Phytopharmaceutical: an Emerging Platform

Dr. Ashwini Kumar
CliniExperts Services Private Limited
Globally, herbal medicine has been considered an important alternative to modern allopathic medicine. Herbal medicines are very popular throughout the globe, however, only a few medicinal herbs have been scientifically evaluated for their potential in medical treatment. In most countries, the herbal drugs are poorly regulated and are of ten neither registered nor controlled by the health authorities. In India, plant based products used as medicines come under the category of Phytopharmaceuticals. They include Ayurvedic, Siddha, Unani(ASU) Drugs and any other plant based product which is used as medicine. The phytopharmaceuticals are under the purview of the Central Drugs Standards Control Organization (CDSCO).

Dr. Ashwini Kumar, CEO of CliniExperts Services Private Limited , which provides end-to-end regulatory services to Domestic & International pharmaceutical markets has a total commitment to medical research and its significance to the world of tomorrow. Dr. Kumar in his interview with PBW talks about Phytopharmaceutical market across the world with a focus on India.

CliniExperts is a complete product pipeline development partner for Phytopharmaceutical companies developing and commercializing drug products and offers end-to-end solution for Phytopharmaceutical Drugs need. Please give us an insight into the Phytopharmaceutical industry across the world with a focus on India.

Before elaborating on the phytopharmaceutical drugs in India, I would like to inform, that this is the newest division declared by Indian FDA (CDSCO) after AYUSH, & the division is still getting evolved in terms of setting up standards & guidance documents.

For a drug to be in Phytopharmaceutical category, the basic mandate is, it must include purified and standardized fraction with defined minimum four bio-active or phyto-chemical compounds (qualitatively and quantitatively assessed) of an extract of a medicinal plant or its part, for internal or external use of human beings or animals for diagnosis, treatment, mitigation or prevention of any disease or disorder but does not include administration by parenteral route. Phytopharmaceutical class of drugs have origin in traditional system of medicine as well as phytomedicine.

The modern age may have sovereignty of synthetic drugs however phytomedicine is making a strong and dramatic comeback. The popularity of AYUSH systems of medicine is growing at a rapid pace due to its effectiveness with sound efficacy, we all should be very thankful to CDSCO for regulating the category under AYUSH & Phytopharmaceuticals.

Globally all the countries are now regulating the category in the same manner under Traditional Medicines. China has already established as top leader of the herbal market, but if we talk about India, we have an additional benefit if having the category defined under pharmacopoeial standards as Ayurvedic Pharmacopoeia. We all should feel very lucky that we had all these herbal(Ayurvedic) medicines standardized centuries ago with proven safety and efficacy.

In India, the interest of pharmaceutical industries towards medicinal plants is increased in last decade, and this is because of increased awareness and interest in medicinal plants by public and the scientific community. Here has been rising interest in herbal drugs, with many players of domestic origin like Patanjali, Dabur, Hamdard, Baidnath, Himalaya and even international players like Herbalife, & Boinorica are also investigating the commercial potential of their herbal products in India. In 2017, the global market for plant-derived drugs grew from $29.4 billion to around $39.6 billion and it is assumed that by 2022 with a compound annual growth rate (CAGR) of 6.1% for the period of 2017-2022.

From the Indian market perspective, phytopharmaceutical is an emerging platform. Majority of the ayurvedic pharmacies are not conversant with the emerging market for phytopharmaceuticals. Standardized extracts derived from Commiphora guggul, Ginkgo biloba, Silybum marianum and Zingiber officinale are few examples representing herbal class of drugs in Indian market. The above mentioned standardized herbal extracts are widely prescribed by practitioners of allopathic divisions also.

Herbal medicines are very popular throughout the globe, however, only a few medicinal herbs have been scientifically evaluated for their potential in medical treatment. India has a rich history herbal medicines, so do you think India has a potential Phytopharmaceutical industry in the making?

We do have to accept that with the bang of Allopathic formulations in the Indian market it was very widely accepted by the authorities as well as the end user also and this was just because of the rapid action of the synthetic drugs on the disease and/or disorder state of the patient, which is the very prime objective of the treatment, and the adverse effects we of the formulations are not playing a major role their approval.

But we are aware of the Supreme Court's ruling which had declared a number of synthetic (allopathic) formulations as irrational and this is just because of the evolution of the CDSCO with the new stringent requirements for the approval.

Along with this the technology is also evolving at a great pace with help us in justifying the equivalency between the allopathic & herbal formulations and that to without the adverse effects. Means only pros & no cons and who does not require in this manner.

Just because of this only there is growing demand for herbal medicine in the developed as well as developing countries like India, because of their wide biological activities, higher safety of margin than the synthetic drugs and yes obviously at a comparatively lesser costs.

The market of formulations or medicine originating from medicinal plants or natural products is largely based on prescription of around 5 lacs (INDIAN TRADITIONAL, AYUSH and INTEGRATED) practitioners practicing independently and in approximately 3000 hospitals. It has been observed that majority of the Ayurveda practitioners prescribe classical or patent and proprietary medicines in clinical practice. Their knowledge about use of standardized herbal extracts-based formulations is very limited.

As per one estimate, 1300 medicinal plants are used for medicinal purpose. In Ayurveda itself, several drugs have established role in treatment of liver diseases. Picrorrhiza kurroa, Andrographis paniculata, Solanum nigrum, Eclipta alba and Cicohrium intybus are few to mention. The need of the hour is to bring scientifically established herbal drugs under the umbrella of phytopharmaceuticals.

Further, it is expected that in coming days, herbal market shall be governed by supercritical extracts owing to improved bioavailability, reduced toxicity and improved dosage form. Nanophytomedicine is also knocking door of the pharmaceutical industry. In near future, supercritical extracts, nonophytomedicine and phytopharmaceuticals may be seen as driving force of the herbal industry.

The CDSCO has released a draft regulation, as an amendment to the Drugs & Cosmetic Rules 1945, which defines and outlines regulations for Phytopharmaceuticals. How challenging is the development of new Phytopharmaceuticals?

If we talk about the regulations of the Phytopharmaceuticals defined by the CDSCO, yes they are a bit more stringent than AYUSH because the safety and efficacy of the Herbal & Ayurvedic formulations registered under the AYUSH is considered as already safe & sound because they are already proven in the related pharmacopoeias identified by AYUSH, but when talk about the Phytopharmaceutical standard, they are very much equivalent to Allopathic formations like orals, biologicals etc. thus one needs to very stringently define the safety & efficacy as per the guidelines set by CDSCO, which takes a lot of time & money to be invested.

& there are very rare chances of waivers to be given in the process so as to set & define a standard of the formulation which can also be considered by the authorities for the companies seeking approval of the same or relative formulation in the future. In other words we can say that we are in the process of setting up a strong base for the future formulations.

How are new herbal medicines placed on the market?

Established use and scientific backing need to be proven while marketing these products. For the pharmaceutical industry it is imperative to spend time and money on developing a new drug if the application of the new drug, the compound from which it is made or the process used to make it can be innovative or at best patent protected. Since new drug development is fairly costly, the pharmaceutical industry remains interested in developing completely new active drug ingredients, as only these are market savvy or patentable.

The pharmaceutical industry is not generally that interested in medicinal plants as they do not contain a single definable and completely new active ingredient. Phytopharmaceutical producers are also well aware of the patent protection problem and solve it by developing special extracts with production processes that they can protect with a patent. They "invent" a special method to enrich or remove substances from an extract, so that the extract becomes something special. This invention can then be protected with a patent. These extracts are tested in clinical trials, approval is sought and, all being well, granted, as happens with standard drugs. Although this special manufacturing process enables manufacturers to protect their plantbased product, other manufacturers can easily find a way around it.

How do the regulatory requirements for herbal medicines, i.e. extracts, differ from those for synthetic drugs?

If we talk about the herbal formulations, every pharmacopoeial formulation is herbal but every herbal formulation is not pharmacopoeial. Along with herbal formulations approved under AYUSH considered safe & effective due to their earlier presence in the pharmacopoeial standards and are available to the end user without the prescription, which in itself defines its safety and efficacy due to which there are lot of waivers given by the AYUSH during the approval process.

But herbal formulations which are approved under Phytopharmaceutical category and also as said earlier are approved in a very stringent manner and they are available to the end user against a prescription only.

Additionally if we talk about the standardization of herbal medicines is often a very difficult task due to complexity of their diverse secondary metabolites, with therapeutic action which may vary with different geographical and tropical conditions & genetic differences between the populations & these complications remains same for approval of formulations under AYUSH & Phytopharmaceutical category.

Also, the harvesting process and period, coupled with incidents of adulterations due to the presence of microorganisms and pesticides have profound impact on achieving uniform standards of herbal medicines worldwide . Improvement in the quality of herbal medicines could be achieved by deliberate implementation of good agricultural practices (GAPs) at the point of cultivation of medicinal plants and good manufacturing practices (GMPs) during the process of manufacture and packaging of finished herbal products, as well as post-marketing quality assurance surveillance. Thus complications related to natural resourcing of ingredients of the formulations, identifying its potential of being therapeutically active are not present in Allopathic (synthetic drugs).

Quality continues to be a major theme across the nutritional and pharmaceutical ingredients marketplace. How do you see the future of herbal medicine research and development? What is the potential?

Quality of any medicine is of paramount importance. It all depends on the ingredients and the processing stage. In a chain, common GMP requirements are implemented which are as follows:
  • Cultivation/collection/drying/minimal processing/storage and transport of the raw herb.
  • Grinding/extraction/fractional steps/other operations like spray drying/tray drying/packing and storage of the botanical process.
  • The formulation based on compatibility with excipients/dosage form choose from product formulation/different steps involved in the manufacture.
Moreover, it is expected that this section will be developed more in the coming future and the applicants are advised to adopt a process that will prohibit contamination, destruction and helps in protecting the quality and veracity of the final product.

The use of cutting-edge analytical techniques and well-thought-out research methodologies, the prospects of advancing the frontiers of knowledge in herbal medicine is now at an alltime high. Additionally, following the current sustained improvements in quality control and regulatory measures in many countries of the world, it is envisaged that in the near future, herbal medicine will be integrated into conventional medical systems.

Or else I also be said as herbal formulations will soon be replacing the synthetic formulations from the markets of Asian countries and countries like Germany also by the end of the century.

Is patient education still an important topic when it comes to Phytopharmaceuticals?

Yes, patient education will play an important role to differentiate the importance of phytopharmaceuticals with other undocumented herbal formulation present in the market.

The available herbal remedies market can be classified into five strategic areas:
1. Phyto-Pharmaceuticals: the plant-based drugs containing isolated pure active compounds used to treat diseases
2. Medicinal Botanicals/Dietary Supplements: the whole plant or plant-part extracts used for maintenance of health by affecting a body structure and its function
3. Nutraceuticals: the food containing supplements from natural (botanical) sources, that deliver a specific health benefit, including prevention and treatment of disease
4. Cosmeceuticals: the cosmetic products which contain biologically active ingredients having an effect on the user end
5. Herbal raw material: they are prepared using pure and herbal extracts.