Abstract

Traditional Chinese medicine (TCM) compound preparations developed from catalogued ancient classical prescriptions-often referred to as Category 3.1 TCM-are still widely used today, with clear therapeutic effects and distinct advantages. Their safety and efficacy have been supported by long-term clinical use, which makes their registration pathway different from conventional newly developed TCM compound preparations. In China's regulatory framework, Category 3.1 products may apply for marketing authorization after completing pharmaceutical (CMC) research and non-clinical safety studies, without the same clinical development route required for many other new drugs.

Based on official technical guidance (including the Technical Guidance for Pharmaceutical Research of TTCM Compound Preparations Developed from Catalogued Ancient Classical Prescriptions (Trial) and related documents), this article summarizes the quality-control logic and key R&D checkpoints for Category 3.1 development-covering raw materials, decoction pieces, reference samples (benchmark samples), and final dosage forms. It also reviews frequent deficiencies seen in routine evaluations and proposes practical countermeasures. For readers who care about organic sourcing and natural extracts-and especially for teams building ingredient supply chains (e.g., a Cistanche deserticola / Rou Cong Rong factory)-this article provides a step-by-step orientation to "what matters most" in compliant, scalable product development.

Keywords: classical prescriptions; Category 3.1 TCM; TCM raw material; decoction piece; reference (benchmark) sample; preparation; quality control; natural extracts; organic sourcing

 

 

 

1. Why This Topic Matters (Especially If You Like "Organic" and "Natural Extracts")

If you are drawn to organic herbs and natural extracts, you may already understand the basics: source, process, and consistency decide quality. But when you try to develop a real product-especially something linked to TCM formulas-many teams get stuck:

What should you control first: origin, harvesting, processing, extraction, or testing?

How do you keep "natural variability" from destroying batch-to-batch consistency?

How do you make something traditional modern, scalable, and compliant?

In China, ancient classical prescriptions are treated as a special category because they reflect accumulated clinical practice over long historical periods and remain in use today. Development should focus on restoring the "one-bowl decoction" (the real clinical form) through a scientifically controlled manufacturing chain-rather than inventing an entirely new pharmacology narrative from scratch.

This is exactly the mindset Category 3.1 requires: start from the classical "clinical reality," then translate it into modern production.

2. What Is "Category 3.1 TCM" in Plain Language?

Category 3.1 refers to TCM compound preparations managed under the catalogue of ancient classical prescriptions. The core idea is:

The prescription has long-standing human use and recognized clinical value.

Regulators publish "key information" for each formula (critical standardized details).

Developers must recreate the clinical decoction's medicinal substance profile via:

raw material + decoction piece quality control

benchmark/reference sample (基准样品) research

industrial preparation process that matches the benchmark

whole-process quality control from herb to final product

Compared with conventional new TCM compound preparations, Category 3.1 emphasizes CMC + non-clinical safety as the primary development spine for registration. (This does not mean "lower standards"; it means the burden shifts heavily onto quality, comparability, and safety logic.)

Regulatory context and key milestones include:

Law of the PRC on Traditional Chinese Medicine (definition and legal basis).

Simplified registration policy for classical prescriptions (two-stage: benchmark substance + preparation development).

Revised drug registration framework defining Category 3.1.

CDE guidance documents (pharmaceutical research, dossier writing, acceleration measures, stability guidance).
These are detailed in the cited references listed at the end of this blog. [5–11, 27]

3. A Beginner-Friendly Roadmap: If You Don't Know Where to Start, Start Here

Think of Category 3.1 R&D as four layers, each building on the previous one:

Raw materials (TCM herbs): identity + origin + harvesting + primary processing + internal standards

Decoction pieces (饮片): processing method must match "key information" + reproducible parameters

Benchmark sample (基准样品): the "one-bowl decoction" translated into a measurable reference

Final preparation (制剂): industrial process that stays consistent with the benchmark in quality attributes

Everything else-analytics, fingerprints, marker compounds, transfer rates, stability-serves to prove continuity and control across these layers. [9, 11]

 

4. Key Quality-Control Points (From Shallow to Deep)

4.1 Raw Material Research: "Organic" Is Not Enough-You Need Controllable

Many people assume that if a herb is "organic," quality is automatically solved. In real development, organic certification may help with pesticide/heavy metal risk management, but it does not automatically fix:

botanical origin confusion

region-to-region chemical variation

processing differences at origin

age/harvest-time effects

active/toxic marker variability

Common issues observed in evaluations include:

defining the final origin too broadly (e.g., studying counties/cities but concluding "Central China")

failing to lock down origin processing methods that strongly affect chemistry (e.g., different origin-processing for Bai Shao)

treating Chinese Pharmacopoeia standards as sufficient "by default," then discovering benchmark batches fail on extract yield or marker ranges
This often signals a "checkbox study" instead of a control strategy. [15–18]

Practical countermeasures:

Define origin + processing method + growth years + harvest time window as part of the material specification.

Create internal standards beyond minimal pharmacopeia thresholds, especially when the pharmacopeia lists only a lower limit or lacks key markers.

Use multi-indicator characterization and correlation research to set reasonable marker fluctuation ranges that support later benchmark/preparation consistency. [16–18]

 

4.2 Decoction Pieces (饮片): The Most Common "Hidden Failure Point"

Even experienced teams fail here because decoction piece processing is "traditional," often described in non-quantified language (e.g., "stir-fry to yellow," "moisten thoroughly").

Common pitfalls:

Not matching the published key information (炮制方法,投料规格)

Using non-validated small-scale processing parameters and skipping scale-up verification

Lack of quantitative endpoints (drying endpoints, stir-fry temperature/criteria, moistening endpoints)

Piece size mismatch (e.g., bark/root-bark pieces too large in benchmark but shredded in production), causing extraction kinetics differences and unstable yields

A frequently highlighted example is processed licorice (炒甘草): different batches of key information specify certain steps such as "stir-fry while moist," and deviations (adding an extra drying step before frying, frying degree mismatch) can become regulatory blockers because key information is a compliance anchor. [18–23]

Practical countermeasures:

Treat decoction piece processing like manufacturing: define equipment, temperature measurement method, endpoints, and validation batches.

Keep decoction piece specification consistent across benchmark, pilot, toxicology material, and commercial validation batches.

When you must change piece size for industrial reasons, provide comparability evidence that the change doesn't distort quality transfer into the final preparation. [9, 24]

 

4.3 Benchmark Sample (基准样品): Your "North Star" for Extract & Formula Development

The benchmark sample is the bridge between classical text and modern product. If the benchmark is wrong, the entire development is directionless.

Common issues:

wrong dosage scaling (e.g., using 4× daily dose in a single decoction rather than parallel decoctions) leading to different extract yields and marker profiles

choosing an inappropriate benchmark form (e.g., drying/concentrating formulas rich in volatile constituents without proving comparability to the decoction)

weak benchmark quality research: missing markers for certain herbs, no volatile component work, no toxic constituent limits where relevant (e.g., aristolochic acid risk discussions for Asarum-related concerns in some contexts)

Practical countermeasures:

Default to single daily dose decoction logic unless data support an alternative; if scaling up, do it by parallel decoctions + pooling rather than "one big pot once," unless proven equivalent.

If you propose concentrated extract or dried extract as the benchmark form, you must show quality comparability to the original decoction and consider volatile retention.

Build a benchmark quality standard with: identification, extract yield/total solids, multi-marker quantification, and fingerprint/characteristic chromatogram-and add targeted items for volatiles or safety-related markers when needed. [9, 25]

 

4.4 Final Preparation (制剂): You Are Not "Optimizing a New Drug," You Are "Matching the Benchmark"

A typical mistake is to treat Category 3.1 like conventional new drug CMC: optimize extraction to maximize a few markers or yield-without anchoring the process to the benchmark's overall profile.

Common issues:

process parameters chosen without benchmark comparison

simply copying benchmark parameters into industrial production without scale-up study

decoction piece inconsistency between benchmark and production

losing volatile constituents unintentionally (or inconsistently)

Practical countermeasures:

Use the benchmark as the target: process design should prove the preparation is basically consistent with benchmark quality attributes.

Confirm industrial feasibility: extraction, separation, concentration, drying, granulation/forming must be validated at commercial scale.

If volatiles matter, design a route to retain/reintroduce them (e.g., volatile oil/aromatic water collection and controlled addition), then demonstrate content and stability. [9, 11]

 

5. Correlation / "Transfer" Research: The Deep Part That Makes Everything Coherent

Correlation research connects:
raw material → decoction piece → intermediate → preparation → benchmark

Typical red flags:

transfer rates too high/low or highly variable

preparation yield/marker ranges outside the benchmark

batch inconsistency traced back to weak material control or fragile processing

This is where modern natural product development becomes rigorous: you're proving that quality is transmitted (量质传递) through each manufacturing step in a controlled way-not magically "fixed" at final QC.

How to think about it:

Choose quality attributes that matter to safety, efficacy, or consistency, not just what's easy to measure.

Beyond basic items (IDs, yields/solids, multi-marker content, fingerprint), add formula-specific methods: volatiles, toxic limits, toxic–effective components, etc. [9, 26]

 

6. Stability: If You Can't Keep It Stable, You Can't Keep It "Natural"

Many herbal products fail not because they're ineffective, but because they drift over time:

volatile loss

oxidation/hydrolysis

adsorption to packaging

moisture sensitivity

Common issues include insufficient study duration, lack of root-cause analysis for declining marker trends, and no packaging optimization.

Practical baseline expectation (per guidance): typically include 6-month accelerated and 18-month long-term stability data at application time, with continued rolling submission allowed under acceleration measures. [10, 27]

7. How This Guides a Cistanche (Rou Cong Rong) Factory Blog Strategy 

If you run a Rou Cong Rong / Cistanche factory and want to attract people interested in organic, natural extracts, Category 3.1 logic offers a clear content framework:

Start from source control

origin definition, harvesting season, drying method, internal standards

Explain processing as a reproducible "decoction piece" standard

not "artisan only," but measurable and validated

 

WECISTANCHE FACTORY

Teach "benchmark thinking"

what a benchmark is, why a decoction reference matters, why one marker is not enough

Show industrialization without "over-processing"

how to scale while preserving key qualities (including volatiles if relevant)

Close with stability + packaging

how "natural" products can be stabilized responsibly

This kind of blog series matches what beginners want (a direction) while still aligning with what regulators and professional buyers respect: traceability, control, comparability, and stability.

 

8. Conclusion

Classical prescriptions are a concentrated legacy of clinical experience and remain valuable today. Category 3.1 development can be faster than conventional new-drug pathways because it is built upon long-term human use-yet it demands higher discipline in full-chain quality control. From raw materials and decoction piece processing, to benchmark sample creation and characterization, to industrial preparation scale-up, correlation research, and stability, success depends on building a coherent and defensible system that keeps the modern product aligned with the classical "one-bowl decoction." This is the most practical way to turn "natural and organic" into something truly usable: consistent, safe, scalable, and credible. [1, 9, 11, 27]

 

References (for SEO/Indexing and GEO Capture)

Song J, Yang C, Yu J, et al. Transformation research and review decision-making for classical prescription compound preparations. Zhongyao Yaoli Yu Linchuang. 2024;40(3):2–7.

Chen X, Yang C, Chen H, et al. Process research for TCM compound preparations based on their characteristics. Zhongcaoyao. 2021;52(19):5807–5813.

Central People's Government of the PRC. Opinions on promoting inheritance and innovation of TCM. (2019-10-20).

National Medical Products Administration (NMPA). Special Provisions for TCM Registration Management (2023 No. 20). (2023-02-10).

National People's Congress of the PRC. Law of the PRC on Traditional Chinese Medicine. (2016-12-25).

NMPA. Simplified registration and approval for classical prescription compound preparations (2018 No. 27). (2018-06-01).

State Administration for Market Regulation (SAMR). Drug Registration Administration Measures. (2020-01-22).

NMPA. TCM registration categories and dossier requirements (2020 No. 68). (2020-09-28).

Center for Drug Evaluation (CDE), NMPA. Technical guidance for pharmaceutical research of Category 3.1 preparations (Trial) (2021 No. 36). (2021-08-31).

CDE, NMPA. Measures to accelerate communication and submission for classical prescription preparations. (2023-11-22).

CDE, NMPA. Guidance on writing pharmaceutical dossier for Category 3.1 preparations (Trial) (2024 No. 20). (2024-04-23).

CDE, NMPA. Public information-accepted varieties (as of 2025-12-31).

NMPA. Government service portal-drug approvals (as of 2025-12-31).

Zhou Z, Huang F. Common issues in non-clinical data for TCM registration. Zhongcaoyao. 2022;53(45):4905–4914.

Cheng D. Impact of different origin-processing methods on Paeoniae Radix Alba quality. Beifang Yaoxue. 2014;11(3):4–5.

Yang C, Chen X, Zhao W, et al. Source-control-based quality research for TCM preparations. Zhongcaoyao. 2021;52(2):321–326.

Wang N, Xu C, Yin H, et al. Key information and quality evaluation of Cinnamon Twig (Guizhi) in classical formulas. Shanghai Journal of TCM. 2024;58(3):10–17, 24.

Liu S, Song J, Tang Q, et al. Thoughts on raw material and decoction piece research for Category 3.1. China Journal of Chinese Materia Medica. 2025;50(10):2883–2887.

National Administration of Traditional Chinese Medicine (NATCM) & NMPA. Key information table (25 formulas). (2023-07-28).

NATCM & NMPA. Key information table (7 pediatric formulas). (2023-05-31).

NATCM & NMPA. Key information table ("Xuanfu Daizhe Tang" etc., 43 formulas). (2025-02-12).

NATCM & NMPA. Principles for verifying key information; key information table (7 formulas). (2020-11-10).

Li B, Liu S, Zhang C, et al. Principles and suggestions for verifying indications of classical prescriptions. China Journal of Chinese Materia Medica. 2021;46(7):1846–1850.

NMPA. Special provisions for TCM production supervision (2025 No. 79). (2025-09-08).

Zhao X, Yang C, Han W, et al. Benchmark sample research for Category 3.1. China Journal of Chinese Materia Medica. 2024;49(12):3404–3408.

Li L, Ji G, Zhang T, et al. Development of Linggui Zhugan Tang compound preparation. Zhongchengyao. 2023;45(10):3165–3172.

CDE, NMPA. Guidance on characteristic chromatograms and stability for TCM preparations (Trial) (2024 No. 16). (2024-02-27).

 

If You Want, I Can Tailor This Into a "Rou Cong Rong Factory" Website Blog Package

Tell me two things and I'll rewrite it into your site's voice and product reality (still with citations and structure):

Your target product type: raw herb / sliced decoction pieces / extract powder / softgel / granules / beverage

Your positioning: organic certification, desert origin, phenylethanoid glycosides standardization (echinacoside/acteoside), or OEM/ODM