ReviewHerbal drugs: Standards and regulation
Graphical abstract
The present study attempts to identify the evolution of technical standards in manufacturing and the regulatory guideline development for commercialization of herbal drugs.
Introduction
The use of plants, parts of plants and isolated phytochemicals for the prevention and treatment of various health ailments has been in practice from time immemorial. It is estimated that about 25% of the drugs prescribed worldwide are derived from plants and 121 such active compounds are in use. Of the total 252 drugs in WHO's essential medicine list, 11% is exclusively of plant origin [1]. Nearly 80% of African and Asian population depends on traditional medicines for their primary healthcare [2]. In India, about 80% of the rural population uses medicinal herbs or indigenous systems of medicine [3]. About 960 plant species are used by the Indian herbal industry of which 178 are of high volume exceeding 100 metric tonnes a year [4]. Indian herbal market is registering a significant growth and is likely to reach Rs 145,000 million by 2012 and exports to Rs 90,000 million with a CAGR of 20% and 25% respectively (ASSOCHAM, 2008).
Based on nature of the active metabolites herbal drugs are of three types. Drugs used in crude form are the first category. The active constituents isolated after the processing of plant extracts represent the second category of herbal drugs. These are pure molecules and generally pharmacologically more active. The third type of herbal drugs for which data on acute and chronic toxicity studies in animals is available [5].
In 2003, a classification system for herbal drugs was recommended in the regional workshop on the regulation of the herbal medicines, organized by WHO regional office for South East Asia. Herbal drugs have been broadly categorized into four groups such as indigenous herbal medicines, herbal medicines in systems, modified herbal medicines and imported products with an herbal medicine base [6]. Indigenous herbal medicines are well known in terms of their composition, treatment and dosage due to their age old use in a local community. Herbal medicines in systems (Ayurveda, Unani and Siddha) have been in use for a long time and therefore, for local use assessments of efficacy are not required. Modified herbal medicines represent modification of the form of indigenous herbal medicine or herbal medicine in systems either in shape or dosage form, mode of administration, herbal medicinal ingredients, methods of preparation and medical indications. These should meet the national regulatory requirements of safety and efficacy. Pre-clinical data and clinical data may or may not be required depending on the modification(s). Imported herbal medicines (that include raw materials and products) must be registered and marketed in the countries of origin. Safety and efficacy data have to be submitted to the national authority of the importing country. Good manufacturing practices (GMP) compliance of the last two categories of herbal drugs is more critical. Apart from standardized herbal extract and raw material India is known to export herbal medicines in system such as ayurvedic drugs to different parts of the world. While there is increased usage of herbal drugs throughout the world, reports on side effects and adulteration of herbal drugs have raised concerns on their wide use and are affecting their commercialization. Further, regulatory procedures of these drugs are also not uniform across different countries. The present study attempts to identify development of technical standards in herbal drug manufacturing as well as the regulatory framework for commercialization of these drugs.
Section snippets
Effect of herbal drugs on human health: adulteration, heavy metal, pesticide and microbial contamination
Herbal products are not completely free from side effects. Well-controlled randomized clinical trials have revealed that undesirable side effects are possible in the use of herbal drugs. Cardiovascular problems with use of ephedra, hepatotoxicity by kava-kava consumption, anticholinergic effects leading to reduced visceral activity associated with asthma medicine containing Datura metel, water retention by liquorice are few examples of herbal drug side effects [7], [8]. Due to increased reports
Complexity and characterization: marker based analysis of herbal drugs
Herbal medicines have distinctive characteristics that make them different from synthetic drugs. They contain more than one active compound and the active principle is frequently unknown. For instance the Chinese medicinal plant Huang-qin (Scutellaria baicalensis) has over 2000 compounds [35].The chemical profiles of medicinal plants are affected by conditions of cultivation, manufacturing, marketing, and distribution. Physiological, genetic, and environmental variables (photoperiod, climate,
Regulatory norms development for herbal drugs
The first international recognition of the role of traditional medicine and use in primary health care was in The Declaration of Alma-Ata. It states, inter alia, that “…Primary health care relies, at local and referral levels, on health workers, including physicians, nurses, midwives, auxiliaries and community workers as applicable, as well as traditional practitioners as needed…” [42]. The safety problems emerging with herbal medicinal products are due to a largely unregulated growing market
International harmonization
Harmonizing efforts have been initiated on pharmacopoeial specifications, standardization and classification of herbal drugs to ensure uniformity of quality, safety and efficacy of the same herbal medicines across countries. The pharmacopoeias of Korea, Japan and China list similar herbal medicines, but their specifications are somewhat different. The same crude plant material may be described but the family or species of the original plant may be different. Further, the same crude plant
Conclusions
Advances in detection and quantitation of herbal drug components have increased the understanding of the relation between the specific component(s) and effects. There is a widespread concern on the unintended/harmful effects of herbal drugs with greater number of studies carried out on herbal drug reactions in the developed countries. This is challenging the notion that long traditional use is an indication for safety of herbal medicines. Manufacturers, particularly in South East Asia, face the
Conflict of interest statement
We have no conflicts of interest that are directly relevant to the content of this review.
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