Tag Archives: 2006

Nutraceuticals: A Major Regulatory Step That Was Long Overdue

Posted on by
Reply

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.

Global New Product Launches: Recent Success Trend Unflattering?

Posted on by
Reply

New products are the lifeblood for any company, including the pharmaceutical players. Business performance and sustainable growth of the pharmaceutical industry, as a whole depend on quality of R&D output in terms of ‘New Molecules’, followed by successful development and launch of those new products by the global pharmaceutical innovators.

Post-patent expiry, robust development and ‘just in time’ launch of cheaper generic versions of those innovative products, in a mega scale, usually drive the growth of the generic pharmaceutical industry, globally.

It is worth noting that for the last several years, ‘Patent Cliff’ coupled with progressively drying up R&D pipelines and mostly unflattering new product launches, are taking heavy tolls on the business performance of the global pharmaceutical majors.

The changing dynamics need to be considered:

Echoing this development, a March 2014 report of McKinsey & Company states: “About two-thirds of drug launches don’t meet sales expectations. Improving that record requires pharmaceutical companies to recognize the world has changed and adjust their marketing accordingly.”

To analyze the situation now in perspective, let us start tracking the launches from 2006 and 2007.

10 Big Pharma Sales in 2012 from NMEs approved since 2007 – A comparison

According to a June 2013 report of the ‘FirstWord Pharma’, in 2012 the combined sales of 10 top Big Pharma constituents, as named in the tables below, from the New Molecular Entities (NMEs) approved by the US-FDA since 2007, were US$ 14.8 billion i.e. 4.9 percent of the total revenue of these 10 companies in that year from the patented drugs.

Individual performance of these 10 companies are as follows:

No. Company Sales US$ Million Sales from NMEs US$ Million As % of 2012 Sales
1. Novartis 32153 3445 10.7
2. J&J 25351 2593 10.3
3. BMS 17621 1495 8.5
4. GSK 28518 1282 4.5
5. Merck 35945 1515 4.2
6. Sanofi 30879 1265 4.1
7. Roche 37578 1238 3.3
8. Eli Lilly 20566 457 2.2
9. Pfizer 47496 1040 2.2
10 AstraZeneca 27925 449 1.6

(Source: FirstWord, June 2013)

The success rate: With 2007 as the base year for NMEs

This table shows that Novartis and Johnson & Johnson were the two most successful companies with the launch of such NMEs in 2012, as they generated 10.7 percent and 10.3 percent, respectively, of their total patented drugs sales from these NMEs, as against an average of 4.9 percent, as mentioned above, during that year.

If we now try to analyze the new product launch success rates of the 10 Big Pharma constituents, based on the contribution of these new products (launched since 2007) to their respective total sales in 2012, the following picture emerges:

  • Good:  More than 10 percent - 2 Companies (20 percent)
  • Average: Between 5 and 10 percent - 1 Company (10 percent)
  • Poor: Less than 5 percent - 7 Companies (70 percent)

The success rate: With 2006 as the base year for NMEs

It is interesting to note from this report that by extending the ‘review period’ to NMEs approved by the US-FDA between 2006 and 2012 (i.e. one additional year), revenues generated by these new drugs in 2012 double to US$ 29 billion – or approximately 10 percent (instead of earlier 4.9 percent) of the total combined branded drug sales of the same 10 Big Pharma constituents in the same year, as follows:

No. Company Sales US$ Million Sales from NMEs US$ Million As % of 2012 Sales
1. Merck 35945 7518 20.9
2. Novartis 32153 5843 18.2
3. J&J 25351 3939 15.5
4. BMS 17621 2514 14.3
5. Roche 37578 2818 7.5
6. Pfizer 47496 2946 6.2
7. GSK 28518 1282 4.5
8. Sanofi 30879 1265 4.1
9. Eli Lilly 20566 457 2.2
10 AstraZeneca 27925 449 1.6

(Source: FirstWord, June 2013)

No significant overall qualitative change:

Here also, though some numbers related to the new product launch success rates of the same 10 Big Pharma constituents, based on the contribution of the NMEs launched since 2006 to their respective total sales in 2012 do change, poor to average performance with the new products still remains quite high, as follows:

  • Good: More than 10 percent - 4 Companies (40 percent)
  • Average: Between 5 and 10 percent - 2 Company (20 percent)
  • Poor: Less than 5 percent - 4 Companies (40 percent)

However, at a company level, the broad success trend with new products does not change very significantly. Just two new products approved by the US-FDA in 2006 were off to flying starts. These were:

  • Januvia of Merck: Generated sales of US$ 5.7 billion in 2012
  • Lucentis of Novartis and Roche: Generated combined sales of US$ 4 billion in 2012

Is it practically ‘The End’ of blockbuster drugs era?

While considering the larger picture on the subject, does it mean that Januvia and Lucentis would mark the end of the golden era of global blockbuster drugs…at least for now?

This picture may get clearer with the following table, prompting possibly an affirmative answer:

Best selling NMEs launched since 2006:

No. Product Company Approval Year 2012 Sales in US$ Million
1. Januvia Merck 2006 5745
2. Lucentis Novartis 2006 2398
3. Lucentis Roche 2006 1580
4. Isentress Merck 2007 1515
5. Invega J&J 2006 1346
6. Sutent Pfizer 2006 1236
7. Gilenya Novartis 2010 1195
8. Stelara J&J 2009 1025
9. Sprycel BMS 2006 1019
10 Tasigna Novartis 2007  998

(Source: FirstWord, June 2013)

Successfully launched most recent product is also on a shaky ground:

The new game-changing hepatitis C drug of Gilead Sciences – Sovaldi, has generated a turnover of around US$ 140 million in less than a month’s time from its market launch. Analysts expect an annual turnover of around US$7 billion from this brand.

However, sustaining the current sales momentum for Sovaldi in the years ahead could indeed be challenging for Gilead, as Bristol-Myers Squibb is preparing to obtain FDA approval for its own hepatitis C treatment daclatasvir, which has already been cleared in Europe. In addition, AbbVie is also progressing fast with its novel three-drug fixed dose combination in the same therapy area.

Moreover, Sovaldi’s unusually high price has reportedly created a furore in the western market. It costs US$ 1,000 a pill, raising huge concern among insurers and state funded healthcare providers in the United States. The report states that three Democratic members of the House Energy and Commerce Committee have already demanded that Gilead Sciences must justify the price of Sovaldi.

Categorization of new drugs:

Analyzing the current situation the above McKinsey report categorizes the types of new products that are now being launched, as follows:

  • Roughly one in four launches involves drugs that are strongly differentiated from competing products.
  • More than half of upcoming launches are of moderately differentiated products in well-established disease areas, and the priority is to find a way to stand out from the crowd. This requires innovative approaches to unveil insights into stakeholder needs and behaviors that competitors do not have.
  • For roughly 15 percent of launches, the priority will be to establish unmet needs effectively to ensure access to a well-differentiated treatment for a targeted population. McKinsey call these launches “category creators.” Gardasil, launched in the un-established human papilloma virus market, is an example.
  • 8 percent of launches face the substantial challenge of launching an undifferentiated product in an un-established disease area.

Broad strategic steps prescribed:

To address this challenge effectively the above report underscores the need for a systematic approach for the pharma players as follows:

  • Establish unmet needs in a disease area,
  • Develop deep customer insight as a basis for a truly differentiated positioning
  • Land the products safely in the market
  • Maximize launch uptake
  • Use early experiences in the market to fine-tune ongoing launch activities

Conclusion:

Considering the prevailing scenario of ‘Patent Cliff’, coupled with progressively drying up R&D pipelines and mostly unflattering success with the new product launches, how would a company work out its new product launch strategy, is becoming increasingly a critical question to answer on priority.

To appropriately tune a new product in its long-term sales and profit growth trajectory, it is imperative to ensure that the product exhibits its winning trends as soon as it is fired from its launch pad.

This is absolutely essential, as it appears from the above study, around one in three launches has been good in meeting the planned expectations. This makes about two-thirds of new product launches falling well short of target.  It is noteworthy that 78 percent of those new products that fell short in their first year target, lagged in their second-year forecasts too. Further, 70 percent of those laggards did not measure up to the organizational expectations even during their third year in the market.

Thus, any inadvertent mistakes in this area could make the grand finale of intense product development and strategizing efforts over a number of years together with expenses of millions of dollars, unflattering, if not catastrophic, both in terms of top and bottom line score-card of the organization, as is happening more frequently during the last several years.

This trend needs to be reversed with the application of innovative minds and charting the uncharted frontiers, sooner the better, for a healthier global pharmaceutical industry, as we move on.

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.