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Nutraceuticals: Still An Oasis Amidst Well-Regulated Pharmaceuticals

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On November 24, 2016, the food-safety watchdog of India announced that health supplements or Nutraceuticals cannot be sold as ‘medicines’ anymore. This new regulatory standard has been set for the manufacturers of Nutraceuticals and food supplements, and is aimed at controlling mislabeling of such brands. The fine prints of the notification are yet to be assessed.

On the face of it, this new announcement seems to be a good step, and would largely address a long-standing issue on the such products. Prevailing undesirable practices of labeling some pharma brands as food supplements or Nutraceuticals, with some tweaking in the formulations, mainly to avoid the risk of price control, is also expected to be taken care of by the food-safety authority of India, while granting marketing approval.

Nevertheless, it is often construed that off-label therapeutic claims, while promoting these products to the doctors, help achieving brand positioning objective as medicines, though indirectly. Appropriate authorities in India should probably resolve this issue, expeditiously.

In this article, I shall focus on the rationale behind different concerns over the general quality standards, claimed efficacy and safety profile of Nutraceuticals and food supplements, in general, and how the regulatory authorities are responding to all these, slowly, albeit in piecemeal, but surely.

The ‘gray space’ is the issue:

The close association between nutrition and health has assumed a historical relevance. Growing pieces of evidence, even today, suggests that nutritional intervention with natural substances could play an important role, especially in preventive health care. The World Health Organization (WHO) has also highlighted that mortality rate due to nutrition related factors in the developing countries, like India, is nearly 40 percent.

However, as one of the global consulting firm of repute has aptly pointed out, “At one end of this natural nutrition spectrum, are functional foods and beverages as well as dietary supplements, aimed primarily at maintaining health. On the other, more medical end of the spectrum, are products aimed at people with special nutritional needs. In the middle, is an emerging gray area of products that have a physiological effect to reduce known risk factors, such as high cholesterol, or appear to slow or prevent the progression of common diseases such as diabetes, dementia or age related muscle loss.”

This gray space between Pharmaceutical and Nutraceuticals, therefore, holds a significant business relevance, from various perspectives.

An Oasis amidst highly-regulated pharmaceuticals:

Mostly because of this gray space, several pharma companies and analysts seem to perceive the Nutraceutical segment virtually an oasis, lacking any transparent regulatory guidelines, amidst well-regulated pharma business. This perception is likely to continue, at least, for some more time.

Such pattern can be witnessed both within the local and global pharma companies, with some differences in approach, that I shall deliberate later in this article.

However, regulators in many countries, including India, have started expressing concerns on such unfettered manufacturing, marketing and other claims of Nutraceuticals. Many of them even ask, do all these Nutraceuticals deliver high product quality, claimed effectiveness and safety profile to their consumers, especially when, these are promoted by several pharma companies, though mostly off-label, to generate physicians’ prescriptions for various disease treatments?

Not just domestic pharma companies:

This concern is not restricted to the domestic companies in India.

Global pharma players, who generally believe in scientific evidence based medicines, have been reflecting an iffiness towards Nutraceuticals. For example, whereas both Pfizer and Novartis reportedly hived off their nutrition businesses, later Pfizer invested to acquire Danish vitamins company Ferrosan and the U.S. dietary supplements maker Alacer. Similarly, both Sanofi and GlaxoSmithKline also reportedly invested in mineral supplements businesses that could probably pave the way of the company’s entry into medical foods.

However, it is worth underscoring that generally the consumer arms of global pharma companies focus on OTC, and Nutraceuticals do not become an integral part of the pharma business, as is common in India.

Interestingly, not very long ago, Indian pharma industry witnessed a global pharma major virtually replicating the local marketing model involving Nutraceuticals. It also became an international news. On August 24, 2011, ‘Wall Street Journal (WSJ)’ reported that ‘Aventis Pharma Ltd. (now Sanofi India) agreed to buy the branded nutrition pharmaceuticals business of privately held Universal Medicare Pvt. Ltd for an undisclosed amount, as its French parent Sanofi looks to expand in the fast-growing Indian market.’

Universal Medicare, which posted about US$ 24.1 million revenue in the year ended March 31, 2011, will manufacture these branded Nutraceutical products and Aventis will source them from Universal Medicare on mutually agreed terms. Around 750 of the Universal Medicare’s employees also moved to the French Company along with its around 40 Nutraceutical brands, the report said.

If all these acquired brands, do not fall under the new FSSAI guidelines related to the required composition of food supplements and Nutraceuticals in India, it would be worth watching what follows and how.

Nutraceuticals are also promoted to doctors:

Let me reemphasize, India seems to be slightly different in the way most of the pharma companies promote Nutraceuticals in the country. Here, one can find very few standalone ‘Over the Counter (OTC)’ pharma or Nutraceutical product company. For this reason, Nutraceutical brands owned by the pharma companies, usually become an integral part of their prescription product-portfolio. Mostly, through off-label promotion Nutraceuticals are often marketed for the treatment or prevention of many serious diseases, and promoted to the doctors just as any other generic pharma brand.

Need to generate more scientific data based evidences:

A 2014 study of the well-known global consulting firms A.T. Kearney titled, “Nutraceuticals: The Front Line of the Battle for Consumer Health”, also recommended that ‘a solid regulatory framework is crucial for medical credibility, as it ensures high-quality products that can be relied on to do what they say they do.’

This is mainly because, Nutraceuticals are not generally regarded by the scientific community as evidence based medicinal products, going through the rigors of stringent clinical trials, including pharmacokinetics and pharmacodynamics studies, and is largely based on anecdotal evidence. Besides inadequacy in well-documented efficacy studies, even in the areas of overall safety in different age groups, other side-effects, drug interactions and contraindications, there aren’t adequate scientific evidence based data available to Nutraceutical manufacturers, marketers, prescribers and consumers.

There does not seem to be any structured Pharmacovigilance study is in place, either, to record adverse events. In this scenario, even the ardent consumers may neither realize, nor accept that Nutraceuticals can cause any serious adverse effects, whatsoever.

From this angle, the research study titled, “Emergency Department Visits for Adverse Events Related to Dietary Supplements”, published in the  New England Journal of Medicine (NEJM) on October 15, 2015, becomes very relevant. The paper concluded as follows:

“More than 23,000 emergency department visits annually in the United States from 2004 through 2013 were for adverse events associated with dietary supplements. Such visits commonly involved cardiovascular adverse effects from weight-loss or energy herbal products among young adults, unsupervised ingestion of micronutrients by children, and swallowing problems associated with micronutrients among older adults. These findings can help target interventions to reduce the risk of adverse events associated with the use of dietary supplements.”

Fast growing Nutraceutical industry continues to remain largely unregulated. It persists, even after several previous studies had revealed dangerous levels of harmful ingredients, including amphetamine, in some Nutraceuticals.

Indian regulatory scenario:

In India, the ‘Food Safety and Standards Authority of India (FSSAI)’, established under the Food Safety and Standard Act of 2006, is the designated Government body responsible for the regulation and approval of Nutraceuticals in the country.

In July 2015, FSSAI proposed draft regulations for Nutraceuticals, Functional Foods, Novel Foods and Health Supplements for comments from all stakeholders within the stipulated time limit. This draft regulation defines Nutraceuticals as follows:

“Nutraceuticals means a naturally occurring chemical compound having a physiological benefit or provide protection against chronic disease, isolated and purified from food or non-food source and may be prepared and marketed in the food-format of granules, powder, tablet, capsule, liquid or gel and may be packed in sachet, ampoule, bottle, etc. and to be taken as measured unit quantities.”

In this draft FSSAI also proposed that therapeutic claims of Nutraceuticals and all such foods are required to be based on sound medical and nutritional evidence, backed by scientific as well as clinical evidence.

In 2011, FSSAI constituted a product approval committee, whose members were supposed to use similar parameters as drugs, to assess Nutraceuticals for this purpose. However, FSSAI had to jettison this idea, in compliance with the order dated August 19, 2015 of the Supreme Court questioning the procedure followed for approvals by the food regulator.

In April 2016, FSSAI restricted enforcement activity against Nutraceuticals and health supplement companies to only testing of products till new standards are notified.

The latest regulatory developments:

There are, at least, the following two recent developments reflect that the regulatory authorities, though trying, but are still grappling with the overall product quality, efficacy and safety concerns for Nutraceuticals:

  • Responding to the growing demand for regulatory intervention in this important matter, on November 30, 2015, by a gazette notification, the Government of India included phytopharmaceutical drugs under a separate definition in the Drugs & Cosmetics (Eighth Amendment) Rules, 2015, effective that date.
  • Again, on November 24, 2016, FSSAI reportedly announced that health supplements or Nutraceuticals cannot be sold as ‘medicines’ anymore. This new regulatory standard set for the manufacturers of Nutraceuticals and food supplements is aimed at controlling mislabeling of such brands. On its enforcement, every package of health supplement should carry the words ‘health supplement’ as well as an advisory warning ‘not for medicinal use’ prominently printed on it.

It further added: “The quantity of nutrients added to the articles of food shall not exceed the recommended daily allowance as specified by the Indian Council of Medical Research and in case such standards are not specified, the standards laid down by the international food standards body namely the Codex Alimentarius Commission shall apply.”

However, these regulations will be enforced from January 2018.

Curiously, in September 2016, National Institutes of Health in United States announced plans to put some more scientific eyes on the industry, the NIH reportedly announced plans to spend US$ 35 million to study natural products, ranging from hops to red wine’s resveratrol to grape seed extract. The new grants, reportedly, are expected to fathom the basic science behind many claims that Nutraceuticals can improve health.

The market:

The August 2015 report titled, ‘Indian Nutraceuticals, Herbals, and Functional Foods Industry: Emerging on Global Map,’ jointly conducted by The Associated Chambers of Commerce and Industry of India (ASSOCHAM) and the consulting firm RNCOS, estimates that the global Nutraceuticals market is expected to cross US$ 262.9 billion by 2020 from the current level of US$ 182.6 billion growing at Compound Annual Growth Rate (CAGR) of about 8 percent.

Driven by the rising level of awareness of health, fitness and changing lifestyle pattern, increasing co-prescription with regular drugs, and focus on preventive health care, India’s Nutraceuticals market is likely to cross US$ 6.1 billion by 2020 from the current level of US$ 2.8 billion growing at CAGR of about 17 percent, the report states.

The United States (US) has the largest market for the Nutraceuticals, followed by Asia-Pacific and European Union. Functional food is the fastest growing segment in the US Nutraceutical market, followed by Germany, France, UK and Italy in Europe.

Conclusion:

Today, both manufacturing and marketing of Nutraceuticals keep charting in a very relaxed regulatory space, in India. There are no robust and transparent guidelines, still in place, for product standardization and scientifically evaluate the safety and efficacy of all these products on an ongoing basis. Neither is there any stringent requirement for conformance to the well-crafted cGMP standards.

The reported discussions within the Union Ministry of Ayush for setting up a structured regulatory framework, within the CDSCO, for all Ayush drugs and to allow marketing of any new Ayurvedic medicine only after successful completion of clinical trials to ensure its safety and efficacy, are indeed encouraging. This may be followed for all those Nutraceuticals, which want to be promoted as medicines, claiming direct therapeutic benefits.

Be that as it may, November 24, 2016 announcement of FSSAI, that health supplements or Nutraceuticals cannot be sold as ‘medicines’ anymore to control mislabeling of such brands, is a step in the right direction.

Another major issue of many pharma brands being put under Nutraceuticals with some tweaking in formulations and labelled as food supplements, would also probably be largely addressed, as FSSAI would continue to be the sole authority for marketing approval of Nutraceuticals.

However, it is still not very clear to me, as I am writing this article, what happens to those Nutraceutical brands, which are already in the market, with compositions not conforming to the new FSSAI norms. Fairness demands reformulation and relabeling of all those existing Nutraceuticals, strictly in conformance to the new guidelines, and obtain fresh approval from FSSAI. This will help create a level playing field for all Nutraceutical players in India.

While there is a pressing need to enforce a holistic regulatory discipline for the Nutraceuticals to protect consumers’ health interest, the commercial interest of such product manufacturers shouldn’t be ignored, either. This is primarily because, there exists enough evidence that proper nutritional intervention with the right kind of natural substances in the right dosage form, could play an important role, especially in the preventive health care.

As the comprehensive regulatory guidelines are put in place, Nutraceuticals not being essential medicines, should always be kept outside price control, in any guise or form. In that process, the general pharma perception of Nutraceutical business, as an ‘Oasis’ amidst well-regulated and price-controlled pharmaceuticals, would possibly remain that way, giving a much-needed and well-deserved boost to this business.

By: Tapan J. Ray   

Disclaimer: The views/opinions expressed in this article are entirely my own, written in my individual and personal capacity. I do not represent any other person or organization for this opinion.

Nutraceuticals: Make The Fragile Regulatory Space Robust, Soon

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In the space between drugs and nutrition, there is an intriguing ‘gray area’ with significant business relevance, especially in India.

In a related publication, A.T. Kearney – a leading global management consulting firm has elaborated it as below:

“At one end of this natural nutrition spectrum, are functional foods and beverages as well as dietary supplements, aimed primarily at maintaining health. On the other – more medical end of the spectrum, are products aimed at people with special nutritional needs. In the middle, is an emerging gray area of products that have a physiological effect to reduce known risk factors, such as high cholesterol, or appear to slow or prevent the progression of common diseases such as diabetes, dementia or age related muscle loss.”

Falling in the middle of the spectrum, a large number of Nutraceuticals clearly blur the line between food and drugs, in many cases. In India, there is no clearly defined legal and regulatory status for such Nutraceuticals, just yet.

Why a robust regulation required for Nutraceuticals? 

The scholarly article of S.H. Zeisel (Professor of Nutrition, University of North Carolina at Chapel Hill Nutrition) titled, “Regulation of Nutraceuticals,” Science 5435, 1853–1855 (1999) highlighted that in many cases when the dosages of food supplements exceed those of a normal diet, there could well be a drug-like bioactivity of a nutrient.

An example of the nutrient tryptophan may suffice to illustrate this point briefly. At higher dosage tryptophan can exhibit drug-like activity, as it is the precursor of serotonin, which is extensively used to treat insomnia. Many of such points are yet to draw the regulators’ attention in India as much as it should, as yet.

Marketing drugs as ‘food supplements’?

Marketing drugs as food supplements to evade Drug Price Control Order (DPCO) by some pharma players, of all sizes and scale of operation, is not an uncommon practice in India. The National Pharmaceutical Pricing Authority (NPPA), reportedly, pointed it out sometime around 2009.

Not just for pricing reason, but more importantly for consumers’ health and safety, the Central Drugs Standard Control Organization (CDSCO) should address this issue now with a greater sense of urgency, as the market for Nutraceuticals and health supplements is reportedly growing at a brisk pace today. According to a Frost & Sullivan report, the total Indian Nutraceuticals market in 2015 was expected around US $ 5 billion. 

In the absence of any clear and robust regulatory guidelines, most Nutraceutical products, with a spectrum of therapeutic claims, are virtually self-categorized as food supplements, which are not covered under the Drugs and Cosmetics Acts in India.

Currently in the country, Nutraceuticals and functional foods are covered under the definition of ‘food’ as per Section 22 of Food Safety & Standards Act (FSSA), 2006. These food products have been categorized as Non-Standardized/Special Food Products. Accordingly, Food Safety and Standards Authority (FSSAI) of India have described Nutraceuticals as:

“Naturally occurring chemical compound having a physiological benefit or provide protection against chronic disease, isolated and purified from food or non-food source.”

Though categorized as nutritional supplement, the product packs of such Nutraceuticals usually do not carry any “FSSAI’ logo, which signifies conformance to the food safety standards of India, for the benefit of consumers.

Recommendations are many, but no comprehensive action yet:  

To give an example, many Nutraceuticals contain vitamins in varying quantity. However, most of these products seem to carefully avoid Schedule V guidelines for vitamin content to avoid being categorized as drugs, and thereby coming under strict regulatory requirements. Self-categorizing these products as ‘food supplement’, helps bypassing this issue, as on date.

Such ongoing practices related to Nutraceuticals need to be viewed keeping in perspective, some of the recent key recommendations made by the Drugs Technical Advisory Board (DTAB) of the CDSCO, on Schedule V related formulations.

The minutes of the 70th. meeting of the Drugs Technical Advisory Board (DTAB) held on August 18, 2015, recorded the acceptance of the report of its sub-committee on vitamins, which recommended, among others, some of the following guidelines:

  • Ingredients which are covered under the range as prescribed under schedule “V” of the Drugs and Cosmetics Rules for Tablets, capsules, granules are 18 classified as a drug, while those powders like Farex, Oats and Cereal fortified vitamins are exempted from the provisions of chapter IV under schedule K of Drugs and Cosmetics Rules.
  • Ingredients which fall below the range as prescribed under schedule “V” shall be classified as food. However, if there is a claim for treatment, mitigation or prevention of any diseases or disorder, then it will be classified as a drug. 
  • Ingredients which are within Recommended Daily Allowance (RDA) levels, but fall under the range as prescribed under schedule V Drugs and Cosmetics Rules shall be classified under drug as it is already mentioned in the rules. 
  • Products containing ingredients which are neither covered under Schedule V nor fall within RDA, these can be classified as unprovable products under Drugs and Cosmetics Rules, unless otherwise specifically permitted by the Licensing Authorities of drugs based on major purpose of the item (like food/drug).
  • Whenever there are additional ingredients than those given in schedule V, including some of herbal ingredients, a separate and conscious view has to be taken about the safety and efficacy of the drug
  • Any product containing herbal ingredients shall be dealt with by the food or drug authority based on the above principles. 

The same subcommittee, on June 12, 2015, after discussing each of some specified products, with a claim of falling in non-drug category, as per directions of the Hon’ble High Court of Patna, recommended categorization of some of the well-known brands brands, such as, Revital (Ranbaxy) and A to Z capsules (Alkem) as drugs. The sub-committee report was then uploaded in the CDSCO website for stakeholders’ comment.

Could there be ‘irrational FDC ban’ like an issue with Nutraceuticals?

The answer to this question is anybody’s guess at this point of time. However, such a possibility can be just wished away either.

This lurking fear stems from the recent notification of FSSAI dated March 30, 2016, which states as follows:

“It has been decided that till the standards of Nutraceuticals, food supplements and health supplements are finally notified, the enforcement activities against such food business operators may be restricted to testing of these products with respect to requirements given in the draft notification on such products of September 9, 2015″.

However, it clarifies that the companies will get an exemption, if such products were available in the market before the Food Safety and Standards Act came into effect in 2011, or if product approval was pending on August 19, 2015.

The key objective of the above September 9, 2015, FSSAI draft notification was to ensure that Nutraceuticals, health and food supplements and other such products are not sold as medicines with therapeutic claims. Thus, asking the industry players to send their suggestions and objections to the proposal, this draft notification indicates, among others, that all such products should: 

  • Adhere to the proposed permissible limits of various minerals, vitamins, plant or botanical-based ingredients, among others.
  • Adhere to the proposed list of food additives used in all these categories of products, besides labelling norms, every package must carry the words “Food” or “Health Supplement” and prominently display “Not for Medicinal Use” on the label. 
  • Give a disclaimer on the package that the food or health supplement should not be used as a substitute for a varied diet.
  • Clearly indicate on the label that “this product is not intended to diagnose, treat, cure or prevent any disease”, besides information on recommended dosages, among others.

As this notification is expected to cover all products, which are marketed as food supplements, many Nutraceuticals manufacturers, reportedly, fear that it could effectively mean a ban on virtually all those brands, self-categorized as food or nutritional supplement, and launched post 2011.

If it happens, the saga of ban of a large number of irrational Fixed-Dose Combinations (FDCs) of drugs, that includes some top-selling pharma brands and is now sub judice, could get extended to the Nutraceuticals sector too. 

Nonetheless, the bottom-line is that a robust mechanism to effectively regulate and monitor Nutraceuticals in India, is yet to see the light of the day. 

Crazy marketing of Nutraceuticals: 

Despite regulatory and marketing restrictions to the therapeutic claims for this category of drugs, Nutraceuticals are mostly promoted to the doctors, just as any other ethical pharma products in India.

Consequently, these are widely prescribed by the medical profession, not just as nutritional supplements, but also for the treatment of disease conditions, ranging from obesity to arthritis, osteoporosis, cardiovascular conditions, diabetes, anti-lipid, gastrointestinal conditions, dementia, age-related muscle loss, pain management and even for fertility. All these are generally based on off-label therapeutic claims of the respective manufacturers.

Being advertised in the mass media too:

To illustrate this point, I would give an example of a well known brand in India. As I see from the Government records, i.e. from the minutes of the 68th meeting of the DTAB sub-committee held on June 12, 2015 that it had recommended Revital’s (Ranbaxy) categorization under drug.

As we all know that, as per drugs and Cosmetics Act of India, drugs cannot be advertised in the mass media, except Schedule K drugs, such as Aspirin and paracetamol. In that sense, I find it difficult to fathom, how is Revital then, which highlights a naturally occurring substance fortified with vitamins and minerals, advertised even on the Television, along with a top celebrity endorsement?

A recent notification on phytochemicals:

As I mentioned in my article in this Blog on December 21, 2015, titled “Nutraceuticals: A Major regulatory Step That Was Long Overdue”, partly responding to the growing demand for regulatory intervention in this important matter, on November 30, 2015, by a gazette notification, the Government of India included phytopharmaceutical drugs under a separate definition in the Drugs & Cosmetics (Eighth Amendment) Rules, 2015, effective that date.

This regulatory action followed the rapidly growing use of these drugs in India, which includes purified and standardized fraction with defined minimum four bio-active or phytochemical compounds.

On the ground, this significant regulatory measure would require the pharma players to submit the specified data on phytopharmaceutical drugs, along with necessary applications for conduct clinical trial or import or manufacture of these products in the country. 

However, this is no more than half-measure in this direction. Hopefully, this will be followed by final action on the DTAB recommendations on vitamins, and final notification of FSSAI on standards of Nutraceuticals, food and health supplements. A well-integrated action of the CDSCO and FSSAI, would possibly help to contain the unregulated proliferation of various types of Nutraceutical products coming into the Indian market, prescribed by the doctors and consumed by the people, sans any scientific evidence based efficacy, safety and quality standards.

Manufacturers’ business interest also can’t just be ignored:

While there is a pressing need to enforce regulatory discipline for claimed efficacy, safety and high quality standards for the Nutraceuticals to protect consumers’ health interest, commercial interest of such drug manufacturers can’t also just be ignored. If that happens, it will be unfair.

Thus, one of the ways to encourage the manufacturers to expand this market, I reckon, could well be categorizing the Nutraceuticals offering health benefits, under a separate category altogether, which will be kept out of any form of drug price control.

Conclusion:

The manufacturers of Nutraceuticals still keep charting in a very relaxed regulatory space. Currently, there is no robust and transparent process in place to standardize and scientifically evaluate safety and efficacy of these products on an ongoing basis. This scenario should not be allowed to continue, any longer.

Appropriate control of standardized Nutraceutical manufacturing, regular monitoring of the same and scientific evidence-based marketing approval process of all such products, therefore, require to be well-well regulated. The requirement for stringent conformance to the set cGMP standards would ensure desired safety, efficacy and high quality of nutraceutical products for the consumers.

The recent decisions of the Union ministry of Ayush for setting up a structured regulatory framework, within the CDSCO, for all Ayush drugs and to allow marketing of any new Ayurvedic medicine only after successful completion of clinical trials to ensure its safety and efficacy, are indeed encouraging.

Just as Ayurvedic products, all Nutraceuticals, not being essential medicines, should always be kept outside price control in any form. It should happen in tandem with the Government’s taking a bold step to make the prevailing fragile regulatory space for the Nutraceuticals a robust one, creating a win-win situation for all. 

By: Tapan J. Ray

Disclaimer: The views/opinions expressed in this article are entirely my own, written in my individual and personal capacity. I do not represent any other person or organization for this opinion.

Nutraceuticals: A Major Regulatory Step That Was Long Overdue

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Currently in India the nutraceutical products segment, with surrogate or off-label therapeutic claims, is growing at a reasonable pace.

Many such products are now being directly promoted to the medical profession, just like any other modern medicines, with therapeutic claims not being supported by robust clinical data that can pass through scientific or regulatory scrutiny.

For such use of nutraceutical products, I raised the following two questions in my article on this Blog titled, “Nutraceuticals with Therapeutic Claims: A Vulnerable Growing Bubble Protected by Faith and Hope of Patients” on August 27, 2012: 

  • What happens when the nutraceutical products fail to live up to the tall claims made by the respective manufacturers on their efficacy and safety profile?
  • Are these substances safe in those conditions, even when not enough scientific data has been generated on their long term toxicity profile?

Importance of robust clinical data for any product with therapeutic claims:

For similar claim of therapeutic efficacy in the treatment of a disease condition, any drug would require establishing its pharmacokinetics and pharmacodynamics with pre-clinical and clinical studies, as stipulated by the drug regulators. Some experts believe that these studies are very important for nutraceutical products as well, especially when therapeutic claims are made on them, directly or indirectly. This also because, these substances are involved in a series of reactions within the body. 

Similarly, to establish any long term toxicity problem with such products, generation of credible clinical data, including those with animal reaction to the products, both short and long term, using test doses several times higher than the recommended ones, is critical. These are not usually followed for nutraceutical products in India, even when therapeutic claims are being made.

Some experts in this field, therefore, quite often say, “A lack of reported toxicity problems with any nutraceutical should not be interpreted as evidence of safety.” 

The current status:

Currently in India, nutraceuticals, herbals and functional foods are covered under the definition of ‘food’ as per Section 22 of Food Safety & Standards Act, 2006. These food products have been categorized as Non-Standardized/special food products. Neither was there any properly framed guidelines related to manufacturing, storage, packaging & labeling, distribution, sales, claims and imports, nor any legal fear of counterfeiting.

A recent reiteration of the need of regulatory guidelines for nutraceuticals:

In a study on ‘Indian Nutraceuticals, Herbals, and Functional Foods Industry: Emerging on Global Map,’ jointly conducted by The Associated Chambers of Commerce and Industry of India (ASSOCHAM) and RNCOS and released by ASSOCHAM on August 17, 2015 the above key apprehensions on the lack of any kind of regulatory guidelines for the approval and monitoring of products falling under this segment, were reiterated.

The market:

According to the above study, the global nutraceuticals market is expected to cross US$ 262.9 billion by 2020 from the current level of US$ 182.6 billion growing at a compound annual growth rate (CAGR) of about 8 percent.

United States (US) has the largest market for the nutraceuticals, followed by Asia-Pacific and European Union. Functional food is the fastest growing segment in the US nutraceuticals market. Germany, France, UK and Italy are the major markets in the European Union for nutraceuticals. Japan (14 percent) is the major consumer of nutraceuticals in Asia-Pacific, followed by China (10 percent).

The Indian nutraceuticals market is at a nascent stage now, but fast emerging. India accounts for around 1.5 percent of the global market. However, the above study forecasts that due to rising awareness of health and fitness and changing lifestyle, India’s Nutraceuticals market is likely to cross US$ 6.1 billion by 2020 from the current level of US$ 2.8 billion, growing at a compound annual growth rate (CAGR) of about 17 percent. 

Phytochemicals in nutraceuticals:

Phytochemicals have been broadly defined as chemical compounds occurring naturally in plants. A large number of phytochemicals, either alone and/or in combination, are currently being used as nutraceuticals with significant impact on the health care system, claiming a number of medical health benefits, including prevention, treatment and even cure of many types of diseases.

The most recent regulatory intervention:

Responding to the growing demand for regulatory intervention in this important matter, on November 30, 2015, by a gazette notification, the Government of India included phytopharmaceutical drugs under a separate definition in the Drugs & Cosmetics (Eighth Amendment) Rules, 2015, effective that date.

This regulatory action also followed the rapidly growing use of these drugs in India, which includes purified and standardized fraction with defined minimum four bio-active or phytochemical compounds. 

On the ground, this significant regulatory measure would necessarily require the pharma players to submit the specified data on the phytopharmaceutical drug, along with the application to conduct clinical trial or import or manufacture in the country.

The salient features of the notification:

I am summarizing below, only the salient features of the detail notification for obtaining regulatory approval of these drugs in India:

A. Data to be submitted by the applicant:

A brief description or summary of the phytopharmaceutical drug giving the botanical name of the plant: 

- Formulation and route of administration, dosages

- Therapeutic class for which it is indicated

- The claims to be made for the phytopharmaceutical product.

- Published literature including information on plant or product or phytopharmaceutical drug, as a traditional medicine or as an ethno medicine and provide reference to books and other documents, regarding composition, process prescribed, dose or method of usage, proportion of the active ingredients in such traditional preparations per dose or per day’s consumption and uses.

- Information on any contraindications, side effects mentioned in traditional medicine or ethno medicine literature or reports on current usage of the formulation.

- Published scientific reports in respect of safety and pharmacological studies relevant for the phytopharmaceutical drug intended to be marketed.

- Information on any contraindications, side effects mentioned or reported in any of the studies, information on side effects and adverse reactions reported during current usage of the phytopharmaceutical in the last three years, wherever applicable.

- Present usage of the phytopharmaceutical drug ,  –  to establish history of usages, provide details of the product, manufacturer, quantum sold, extent of exposure on human population and number of years for which the product is being sold. 

B. Human or clinical pharmacology information

C. Identification, authentication and source of plant used for extraction and fractionation

D. Process for extraction and subsequent fractionation and purification

E. Formulation of phytopharmaceutical drug applied for

F. Manufacturing process of formulation

G. Stability data

H. Safety and pharmacological information

I. Human studies

J. Confirmatory clinical trials

K. Regulatory status in other countries

L. Marketing information, including text of package inserts, labels and cartons

M. Post marketing surveillance (PMS)

N. Any other relevant information that will help in scientific evaluation of the application

Conclusion:

Prior to the above gazette notification, companies marketing nutraceutical products in general and phytochemical products, in particular, used to operate under a very relaxed regulatory framework.

Such products are currently promoted with inadequate disclosure of science based information, particularly with the surrogate therapeutic claims, which are based merely on anecdotal evidence and forms a part of intensive off-label sales and marketing efforts on the part of respective marketing players. It continues to happen, despite the fact that off-label therapeutic claims for any product are illegal in India, just like in many other countries.

Appropriate measures now being taken by the Government on phytochemical drugs, are expected to further plug the regulatory loopholes for off-label therapeutic claims without any robust scientific evidence. This particular regulation would also, hopefully, help curbing marketing malpractices to boost sales turnover of such products.

Considering all this, it appears that this is a major regulatory step taken by the Indian Government that was, in fact, very long overdue. Implemented properly, this would ensure predictable health outcomes and improved safety standards for most of the nutraceutical products, solely keeping patients’ health interest in mind.

By: Tapan J. Ray

Disclaimer: The views/opinions expressed in this article are entirely my own, written in my individual and personal capacity. I do not represent any other person or organization for this opinion.