Quality control of Medicinal plants

6/15/2014

Capacity building training on quality standards to manufacture of traditional herbal medicine in Nepal Organized by: Department of Pharmacy, Kathmandu University, Nepal June 11-13, 2014

Part 1 Quality Risks of Medicinal Plants (MPs) and Herbal Medicinal Products (HMPs)

QUALITY CONCERNS OF HERBAL MEDICINAL PRODUCTS Namraj Dhami Assistant Professor, Pharmacognosy School of Health and Allied Sciences Pokhara University, Nepal

Part 2 Regulatory Initiatives on Quality Control of Medicinal Plants and Herbal Medicinal Products

Conventional vs. Herbal medicines

Plants in Medicine: the facts 2.

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Serving human society since antiquity Ayurveda, Traditional Chinese and other traditional systems of medicines evolved from the traditional use of medicinal herbs Global plant diversity estimate go beyond 550,000 species with flowering plants is nearly 350,000 with the probability of increasing by 10-20% (www.theplantlist.org) About 30% (nearly 30,000 to 85,000) plants possess therapeutic potential Herbal Medicinal Products (HMPs) exclusively contain plants and / or plant products More than 25% modern medicines come from plants Adoption of herbal products increasing worldwide Rigorous quality control frameworks functioning worldwide Cases of adverse effects also increasing © N Dhami, Pokhara University Nepal 2014

Pictures taken from different websites for academic use only

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The quality promises of HMPs

Pure bioactive compounds

Raw plant material

Crude drugs

© N Dhami, Pokhara University Nepal 2014

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Determinants of quality of HMPs Quality and quantity of chemical entities

Safety Without adverse effects

Purity

Genomic composition Developmental stage Ambient environment Cultivation practices Harvesting practices

Without unnecessary ingredients

Potency (efficacy) Effective to cure the concerned health condition

Consistency

Postharvest processing Storage conditions Adulterations Pesticide accumulation Microbial contaminations

Similar (identical) product profile for all Spatio-temporal variation in chemical profile thereby variation in therapeutic response is common phenomenon in medicinal plants. © N Dhami, Pokhara University Nepal 2014

Namraj Dhami - WHO GMP Training, School of Health and Allied Sciences Pokhara University, July 5-6, 2013

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Case 1

Quality risks of HMPs

The most common adulterants or contaminants: Dust, pollens, insects, rodents, parasites, microbes, fungi, mould, toxins, pesticides, toxic heavy metals and/or prescription drugs. The most severe adverse effects caused adulterations: Agranulocytosis, meningitis, multi-organ failure, perinatal stroke, arsenic, lead or mercury poisoning, malignancies or carcinomas, hepatic encephalopathy, hepatorenal syndrome, nephrotoxicity, rhabdomyolysis, metabolic acidosis, renal or liver failure, cerebral edema, coma, intracerebral haemorrhage, and death. © N Dhami, Pokhara University Nepal 2014

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Case 2 Case 3

Product substitution occurred in 30/44 of the products tested Only 2/12 companies had products without any substitution, contamination or fillers.

Organochlorine: DDT, aldrin, dieldrin and endrin Organophosphorus: malathion, parathion and diazinon Carbamate and triazine compounds


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Health hazards caused by pesticides

Case 4

Carcinogenic: 2,4 dichlorophenoxy acetic acid (2,4-D, triazines, endrin, linuron, rotenone, captan and maleic hydrazide Teratogenic: Cyanazine, carbaryl, endrin, rotenone, and benomyl Mutagenic: Dillate, trifluralin, dimethoate, carbaryl, rotenone, benomyl and maleic hydrazide, Neurotoxic: Ethyl(p- nitrophenyl)thiobenzene phosphate (EPN) Reproduction interfering: Dibromochloropropane (DBCP), dimethoate, rotenone and benomyl

2,4 dichlorophenoxy) acetic acid (2,4-D), dicamba, parathion and carbofuran included in the highly toxic class (LD50 0–50 mg/kg) © N Dhami, Pokhara University Nepal 2014

Namraj Dhami - WHO GMP Training, School of Health and Allied Sciences Pokhara University, July 5-6, 2013

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Ninety-one samples labeled as 58 distinct products originated / manufactured in United States (n = 62), apparently Asian (n = 15), and not clearly identified (n = 14). Although no sample claimed to include synthetic substances, 74 (81%) contained PDE5-inhibitor pharmaceutical ingredients, including tadalafil and/or sildenafil (n = 40, of which 18 contained >110% of the highest approved drug product strength) or PDE5-inhibitor analogs (n = 34). © N Dhami, Pokhara University Nepal 2014

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Case 5

Case 6

Native Australian fruit, contains phenolics (505.2 to 376.1 mg GA E/g DW) Tannins and ellagic acid are the major phenolic compounds The levels of ellagic acid varied from 140.2 to 30.5 mg/g DW Vitamin C (322.2 to 173.5 mg/g DW) Antioxidant capacities (FRAP: 5030.5 to 4244.9 µmol Fe2+/g DW; ORAC: 3861.5 to 2985.6 µmol Trolox E/g DW) The levels of sugars varied from 619.0 to 130.0 mg Glu E/g DW)

428 published articles assessed from Journal of Ethnopharmacology and Phytomedicine Out of 428 articles 308 (72%) cited plant names incorrectly 9,178 scientific names cited of which 3,445 (38%) names were incorrect Big challenge for harmonizing the application of botanical nomenclature system for all, especially in natural product chemistry, pharmaceutical and allied streams © N Dhami, Pokhara University Nepal 2014

There are ample of reports on spatio-temporal phytochemical variation in different geo-biological samples of medicinal plants.

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The hidden Health Risks: Ginkgo biloba is no more safe GB: One of the most sold and rigorously researched medicinal plants GB based HMPs commonly used in the treatment or prevention of cardiovascular and cerebrovascular dysfunction Common alternative for dementia and cognitive impairments especially Alzheimer’s.

Case 7 March 2013 Toxicology and carcinogenesis studies of Ginkgo biloba extract (CAS No. 90045-36-6) in F344/N rats and B6C3F1/N mice © N Dhami, Pokhara University Nepal 2014

Remarkable phytochemical variation found in different GB samples Ingredients

Shangai China GB

EGb 761

Flavone glycosides

31.2%

24%

Terpene lactones

15.4%

6%

Bilobalide

6.94%

2.6-3.2%

Ginkgolide A

3.74%

Ginkgolide B

1.62%

Ginkgolide C

3.06%

Ginkgolic acid

10.45 ppm

Case 8 “Acute Hepatitis and Liver Failure Following the Use of a Dietary Supplement (OxyELITE Pro) Intended for Weight Loss or Muscle Building” - May - October 2013

2.8-3.4%