Is My Product Ready for Clinical Trials?

(This article was published on Natural Product Insider magazine for November, 2009 Issue. http://www.naturalproductsinsider.com/articles/2009/11/is-my-product-ready-for-clinical-trials.aspx)

A clinical trial is considered low-hanging fruit in the dietary supplement industry, yielding immediate marketing value. Other types of data to support claims for a health ingredient or supplement are not as glamorous or accretive to the bottom line. Ideally, consumers want to know whether a product works on them and not just in animals. Regulators even specify controlled human studies are the gold standard for evidence of efficacy of health ingredients or drugs.
Before nutraceutical firms started to look at clinical trials in a big way, product marketers relied on testimonials from satisfied consumers and health care practitioners. Today, companies are increasingly dedicated to clinical trials; however, two types of preclinical research—“Formulation & Analytical Development” and “Animal Pharmacology & Toxicology”—are important, although the investment can seem costlier than the results.


Formulation & Analytical Development
As an example, suppose you have a novel compound from India that you want to market globally. Traditional knowledge and some in-house laboratory data substantiate certain health benefits. Ready to make that claim in most countries? Not without a passport.
The passport is a review of the finished product’s quality. Ingredient certificates of analysis (C of A) provide details on the ingredient itself; however, formulation and production steps ranging from granulation to tableting can impact the compound. Further, novel delivery systems and dosage forms also affect an ingredient’s bioavailability and stability.
On a global level, innovation in novel nutraceutical dosage forms has been slow, although some actives have been converted into forms suitable for food or beverage formulation.
There has been little innovation in new dosage form design such as sustained release or delayed release herbal products, patches, oral release sublingual tablets, etc. On a global level, Japanese firms have converted a large number of actives into functional food forms. But take our example from India. Curcumin, which has been studied for many health effects, has been shown to have poor bioavailability in humans, making innovative formulation or delivery technology a must.
The bottom line—if a finished product is not standardized as it leaves the production lines, stays stable on the shelf and is well available at the target sites of action in the human body, having a hot marketing claim won’t deliver results.

Animal Testing
Some firms may question the need for spending money on animal work if they are committed to investing in clinical trials. Perhaps it is less than ethical to test on animals when human research is equally possible for potentially harmless natural health products, right? Wrong. There is still plenty of research that is possible only in lab animals and not straight away or not at all in humans. Where there are specific safety concerns from traditional use or where the manufacturing process is likely to alter the ingredient dramatically, it is required by the regulators to perform some basic or extensive safety testing in animals before marketing or even human trials.
Even when animal studies are not required by regulations, in vitro and in vivo efficacy studies both offer advantages of screening several ingredients and doses of the same ingredient rapidly and more efficiently in the lab than it would be ever possible in a clinical setting. Moreover, some animal models are available that can elucidate mechanisms of actions which are difficult to reveal in simple human studies. Pharmacokinetic and bioavailability indicators can come out quicker and may be equally respectable as expensive human data.
Also, only having anecdotal data can hamstring the ability to design an appropriate clinical study protocol. Human studies can be expensive, even if off-shored. For clinical trials to be successful and cost-effective, the trial objectives need to be focused. Animal study results can provide this single-point focus to permit the development of a clinical study protocol that is likely to generate a positive outcome. This industry has a history of presumably good products failing in the clinic due to over-ambitious or poorly conceived trial objectives within the constraints of limited resources of time and money.
There are several possible approaches for nutraceutical product development, not one single path as is generally the case with pharmaceuticals. A balanced approach of doing some preclinicals before, during and after the clinical phase of research is prudent. But, each product is different. In some cases, it might be worth running a small pilot human study before doing any preclinical work; however, sample size being small in such a study, one must be prepared to forgo using this data for regulatory purposes. In certain cases, human studies may be more easily set up and in cases such as where “quality of life” is the research endpoint, only a human study will do. There can be many reasons for not doing extensive animal work before getting into clinical trials, but there are not many for avoiding formulation development totally. Typically clinical trials last for longer than a year. A non-uniform or an unstable product going out to human subjects in a study over several months has a potential to create chaos and not authentic and reliable data.
Clinical trial data can be a good tool for differentiating a new or existing product in the crowded market. But it may not be the right time to rush in and pluck this fruit yet. Discuss with your scientific team and outsourcing partners and time it right. An early start on a holistic approach to product development is more likely to yield results in the long run rather than ad hoc decisions on a clinical trial just because the competition has done one. A good dialogue between the preclinical and the clinical teams, set up at an early stage, can be a fair determinant of success. A regulatory expert to guide on research and business strategy can be an added benefit. In this light, contract research organizations (CROs) offering a single point management of the regulatory affairs and preclinical and clinical research programs offer a huge benefit.


Jayesh Chaudhary, is CEO of Vedic Lifesciences Pvt. Ltd., a contract research organization serving the pharmaceutical, phytopharma and nutraceutical industries; contact him at jayesh.chaudhary@vediclifesciences.com .