At a symposium with experts and scholars held on June 2, General Secretary Xi Jinping emphasized: “We must strengthen the systematic collation and excavation of the essence of classical medical texts, establish a number of research-support platforms, reform and improve the review and approval mechanism for traditional Chinese medicines, and promote the research and development of new TCM drugs as well as the growth of the TCM industry.”

Recently, the State Administration of Traditional Chinese Medicine released the first batch of seven classic ancient prescriptions under the “Opinions on the Verification of Key Information for Time-Honored Classical Formulas,” and is now soliciting extensive public input.

In 2008, the former State Food and Drug Administration issued the “Supplementary Provisions on the Registration and Management of Traditional Chinese Medicines,” stipulating that “complex formulations of traditional Chinese medicines derived from time-honored classic prescriptions may submit only non-clinical safety study data and proceed directly to application for manufacturing approval.”

How many hurdles must be overcome to transform a “formula” into a “medicine”? A reporter conducted an investigative interview on this very question.

From over 100,000 prescriptions recorded in more than a hundred representative ancient medical texts, we have carefully selected the classic renowned formulas through a step-by-step screening process, truly achieving a ratio of one in a hundred.

Eighty-one-year-old Grandma Chen lives in Jianggan District, Hangzhou City, Zhejiang Province. Recently, she had lost her appetite and felt no desire to eat, so she sought out Professor Lian Jianwei of Zhejiang University of Traditional Chinese Medicine. After taking her pulse and examining her tongue coating, Professor Lian asked, “Do you have a tender area on your back about the size of a palm?” Grandma Chen replied, “Yes, there is indeed a spot on my back.” He then inquired whether she was experiencing dizziness or chest fullness, and she confirmed both. Grandma Chen joked that if it hadn’t been for the doctor’s question, she would never have remembered these symptoms herself. Professor Lian explained that her symptoms are typical and are documented in classical texts of traditional Chinese medicine. After three weeks of herbal treatment, all of Grandma Chen’s symptoms had completely resolved.

Lian Jianwei prescribed Ling Gui Zhu Gan Tang, a formula recorded in the “Jin Gui Yao Lue.” The prescription, preparation method, and dosage are as follows: four liang of Poria, three liang each of Cinnamon Twig and Atractylodes, and two liang of Licorice; decoct in six sheng of water until three sheng remain, then divide into three doses to be taken warm. Lian Jianwei emphasized that ancient formulas cannot be applied today simply by following the original prescriptions as recorded in classical texts. When the dosages in these texts are converted according to the traditional units of measurement, they often differ substantially from contemporary standard dosages. He therefore recommends conducting systematic research into the correspondence between ancient and modern systems of measurement, exploring methods for converting historical units of volume and weight, establishing clear procedures for translating ancient formula dosages into modern equivalents, and defining appropriate modern dosages—thus enabling classic ancient formulas to be integrated into modern clinical practice.

Chen Ronghu, Deputy Director of the Science and Technology Department of the State Administration of Traditional Chinese Medicine, stated that time-honored classic prescriptions have a long history of clinical application. Throughout various historical periods, their evolution has been accompanied by numerous challenges, including changes in the botanical origins of medicinal materials, conversions between traditional and modern systems of measurement, and the translation of ancient processing methods into contemporary manufacturing techniques. Moreover, the ambiguity surrounding key information—such as the botanical origins of herbs, processing techniques, dosage conversions, and decoction methods—has directly impeded drug development and become a major bottleneck in the registration and review of preparations derived from these ancient classic formulas.

The verification of key information regarding classic prescriptions should not be confined to a single historical period. Take Citri Fructus Immaturus as an example: was the raw material derived from bitter orange or sweet orange? According to Huang Luqi, prior to the Song Dynasty, the predominant botanical source was Poncirus trifoliata of the Rutaceae family. However, since the Song Dynasty, medical practitioners have held that bitter orange, with its characteristic “inverted-belly shape resembling the rim of a basin,” is of superior quality, while considering Poncirus trifoliata “unsuitable for use,” thus leading to a shift in the botanical source to bitter orange. The Chinese Pharmacopoeia stipulates that sweet orange may also serve as the source of Citri Fructus Immaturus; yet its quality is inferior to that of bitter orange, making bitter orange the preferred choice.

How to translate traditional medicinal practices into modern manufacturing processes while maintaining consistency in quality attributes is a practical challenge in the research and development of time-honored classic formulas. In the “Yangwei Decoction” from the Ming Dynasty’s “Zhengzhi Zhunsheng,” the herb Cangzhu is explicitly prescribed to be processed by “soaking and washing in rice-washing water,” with the aim of removing its oily content and reducing its drying nature—objectives that align with the modern processing method of stir-frying with wheat bran. Based on a comprehensive review of contemporary processing techniques, we recommend adopting the processing specification of “stir-fried Cangzhu with wheat bran.” Zhang Huamin stated that, while upholding the original intent of the classical formula and using current standards and regulations as a reference, it is essential to bridge the gap between historical textual records and contemporary norms. Drawing upon the current edition of the Chinese Pharmacopoeia and relevant processing guidelines, the selection should prioritize the herbal material and processing specifications that most closely correspond to the original source of the formula.

The State Administration of Traditional Chinese Medicine recently formulated the “Key Information Table for Classic Ancient Formulas (Seven Formulas) (Draft for Comments),” which includes seven classic ancient formulas such as Ling Gui Zhu Gan Tang and Wen Jing Tang. The State Administration of Traditional Chinese Medicine and the National Medical Products Administration have jointly organized experts to review and refine the key information, which will serve as an important basis for streamlining the registration and approval process of compound traditional Chinese medicine preparations derived from these classic ancient formulas.

Wang Yongyan argues that, in the verification of critical information, we must respect the laws of historical evolution, uphold tradition without being rigidly bound by the past, and adopt a developmental perspective to understand key common issues. We should both “revere the past” to ensure the clinical efficacy of time-honored classic formulas and “value the present” to meet the demands of modern large-scale production.

Li Yu, Director of the Science and Technology Department of the State Administration of Traditional Chinese Medicine, stated that the release of the principles for verifying key information on classic ancient formulas and the list of model formulas with key information is intended to resolve the technical challenges in the registration and review of compound preparations derived from these classics, provide reference for drug regulatory authorities in establishing review standards, and facilitate the effective implementation of the policy for streamlining the registration and approval process for such products.

Accelerate the revision and improvement of relevant supporting laws and regulations to ensure that time-honored classic prescriptions are translated into high-quality, effective medicines that meet the health needs of the general public.

Maxing Shigan Decoction, Shegan Mahuang Decoction, Xiaochaihu Decoction, and Wuling Powder are classic formulas recorded in the Treatise on Cold Damage and Miscellaneous Diseases. Ge Youwen, a specially appointed researcher at the China Academy of Traditional Chinese Medicine, has organically combined these four formulas and modified them to create a new formula—Qingfei Paidu Tang. According to Ge Youwen, “This formula is not formulated on the basis of individual herbs but rather on the basis of complete formulas; the formulas work synergistically with one another, so that, with the same total dosage of herbs, they produce several times the therapeutic effect.”

Qingfei Paidu Tang is a highly effective traditional Chinese medicine specifically formulated for the treatment of COVID-19, and it has been the most widely used and prescribed TCM formula in clinical practice. On March 26, the National Medical Products Administration granted clinical trial approval for Qingfei Paidu Tang. Under the existing drug review and approval system, however, it will still take some time for Qingfei Paidu Tang to be officially approved as a finished drug. To translate classic TCM formulas into commercially available medicines, a new approach is needed; the key lies in reforming the TCM drug review and approval mechanism.

Wang Jie, Chief Researcher at the China Academy of Traditional Chinese Medicine, has recommended that, drawing on the clinical experience of using Qingfei Paidu Tang to treat COVID-19, the registration and approval process for this formula be expedited, large-scale production be initiated as soon as possible, and the translation of this time-honored classical prescription into practical application be accelerated, so as to support routine epidemic prevention and control as well as socio-economic development.

In 2008, the former State Food and Drug Administration issued the Supplementary Provisions on the Registration Management of Traditional Chinese Medicines, and for more than a decade thereafter, there has been persistent calls to reform the review and approval mechanism for TCM. Both the former State Food and Drug Administration and the newly established National Medical Products Administration in 2018 have continuously revised these Supplementary Provisions. In October 2019, the Opinions of the CPC Central Committee and the State Council on Promoting the Inheritance, Innovation, and Development of TCM were released, providing fundamental guiding principles for the reform of the TCM registration system and ensuring that TCM remains true to its “Chinese” identity. On April 30 of this year, the National Medical Products Administration issued the Special Provisions on the Registration Management of Traditional Chinese Medicines (Draft for Comments), which introduces a new classification system for TCM registration, including innovative TCM drugs, improved-new TCM drugs, compound preparations of time-honored classic formulas, and drugs with the same name and same formula. The document explicitly establishes an evidence-based review and approval system for TCM registration that integrates traditional Chinese medicine theory, human-use experience, and clinical trials, while also introducing corresponding provisions for streamlined approval, priority review, conditional approval, and special approval tailored to the characteristics of TCM. A series of new ideas and measures have been introduced to simplify and optimize the review and approval process for TCM.

According to a responsible official from the National Medical Products Administration, the Special Provisions integrate existing human-use experience with traditional Chinese medicines into the review and approval evidence system for such products—a long-standing call from the industry and a strategic entry point for the drug regulatory authorities to actively explore and establish a technical evaluation system for review and approval that is tailored to the unique characteristics of traditional Chinese medicine.

Experts explain that the Special Provisions dedicate a specific chapter to clearly stipulating the evidentiary requirements for traditional Chinese medicine (TCM) use-experience data. Based on the extent to which such use-experience data supports the safety and efficacy of TCM products, appropriate reductions or exemptions may be granted in the corresponding registration submission materials. This clinically oriented approach should be integrated into regulatory decision-making for priority review of TCM products, embedded throughout the evidence-building process that links TCM theory, TCM use-experience data, and clinical trials, and applied in the assessment of the clinical value of TCM products. The Special Provisions further specify that, in the event of a public health emergency, TCM use-experience data may be utilized to grant special approval for expanding the approved indications and therapeutic uses of already-marketed TCM products. For drugs subject to the special approval procedure, following expert review and evaluation by the Center for Drug Evaluation of the National Medical Products Administration, their use may be restricted to a specified time frame and geographic scope in accordance with the particular needs of disease prevention and control.

At present, a major breakthrough has emerged in the approval process for Qingfei Paidu Tang. Recently, the National Medical Products Administration and the National Administration of Traditional Chinese Medicine have been working closely together to accelerate the translation of effective TCM formulas, including Qingfei Paidu Tang, into clinical practice. On the one hand, they are expediting the review and approval of manufacturing licenses to proactively prepare for a possible resurgence of COVID-19 during the autumn and winter seasons; on the other hand, drawing on this large-scale clinical application of TCM as a model, they are systematically synthesizing evidence of TCM’s therapeutic efficacy, objectively assessing the safety of TCM products, adhering to traditional principles while incorporating modern methodologies, and thereby paving the way for innovative applications of classic ancient formulas through adaptive modification and adaptation.

Wang Zhiyong stated that, at present, the translation of anti-epidemic proprietary medicines into clinical applications and the development of time-honored classic formulas are converging at a historic juncture, drawing widespread public attention and high expectations from the industry. It is therefore timely to reform and improve the review and approval mechanism for traditional Chinese medicines; relevant supporting laws and regulations should be promptly revised and refined to facilitate and ensure the transformation of classic formulas into high-quality, effective drugs, thereby meeting the health needs of the people and highlighting the unique value and advantages of TCM.