Traditional systems like Ayurveda , Siddha Vaidya and Unani has been practiced in India for centuries. Unfortunately, these practices have been relegated to “alternative medicinal sciences” when Allopathy came to our shores. Many reasons can be ascribed to this shift in primacy, the most significant being the inability or unwillingness of these sciences to subject themselves to the scrutiny of modern science, adopt modern manufacturing practices or use clinical testing based on “good clinical practices”.
Not unlike other early medicinal practices across the globe, formulations of these alternate Indian practices are botanical in origin. While Ayurveda, Siddha Vaidya and Unani are popular and have some franchise in India, there is a new development in the global field of pharmaceuticals that offers an opportunity for these alternative sciences to once again have global relevance.
New developments
The US Federal Drug Administration (FDA) has issued a new guideline for Botanical Drugs in June 2004. This is the third guideline after the ones provided for New Chemical Entities (early 1900’s) and Biological Drugs (1980’s).
A number of factors led to the issuance of this new guideline. Over the last decade, there has been a general “drying up” of pipelines of NCE companies. Further, newer therapies were required to combat disease like cancer that had emerged as the biggest killer in USA. The National Institute of Health (NIH) started federal funding of research for prospecting new therapies from Traditional Chinese Medicines (TCM) which showed promise as oncology drugs. The need to test TCM drug candidates, most of which are botanical in nature, in humans led to the need for new guidelines which were quite different from those existing for NCEs and Biologicals. To address this issue, US FDA came up with Botanical Drugs guideline.
With this new guideline, there is a clear route map to take a botanical poly-molecular drug candidate through the FDA process steps to achieve New Drug Approval (NDA) status as a prescription drug. As we all know, all drugs extracted from plant matter are poly-molecular in nature. US FDA not only recognizes this fact, but is willing to take documented evidence of use in other countries and cultures as compelling data worthy of consideration in its drug approval process. But it must be clearly understood that this is a new class of mainline therapeutic drug which is neither herbal nor alternative, as can be commonly perceived. There is a strong optimism that botanical drugs will not only open up avenues for new therapies for indications, but also use a slightly different process of discovery, one that will perhaps address few of the problems plaguing the drug industry today, such as the exorbitant cost of discovery, the extended time to market and the pressure of drying pipelines.
This new development led by US FDA represents a major opportunity for India because of the practice of Ayurveda, Unani and Siddha Vaidya for many thousands of years in our country. All of these traditional practices are based primarily on formulations derived from plant matter that are poly-molecular in nature. Hence, they are Botanical Drugs by US FDA definition. There is also documented evidence of use as well. In fact, Ayurveda, as currently practiced, is aimed at most major diseases ailing man today
While a major opportunity has presented itself for Ayurveda, there are significant challenges to be overcome, the most difficult hurdle being Chemistry & Manufacturing Control (CMC).
What is CMC?
Simply stated, there must be processes, checks and balances in not only the sourcing of raw materials, but also the subsequent manufacturing and quality control steps in order to reliably demonstrate standardization and reproducibility. For traditional practitioners of Ayurveda in India, many of whom make their own medicines, this is near nigh impossible. Even for large companies manufacturing Ayurvedic drugs, CMC as required by US FDA represents a major challenge.
Why is CMC difficult to achieve for producers of Ayurvedic drugs? Such companies obtain their plant raw materials from all over the place. It is well-known that because of the variability of weather, soil conditions, growing practices, use of fertilizers and pesticides, and even water quality, there is wide variations in how plants express the chemicals being extracted, not only in terms of the constituents, but also the composition of these constituents. Thus, the ability to manufacture a standardized product with batch-to-batch reproducibility is technically very difficult.
Other challenges
The second challenge is to develop drug formulations that have enough of the bioactive principals in the extracted mass to cause a physiological difference in humans when consumed. Currently, a formulation can be classified as Ayurvedic only if the extraction process employed uses water, milk or some edible oil. Again, it is well known that such traditional extraction media have limited ability to leach out the plant bioactives Powerful solvents currently not permitted by DCGI are needed. And if the rules are to be changed, it needs an act of legislation, which cannot happen unless there are spokesmen and lobby groups that can organize to bring about this legislation. Unfortunately, Ayurveda is almost a cottage industry and marshalling this group to bring about legislative change is nearly impossible.
Assuming one can bring about legislative change to use powerful solvents, the third challenge is that technology needs to be developed to ensure that residual levels of solvents in the final elute (solvent extraction mass) is below permissible levels as they can be extremely toxic and carcinogenic.
Finally, the new Botanical Drugs Guideline of US FDA does not dilute the rigour of how pre-clinical, toxicological and human clinical work is to be undertaken. This means a complete understanding of:
● Good Clinical Practices (GCP) and International Committee of Harmonization (ICH) guidelines
● Protocol development
● Use of independent CROs to validate studies and claims
● Use of randomized double blind placebo controlled studies and bio-statistical analysis of data.
Ayurveda research and drug production to date has not had the need to address any of these highly rigorous practices because the Indian DCGI regimen does not mandate any of these requirements as it does for Schedule Y drugs. And rightfully so . . . why would you want to prove something is safe and efficacious when it has been used for so many centuries – it merely adds to the cost of ayurveda medicine, which is used by the masses in India.
But, if Botanical drugs from India have to play a role in the global pharma space, many candidates can be developed from the existing Ayurveda etc. by following the US FDA guidelines. A major effort at upgrading research and manufacturing practices will be needed to address the challenges of CMC, of following modern drug development pathway to create evidence and scientific rationale regarding targets and mechanism of action, etc.
Opportunities
USA represents 45 per cent of the global market for drugs, which is estimated to be about $800 million in size. India is a mere fraction in size.
USA has recognized the need for Botanical Drugs as inherently they are “kinder and gentler” for addressing chronic diseases that require sustained medication. It is believed that Botanical Drugs will have less long-term toxicity with sustained use when compared to synthetic drugs. So, in the years to come, a new class of drugs, Botanical Drugs, will establish itself as a mainstream form of therapy, as legitimate as NCEs or Biologicals.
In this context of the above, India has the chance to address this huge market need. The nation not only has incredible plant bio-diversity, but has a long and rich tradition of Botanical Drugs (Ayurveda, Unani, etc.). Thus India is at the cusp of a major opportunity, which can be uncovered provided the issues highlighted above are addressed proactively:
By adopting modern technology needed for manufacturing, chemistry and analytical methods.
By being willing to subject Ayurveda to scientific rigour and scrutiny.
By bringing about legislative changes to redefine what is Ayurveda, perhaps to what US FDA considers to be Botanical Drugs.
These issues are very challenging and daunting. But they need to be addressed not only from the standpoint of a business opportunity, but also for the incredible sociological and ecological collateral benefits that will accrue to India. For example:
Collateral benefits:
If Botanical Drugs become mainstream, more land mass will be put to use to grow the plants needed. This increases green cover, which in turn reduces our carbon footprint.
Further, the rural economy will be uplifted because of the potential for higher income from plants grown for Botanical Drugs.
Finally, if agriculture becomes remunerative, perhaps it can help to reduce the migration of labour to urban centers.
Indeed, Botanical Drugs promises a major opportunity for India with far reaching implications.
-The author is Executive Director, Indus Biotech