India is emerging as a destination for outsourcing phytopharmaceuticals, herbal raw materials and processed herbs, oleoresins, volatile oils, natural perfumery compounds and natural colours. While phytopharmaceuticals can be put in a separate basket with active pharmaceutical ingredients (APIs), the rest constitute an emerging second basket. India's capability in phytopharmaceuticals has been established ever since India produced ephedrine and a number of alkaloids like belladonna alkaloids, reserpines, mono ammonium glycyrrhizinate (MAG), hyoscaymine, strychinine and cinchona alkaloids.
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This industry suffers from lack of promotions from the government, well defined good manufacturing practices that are specific to this sector, bench marks and protection by way of intellectual property rights. Other vexing issues include technological limitations in capability to analyse, high cost of investments and tedious and time consuming work to be done to get a "drug" status to the produce, except when the produce is already approved as a drug.
Availability of raw herbs is increasing and several farmers evince more interest in the cultivation of medicinal plants in place of traditional crops in one of the cycle per year. Encouragement from the National Medicinal Plants Board, set up by the government to develop agro-technologies, is of immense help. While there is a great opportunity for more phytocompounds to be developed from naturals, the effort and cost of developing them as drugs or cosmetic ingredients or for that matter nutraceutical ingredients are exorbitant and Indian industry has not taken it up in a big way. Given the vast knowledge of Ayurveda and the history of safe use that it has documented, the opportunity for such development for large number of health or cosmetics benefits are huge.
There has been a surge in producing a large number of standardised herbals/natural extracts, and this sector is fast becoming a "commodity market." Pharmaceutical technology adoption and innovation is happening very fast in this sector in an effort to beat the other producer and garner the market share. For example, what started as a simple Garcinia extract (an ingredient known for its weight management benefits for a dietary supplements usage as it is known to promote fat metabolism), manufacturers innovated to make it standardised Garcinia extract. They standardised it to (+) hydroxy citric acid content (HCA). Today suppliers boast of supplying up to 62 per cent w/w HCA content product. Similar is the story for Gymnema extract (known for its anti-diabetic effect) with high gymnemic acid contents and Boswellia extract.
In fact, there are at least a dozen manufacturers who produce high quality extracts in their own good manufacturing practices (GMP) complied factories. There are more than 50 manufacturers who claim they can supply quality extracts and phytocompounds probably relying on huge capacity and competencies available in the APIs sector. While syndicated data on the market size is not available on this sector, it is estimated to be significant. Unconfirmed reports put the figure at about Rs 1200 crore for what are referred to as "standardised extracts" and the figure would be higher if sales of pure phytocompounds used as drugs or drug intermediates are added.
All is not that well with this sector. It is facing difficulty to provide credible scientific data and information about such phytocompounds with regards to their safety and efficacies. More often the end user of phytocompounds wish to rely on the supplier for such support information in the form of dossiers, well characterised chemistry and composition of information on the herbal compounds, apart from safety information. Each end user would be willing to make a formulation of their own and hence will invest in generating efficacy data to claim support.
However, there seems to be reluctance on the user's part to generate safety information. Indian national laboratories must pitch in to prepare documentation on the safety data of priority herbs of Indian origin, replete with adequate and exhaustive history of use data. This would need to be strengthened with genotoxicity data, as history of use does not guarantee absence of genotoxicity and no international user would like to expose themselves to potential genotoxicity problems when they use these phytocompounds. Generation of this data is possible today adopting internationally accepted methods, which do not involve any animal testing. However, this is time consuming and expensive. Hence the Council of Scientific and Industrial Research (CSIR) laboratories and department of Ayush involved in promotion of this sector would do well to invest in this and generate such data on a priority list of herbs and its specified extracts/phytocompounds and make such data available to industry, even on subsided payment basis. This will promote growth of this sector and help garner a big market share internationally. Concurrently, this sector should innovate in producing novel and specific phytocompounds for health or cosmetics benefits from the vast ayurvedic actives and develop as a "specialty ingredient supplier."
The whole area of positive health benefits like heart health, improved digestion, sugar metabolism, weight management, diuretics, immunity boosters, liver protectors, energy boosters, iron absorption promoters, anti-oxidants, brain tonics, anti-ageing, wrinkle reducers, skin moisturers, anti-acne, anti-blemish, anti-psoriasis, anti dandruff, malodor inhibitors removers and anti-viral (herpes) is open for developing phytocompounds. Another important and stumbling block to the development of this sector is the absence of clearly defined guidelines/rules under the D&C Act for their evaluation and issue of approval as a drug. The current rule under D&C 122 A to D does not cover evaluation of phytocompounds for their approval as a drug. If the phytocompounds are pure compounds from plants then they can follow the Rule 122A for a new drug as per Schedule Y. However, no such clear section appears in the law giving specific requirements for a phytocompound or an extract to be evaluated for marketing authorisation as drug.
Key Indian herb extracts manufacturing players
● Chemiloids ,Vijayawada
● Natural Remedies Pvt. Ltd, Bangalore
● Sami Labs Ltd., Bangalore
● Synthite Ltd
● Amsar Pvt. Ltd., Mumbai
● Nisarg Biosciences Pvt. Ltd., Hyderabad
● Ayush Herbs Pvt. Ltd., Kangra (HP)
● Kisalaya Herbals Ltd.,Indore
● Reliance Life Science Pvt. Ltd., Mumbai
● Sanat Products Ltd., Delhi
● Konark Biosciences, Mumbai
Second basket of ayurvedic phytopharmaceuticals
India provides advantage due to its rich traditional knowledge and long history of use of many of these herbals from Ayurveda. Ayurvedic product's industry as well as herbal extract industry is growing, adopting modern pharmaceutical and food technologies for their production. This industry is also gearing to provide quality profiles of the extracts using current day analytical tools like TLC, HPLC and GC. Ayurvedic Pharmacopoeia Committee of the Government of India has just released the 6th volume standards for single herb ayurvedic raw materials as well as 1st volume of standards for compound recipes / poly herbal ayurvedic recipes. A compilation of the same in an electronic form with search engine is available from Central Council for Research in Ayurveda and Siddha (CCRAS). The ayurveda pharmacopoeia committee has just approved the use of excipients that are official in Indian pharmacopoeia, food laws as well as those approved by Bureau of Indian Standards. The same expert committee of ayurvedic pharmacopoeia has also recommended for regulatory approvals for all water extracts and hydro alcoholic extracts (Ethanol water - Ethanol up to 50%) to be recognised as ayurvedic extracts. Relevant notifications are expected soon from the department of Ayush, Ministry of Health. Both these will promote contemporisation, improved stability, better appeal and improved compliance and above all promote innovations. The Indian pharmacopoeia commission established about two years ago has also created a herbal products committee which has just finalised introduction of monographs on 32 Indian medicinal plants. The Indian pharmacopoeia monographs has mandatory identification test by TLC, and a mandatory assay for a marker compound by HPLC for each of the herbs. These have appeared in Indian pharmacopoeia 2007 edition which was released in December 2007. These monographs have in addition to standards provided new features by way of reproduction in IP 2007, colour photograph of plant part, use of botanical reference substances and chemical reference substance, TLC profiles and chromatograms for guidance of the user.
There has been a surge in the number of herbal and ayurvedic products that undergo safety and efficacy testing involving human volunteers/patients. CCRAS, the research wing of department of Ayush has begun an exercise to develop guidelines for human clinical trials on ayurvedic products. This will build both ethical and design guidelines for the same. The Ministry of Commerce's Export Inspection Council (EIC) has worked out "Level 1" quality certification parameters for ayurvedic products exported. These parameters involve permissible maximum limits for heavy metals, pesticide residues, microbial quality and aflotoxins. A voluntary certification scheme is expected to be notified regarding the same by Export Inspection Council soon. In order to tackle the problem of microbial quality levels in ayurvedic products, which is difficult to reduce to limits normally allowed in other categories of foods or products, the department of Ayush has also allowed low dose gamma radiation treatment as official method of the same. This decision is based on a study funded by the department and conducted by a national laboratory which found that such low dose gamma radiation treatment reduces effectively the microbial levels without affecting the properties of ayurvedic herbs and products. However, ayurvedic products will need to be labelled according to the laws of any importing country regarding the same.
The national biodiversity authority has begun to issue approvals and guidelines for implementation of the biodiversity law in India. A few research based pharmaceutical companies have begun either reverse pharmacology based NCE or product development using knowledge of Ayurveda. Likewise companies like Colgate, Unilever, Proctor & Gamble, Garnier, Perfiti and other international companies are also active in herbals area.
(The author heads the herbals research programme for Hindustan Unilever Research at Bangalore)