Guideline Number: [Z]GPH1-1
Technical Guidelines for Pretreatment of Raw Materials of Traditional Chinese Medicine and Natural Drugs
(Draft 2)
March 18, 002
Technical Guidelines for Pre-processing of Raw Materials in Traditional Chinese Medicine and Natural Medicines
Overview
This guidance provides technical direction for the pretreatment of raw materials in registration applications for traditional Chinese medicines and natural drugs.
The raw materials for traditional Chinese medicine (TCM) and natural drug preparations include Chinese medicinal herbs, processed TCM slices, extracts, and active ingredients. To ensure the scientific validity, efficacy, safety, and controllability of new TCM drugs, necessary pre-treatment of raw materials is required. Pre-treatment involves identification and testing, as well as processing and refinement of the raw materials.
Basic Content
I. Raw Material Identification and Inspection
There is a wide variety of Chinese herbal medicines with complex sources. Even for the same species, quality can vary significantly due to differences in origin, ecological environment, cultivation techniques, and processing methods. Additionally, raw materials such as Chinese medicine extracts and active ingredients may also present quality issues. To ensure accurate dosing and uniform product quality, all raw materials used in formulations must be identified and tested. Only materials that pass inspection should be used in production.
The identification and testing of raw materials are based on statutory standards. Current statutory standards include the Pharmacopoeia of the People's Republic of China, Ministry (Bureau) standards, and provincial, municipal, or autonomous region standards. If standards are revised, the revised versions must be followed. For example, the 2015 edition of the Chinese Pharmacopoeia defines Schisandra chinensis as the dried ripe fruit of Schisandra chinensis (Turcz.) Baill. or S. sphenanthera Rehd. et Wils., both belonging to the family Magnoliaceae, referred to as "Northern Schisandra" and "Southern Schisandra," respectively. The 2020 edition lists only Schisandra chinensis (Turcz.) Baill. under the Schisandra entry, while separately designating the fruit of S. sphenanthera Rehd. et Wils. as "Southern Schisandra." Therefore, when the medicinal name is specified as "Schisandra," it refers exclusively to Northern Schisandra.
If raw materials without established standards are used, quality standards for these materials must be defined, and they shall be identified and tested in accordance with those standards.
For Chinese medicinal materials sourced from multiple origins, in addition to meeting quality standards, the variety should generally be fixed. For varieties with significant quality differences—such as Pueraria lobata (Ge Gen), which includes Fenge and Fenge types where flavonoid content can differ by several to over ten times—the specific variety must be fixed, and justification for its selection must be provided. When quality varies significantly by origin—for example, Salvia miltiorrhiza (Danshen) from different regions showing marked differences in salvianolic acid content—the geographic origin should be fixed. Similarly, when quality changes noticeably based on harvest time, the harvest period must be carefully controlled.
If the raw material quality standard is too simple to meet the requirements for new drug research, developers should refine the standard themselves. If the herb standard does not include an assay for components measured in the formulation, developers must establish an assay method and set specification limits, ensuring these limits align with the actual characteristics of the raw material. The refined standard can serve as an internal enterprise control standard. For example, current standards for Salvia miltiorrhiza do not include an assay for water-soluble components. If such an assay is established in the formulation, it must also be included in the internal control standard for the Salvia miltiorrhiza herb.
Self-testing reports must be provided for toxic medicinal materials; the legality of source must be ensured for materials derived from endangered species.
II. Processing and Preparation of Medicinal Herbs
Medicinal materials often contain impurities such as mud, ash, and non-medicinal parts; they may also be contaminated with moldy or insect-damaged items. Additionally, Chinese herbal medicines have complex compositions, with many herbs offering multiple therapeutic effects. Appropriate processing methods should be selected based on the intended indications. Processing can enhance certain effects, reduce others, or even eliminate them entirely, thereby altering the herb's properties to meet prescription requirements.
Processing is closely linked to formulation production. Most raw materials must undergo processing before being used in finished pharmaceutical products. Therefore, after completing identification, herbs should be processed according to formula requirements, material characteristics, and extraction needs. Common processing steps include cleaning (purification), slicing, frying/roasting, and grinding.
(I) Cleaning
Purification is the initial processing step for medicinal herbs. This process removes impurities to ensure the herbs meet pharmaceutical standards. Herbs that have undergone purification are referred to as "purified herbs." Common methods include sorting, winnowing, washing, sieving, trimming, cutting, scraping, shaving, discarding, brushing, rubbing, grinding, pounding, extracting, and pressing.
(II) Slicing
Slicing refers to cutting processed medicinal materials into slices, segments, blocks, or other forms suitable for production. The type and specifications should be determined by considering the material's texture, processing methods, and extraction processes for formulations. Except for a few fresh or dry-cut herbs, most require softening treatment to facilitate slicing. During softening, factors such as time, water absorption, and temperature must be controlled to prevent loss or degradation of active ingredients.
(III) Processing
Refers to the processing of medicinal materials after cleaning and slicing, using methods such as firing, water treatment, or combined fire-water treatment. Common techniques include stir-frying, honey-roasting, moxibustion, calcination, steaming, boiling, scalding, stewing, compounding, and levigation. Processing methods must comply with national standards or regional processing regulations established by provinces, municipalities, or autonomous regions. For special processing requirements, custom processing methods and product specifications must be developed, supported by relevant research data. Customized processing methods should ensure scientific validity and feasibility.
(IV) Crushing
Refers to grinding medicinal materials into coarse, medium, or fine powders. The particle size should be determined based on the requirements of formulation production. Hard and difficult-to-cut medicinal materials are generally ground before extraction; some precious materials are ground into fine powder for direct use to prevent loss; others are ground into fine powder to aid in formulation shaping, serving as a excipient. Ground medicinal materials must specify the particle size, the rationale behind it, and the yield rate. For materials containing volatile components, control the grinding temperature. For soft materials with high sugar or gum content, select an appropriate grinding method. Toxic materials must be ground separately.
References
1 National Medical Products Administration "Pharmacopoeia of the People's Republic of China" 2000 Edition
2, Ministry of Health Drug Administration, "Guidelines for Pharmaceutical Research on New Chinese Medicines" 1993
3: Technical Requirements for Research on New Traditional Chinese Medicine Drugs, National Medical Products Administration
[Authors] Research Group on "Guiding Principles for Pre-treatment of Raw Materials of Traditional Chinese Medicine and Natural Drugs"