCM syndromes and may also address effects on related diseases.
Article 9: In Chinese herbal compound preparations that treat both disease and syndrome, "disease" refers to a condition defined by modern medicine, while "syndrome" refers to a TCM pattern. The functions are expressed using professional TCM terminology, and the indications are described as a combination of modern medical diseases and TCM syndromes.
(I) The prescription composition of this category of traditional Chinese medicine compound preparations shall comply with TCM theory and have a certain foundation in clinical application.
(2) Where there is sufficient clinical application data and the production process, dosage, and administration are substantially consistent with prior clinical use, only non-clinical safety study data may be submitted; clinical studies must include Phase II and Phase III trials.
(3) If the manufacturing process, usage, or dosage differs from prior clinical applications, nonclinical safety study data must be provided, and major pharmacodynamic studies should be conducted based on the proposed indications. Pharmacodynamic research should generally employ animal models of Traditional Chinese Medicine (TCM) syndromes or disease models. Where mature TCM syndrome or disease models are unavailable, major pharmacodynamic studies related to the function (pharmacological effects) may be performed. Clinical trials must include Phase II and Phase III studies.
Article 10: For registration applications involving a change in dosage form of an already marketed drug without altering the route of administration, sufficient evidence must be provided to demonstrate scientific rationale. New technologies should be employed to enhance the drug's quality and safety, and the new formulation must offer clear clinical advantages over the original dosage form.
(1) If there are changes to the botanical origin of the medicinal material, the production process (including pretreatment, extraction, separation, purification, etc.), process parameters, or the formulation, but the chemical basis remains largely unchanged and the dosage form change has minimal impact on drug absorption and utilization, pharmacological and toxicological study data may be provided as needed. Clinical trials must include at least 100 pairs of cases. For indications involving multiple conditions, each primary condition must have at least 60 pairs of cases.
(2) If there are significant changes in the botanical source of medicinal materials, production processes (including pre-treatment, extraction, separation, purification, etc.), process parameters, or formulation composition that substantially alter the pharmacological basis, or if a change in dosage form significantly affects drug absorption and utilization, relevant pharmacological/toxicological studies and Phase II and III clinical trial data must be provided.
(3) The rationale for sustained-release and controlled-release formulations should be based on the pharmacokinetic parameters of the immediate-release formulation in humans and clinical needs. Preclinical studies must include comparative data on pharmaceutical and biological properties between the modified-release and immediate-release formulations. Clinical studies should provide human pharmacokinetic data as well as comparative data on efficacy and safety to demonstrate the unique release characteristics and advantages of these formulations.
Article 11. Applications for registration of generic drugs must maintain consistency with the reference listed drug in terms of formulation composition, plant material origin, manufacturing process (including pre-processing, extraction, separation, purification, etc.), and process parameters, as well as excipient formulation. The quality controllability of the generic drug shall not be lower than that of the reference listed drug. If specific process parameters or excipient formulations cannot be confirmed to be consistent with those of the reference listed drug, comparative studies shall be conducted to ensure quality consistency, followed by clinical trials involving at least 100 pairs of subjects or human bioequivalence studies.
Article 12: For supplementary applications involving changes to excipients with established medicinal requirements in an existing drug prescription, if the prescription contains no toxic ingredients and the change in excipients is not expected to significantly affect drug absorption or utilization, nor cause significant changes in safety or efficacy, pharmacological/toxicological study data and clinical trial data may be omitted. However, if the change in excipients may significantly affect drug absorption or utilization, relevant pharmacological/toxicological study data and Phase II and Phase III clinical trial data must be provided.
Article 13: For supplementary applications to modify production processes that affect drug quality, pharmacological and toxicological study data and clinical trial data may be omitted if the prescription contains no toxic herbs, the process change does not alter the material basis of the drug, has no significant impact on absorption or bioavailability, and does not significantly affect safety or efficacy. If the process change affects the material basis but only minimally, with no significant impact on absorption or bioavailability, pharmacological and toxicological study data may be omitted; however, a clinical trial with at least 100 matched pairs is required. For indications involving multiple conditions, each major condition must include at least 60 matched pairs. If the process change causes a significant alteration in the material basis or may significantly affect drug absorption or bioavailability, relevant pharmacological and toxicological study data and Phase II and Phase III clinical trial data must be submitted.
Article 14: For registration applications involving changes to the dosage form, manufacturing process, or route of administration of an approved drug that require pharmacological studies, efficacy trials shall be conducted with the original dosage form, original manufacturing process, or original route of administration as the control (the control may consist of a single high-dose group only).
Article 15: For registration applications of new effective fraction preparations, if a single-herb preparation with substantially the same indications is already on the market, comparative nonclinical and clinical studies must be conducted against that single-herb preparation to demonstrate the advantages and characteristics of the new preparation.
Article 16. Samples used in non-clinical safety studies shall be from pilot scale or larger. Samples for clinical trials shall generally be from production scale; however, for preparations made from active ingredients or active components, samples from pilot scale or larger may be used.
Article 17: For TCM registration applications involving toxic herbs in prescriptions, raw materials without statutory standards, or non-clinical safety studies showing significant toxic reactions or other clinical safety concerns, Phase I clinical trials shall be conducted.
Article 18: For new drug registration applications, applicants may request phased (Phase I, II, III) clinical trials based on specific circumstances and may submit non-clinical safety data supporting each corresponding trial phase.
After completing a phased clinical trial, you may apply for the next phase via a supplementary application.
Article 19: Clinical trials must select control drugs based on principles such as trial objectives, scientific rationale, and feasibility. The use of placebos must comply with ethical requirements, and the selection of active comparators must be supported by sufficient clinical evidence. For traditional Chinese medicine preparations that modify the dosage form or manufacturing process of an already marketed drug, or that adjust the formula while maintaining substantially consistent indications and functions, the corresponding marketed drug shall be selected as the active comparator.
Article 20: During clinical trials, the manufacturing process and specifications of the preparation may be adjusted based on study findings. If such adjustments could potentially affect efficacy or safety, a supplementary application must be submitted along with relevant supporting data.
Article 21: Registration and management of ethnic medicines, including Tibetan medicine, Uyghur medicine, and Mongolian medicine, shall be governed by these Regulations. The development of ethnic medicines must align with the theories of ethnic traditional medicine. Enterprises applying for production shall possess qualified ethnic medicine professionals, as well as the necessary production conditions and capabilities. Evaluation shall be conducted by experts specializing in ethnic medicines.
Article 22 These provisions shall take effect on the date of promulgation.