WHO/ICH Guidelines, Patenting & Regulatory Issues for Herbal Drugs
This unit covers the regulatory and intellectual property framework for herbal medicines: (1) WHO and ICH guidelines for the quality assessment and stability testing of herbal drugs. (2) Patenting and IPR — definitions (Patent, IPR, Biopiracy, Bioprospecting), and the landmark Turmeric and Neem patent case studies that shaped India’s approach to protecting traditional knowledge. (3) Regulatory framework in India — the ASU DTAB, ASU DCC, and Schedule Z of the Drugs & Cosmetics Act governing manufacture of Ayurvedic, Siddha, and Unani drugs.
Syllabus & Topics
- 1WHO Guidelines for Herbal Drug Assessment: WHO published ‘Quality Control Methods for Herbal Materials’ (2011) and ‘WHO Guidelines on GACP of Medicinal Plants’ (2003). Quality parameters: (1) Identity (macroscopic, microscopic, TLC fingerprint). (2) Purity (foreign matter ≤2%, ash values, acid-insoluble ash, heavy metals, pesticide residues, aflatoxins, microbial limits). (3) Content/Assay (quantitative determination of active markers by HPLC/GC). (4) Stability. WHO monographs available for 120+ medicinal plants. Also: WHO Traditional Medicine Strategy 2014-2023.
- 2ICH Guidelines for Herbal Drugs: ICH (International Council for Harmonisation) Q1A-Q1F: Stability testing guidelines. Applied to herbal drugs: ICH Q1A (R2): General principles — study design, conditions, testing frequency. Q1B: Photostability testing. For herbal drugs: Test parameters: appearance, color, odor, moisture, assay of markers, microbial limits, TLC fingerprint, dissolution (for solid forms). Conditions: Long-term (25°C/60% RH, 12 months min), Accelerated (40°C/75% RH, 6 months), Intermediate (30°C/65% RH). Shelf life assignment based on stability data.
- 3Stability Testing of Herbal Drugs – Challenges: Herbal drugs are complex mixtures → stability of individual markers may not represent stability of the entire extract. Challenges: (1) Multiple active components (synergistic effects — all must remain stable). (2) Degradation products may be unknown. (3) Physical instability (color change, sedimentation). (4) Microbial contamination (natural products are good growth media). (5) Moisture sensitivity (hygroscopic extracts). Solutions: fingerprint chromatography (HPTLC/HPLC), accelerated stability studies, packaging optimization.
- 4Patenting – Key Definitions: Patent: exclusive right granted by government to an inventor for a limited period (20 years from filing) to prevent others from making, using, selling the invention. In exchange, inventor discloses the invention (public knowledge). IPR (Intellectual Property Rights): umbrella term covering Patents, Trademarks, Copyrights, Trade Secrets, Geographical Indications, Plant Variety Protection. Farmers’ Rights: right of farmers to save, use, sow, re-sow, exchange, and sell seeds (protected under Plant Variety Protection & Farmers’ Rights Act, India, 2001).
- 5Bioprospecting & Biopiracy: Bioprospecting: systematic search for, and development of new sources of chemical compounds, genes, proteins, and organisms from biodiversity for commercial purposes. When done ethically (with prior informed consent + benefit sharing) → legitimate. Biopiracy: appropriation of traditional knowledge or biological resources WITHOUT prior informed consent of indigenous communities or benefit sharing. Unethical and illegal under CBD (Convention on Biological Diversity) and Nagoya Protocol. India: Biological Diversity Act 2002 → National Biodiversity Authority (NBA) regulates access.
- 6Turmeric Patent Case (1995-1997): US Patent 5,401,504 (March 1995): granted to University of Mississippi Medical Center for ‘Use of Turmeric in Wound Healing.’ CSIR (India) challenged the patent at USPTO (US Patent and Trademark Office). Argument: Turmeric’s wound healing property is traditional knowledge documented in ancient Ayurvedic texts (Sushruta Samhita), Sanskrit texts, and even a 1953 journal article. Result: Patent REVOKED in August 1997 (prior art established). Significance: First time a traditional knowledge-based patent was successfully challenged. Led to India creating TKDL.
- 7Neem Patent Case (1995-2005): European Patent EP 0436 257 B1 (1994): granted to W.R. Grace Company (USA) + USDA for ‘Method for controlling fungi on plants by aid of hydrophobic extracted Neem oil.’ Challenged by: International Federation of Organic Agriculture (IFOAM), Government of India, Research Foundation for Science, Technology and Ecology. Argument: Neem’s antifungal properties known in India for centuries (prior art — documented in multiple Indian texts). Result: Patent REVOKED in 2005 by European Patent Office (EPO). Significance: 10-year battle → demonstrated difficulties in challenging biopiracy, strengthened case for TKDL.
- 8TKDL (Traditional Knowledge Digital Library): Created by CSIR + AYUSH Ministry (2001). Digitizes traditional Indian knowledge from Ayurveda, Siddha, Unani, Yoga texts in patent-compatible format. Available in 5 languages (English, French, German, Spanish, Japanese). Contains 3.6 lakh formulations. Purpose: acts as ‘prior art’ searchable database for patent examiners at USPTO, EPO, JPO → prevents granting of patents on existing traditional knowledge. Access agreements signed with 13 international patent offices.
- 9Regulatory Issues – India: AYUSH drugs (Ayurveda, Yoga & Naturopathy, Unani, Siddha, Homeopathy) regulated under Chapter IVA of D&C Act 1940. ASU DTAB (Ayurveda, Siddha, Unani Drugs Technical Advisory Board) – Section 33C: advisory body for ASU drug standards. ASU DCC (Drugs Consultative Committee for ASU) – Section 33D: coordinates uniform administration between Central and State governments. AYUSH Ministry (est. 2014, formerly Dept of AYUSH): overall policy, regulation, education, research.
- 10Schedule Z of D&C Act: Schedule Z governs the manufacture of ASU drugs. Requirements: (1) Manufacturing license from State Licensing Authority. (2) Compliance with Schedule T (GMP for ISM). (3) Qualified Vaidya/Hakim/Siddha physician in charge. (4) Raw materials must meet Ayurvedic Pharmacopoeia of India (API) / UNANI / Siddha Pharmacopoeia standards. (5) Formulations must be as per classical texts (Authoritative Books listed in First Schedule to D&C Act — Charaka Samhita, Sharangdhara Samhita, Bhaishajya Ratnavali, etc.). For proprietary ASU medicines: must list ingredients, must not contain scheduled drugs from allopathic system.
- 11Recent Regulatory Developments: AYUSH Mark: quality certification for ASU products (voluntary). Pharmacovigilance for ASU drugs: AYUSH pharmacovigilance program under All India Institute of Ayurveda, New Delhi. FSSAI regulations for herbal supplements: Health Supplements, Nutraceuticals, Foods for Special Dietary Uses, and Special Medical Purposes (Regulations 2016). Export quality: WHO-GMP certification required for ASU drug exporters. Quality issues being addressed: heavy metal contamination in Bhasmas, microbial contamination, aflatoxins in herbal raw materials.
Learning Objectives
Exam Prep Questions
Q1. What is the significance of the Turmeric patent case?
The Turmeric patent case (1997) was the first instance where a patent based on traditional knowledge was successfully challenged and revoked. The U.S. Patent and Trademark Office had granted a patent for the use of turmeric in wound healing, but India’s Council of Scientific and Industrial Research (CSIR) proved that this knowledge already existed in ancient Ayurvedic texts and traditional practices. The case established that traditional knowledge constitutes prior art and cannot be patented as a novel invention. It also demonstrated that developing countries can legally challenge unjust patents. This case led to the creation of India’s Traditional Knowledge Digital Library (TKDL), which documents traditional medicinal knowledge to prevent biopiracy and has helped block hundreds of such patent applications worldwide.
Q2. What is the difference between Bioprospecting and Biopiracy?
Bioprospecting refers to the legal and ethical exploration of biodiversity to discover commercially valuable biological compounds, such as new drugs, enzymes, or genetic resources. It is conducted with prior informed consent (PIC) from local communities and under mutually agreed terms (MAT) that ensure fair benefit-sharing. These practices are governed by international agreements such as the Convention on Biological Diversity (CBD) and the Nagoya Protocol.
Biopiracy, in contrast, refers to the unauthorized exploitation of biological resources or traditional knowledge without consent or benefit-sharing with the indigenous communities or countries from which the resources originate. It often involves companies or researchers patenting biological materials or traditional medicinal knowledge from biodiversity-rich developing countries without acknowledging or compensating the original knowledge holders.
Q3. What are the key quality parameters tested for herbal drugs as per WHO?
The World Health Organization (WHO) recommends several quality control parameters for herbal drugs to ensure their safety, identity, and efficacy. These parameters are broadly categorized into identity, purity, and content tests.
Identity testing includes macroscopic examination (appearance, color, odor, taste), microscopic evaluation (presence of characteristic tissues such as trichomes and starch grains), chromatographic fingerprinting using techniques like TLC or HPTLC, and molecular identification methods such as DNA barcoding.
Purity testing ensures the absence of contaminants and includes limits for foreign matter (usually less than 2%), total ash, acid-insoluble ash, water-soluble extractive value, alcohol-soluble extractive value, moisture content (generally less than 10%), heavy metal limits (lead <10 ppm, cadmium <0.3 ppm, mercury <0.5 ppm, arsenic <5 ppm), pesticide residues, aflatoxin limits (B1 <2 ppb), and microbial contamination (total aerobic count with absence of pathogens such as E. coli and Salmonella).
Content evaluation involves quantitative determination of active constituents or marker compounds using validated analytical techniques such as HPLC, GC, or spectrophotometry to ensure batch-to-batch consistency and therapeutic efficacy.