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Natural Product Formulation and Development


Formulating a health product, whether dietary supplement or food, is a lot more than just picturing a combination of ingredients that go well together.

NaturPro can manage all or parts of the process for natural product formulation and development — from seed to shelf — for dietary supplement and health food products.

 Top 10 Product Development Tools:  Product development requires a ‘toolbox’ of analysis including the following

  1. Financial (costing, budgets, pricing, inventory requirements, profitability)
  2. Regulatory status and safety assessment
  3. Market analysis, positioning & competitive forces.
  4. Ingredient Readiness, supplier verification, availability, quality and cost
  5. GMP’s, specifications, and analytical testing
  6. Clinical substantiation and claims
  7. Intellectual property development and freedom to operate
  8. Distribution channel & sales
  9. Manufacturability and shelf stability
  10. Contract manufacturer advocacy: qualification, negotiation and management

 

 

Food and Supplement Claims with Confidence


Labeling laws and truthful claims are not just critical for protecting the consumer, and they also ensure a level playing field for participants. Even during times of stalled regulatory clarity and enforcement, there is still the ‘golden rule’: do unto others by ensuring product labels are truthful and not misleading.

As we know in this era of alternative facts, it’s easy to make a claim, but harder to verify it with facts and science. (Go science.) But science has a problem. Even when fully developed, it rarely provides the full 100% confidence that may be required to change beliefs and opinions. (Boo, science.)

First example: identity claims. Many are aware that the identity of dietary ingredients need to be stated on the product label, and the specification. What is often missed is that verification through analytical tests to confirm identity are required on every batch of dietary ingredients – a minimum requirement under GMP.

Unfortunately, many identity methods miss the mark for validity and fitness for purpose – also a minimum requirement under GMP which tends to be overlooked. But if an ID method does not detect the presence or absence of common adulterants for a particular material, then how is it meeting the minimum requirement? How is it considered suitable for its purpose? In most cases, more work is needed: an adulterants review, developing and adopting multiple methods that determine a material’s identity, and adequate supplier qualification are all keys to providing a more reliable assurance of identity. The ‘totality’ approach to assuring identity is especially helpful when non-specific or indirect measures are used, like those based on infrared spectroscopy or thin layer chromatography.

Health claims also require scientific evidence. (Go science.) Here the standards are more clear, but not without some confusion. It is pretty clear that the U.S. scientific establishment plus judge and jury has decided that animal data, anecdotes and traditional use are not scientific, and therefore are not sufficient evidence to support a health claim. Past that, there’s some gaps in minimum requirements, and ask ten experts to get ten opinions (One or two studies? Published or not?). But most agree that well-designed human studies, with differences in treatment versus control groups different to more than a 95% confidence limit (known as p<0.05) are the path to health claims substantiation. This arbitrary statistical cutoff can be criticized, too, because when p=0.051 (a confidence of 94.9%), a product is deemed no more effective than placebo. The difference is the line between effective supplement and worthless snake oil. This confuses even most scientists, but it does set a pass/fail that can be evenly applied.

Science is becoming increasingly useful in the verification of content claims. Now that analytical tools can quantify at picomolar concentrations, almost down to the molecule, content claims can be powerful and truthful if investments are made in developing and verifying them. On the other hand, content claims are increasingly policed by consumer groups and class action attorneys, so a failure to verify content claims can be painful. In one recent example, the kombucha tea industry has been hit hard by a series of settlements involving mislabeling of alcohol, sugar and antioxidant content, and exploding bottles. Debate over which test methods were suitable for ethanol (one of the most frequently analyzed substances) led to an industry-wide effort to validate a method specific for kombucha. The validation in kombucha compositions was the last step required in order to rule out the slim possibility that kombucha contained unique matrix interferences that could make it difficult to measure with reliability. As a participant in the project, validation results from our partner laboratories showed a GC-FID method commonly used for ethanol in foods and beverages was indeed fit for purpose. After approval by the AOAC scientific expert review panel, the method is now becoming adopted by the kombucha industry as a standard method.

While not all methods require this kind of validation, the process is the key part to pay attention to. First you need to verify the test method. Then you verify the product against the claim you want to use, with the verified test method. Then you can put the claim on your label. In that order.

Here’s another catch about claims: your evidence is only so good as it verifies the claim. Picture an ingredient made on the same manufacturing line as a common allergen. Is a test report and supplier checklist from last year sufficient on its own to prove that a new shipment you just received is allergen-free? Maybe, maybe not. The best test method in the world will not make up for a lack in understanding whether you should reasonably expect the same results with the new lot as you did before. Verification is not just about testing.

Regardless, for those who are interested in verifying label claims, hopefully we can all agree that there should be rules, and the same rules should apply to everyone. What should also be agreed is that whether claims are truthful and misleading should be based on science and facts, not beliefs and opinions. Go, science!

 

By: Blake Ebersole

Published in Natural Products Insider, 2017

 

Historical Food and Supplement Adulterant List


Historical Food and Supplement Adulterant List

Adulteration of food and agricultural materials has a long history. Below is a list in-progress of references citing adulteration of food and dietary ingredients in recent times (publications in the past ~30 years).  The intent of this list to promote awareness for historical adulterants in natural products. NOTE: This list is for comprehensive and historical reference only.

Access Historical Food and Supplement Adulterant List

New Omega-3 Technologies Evolving


Emerging sources and technologies for omega-3, omega-6 and healthy fats:

We didn’t need to add butter to coffee to demonstrate the importance of fats as energy in the diet, but maybe it helped. The concept that there are healthy fats other than omega-3’s and 6’s may present a challenge to market growth. Fortunately, the quality problems that plagued the sector for years have moved on. We no longer need to worry how to clean up fish oil, and make it taste like key lime pie.  But where to go from here?

Hopefully the benefits of omega-3’s will continue to be found from the hundreds of clinical studies in progress.  But no dietary ingredient exists in a vacuum, and there are ways to further optimize omega-3’s beyond the old standbys.  For example, phospholipids naturally present in krill oil have been shown to increase the absorption of DHA, allowing for a lower dose substantiated for phospholipid-rich krill oil. This is nature’s way of optimizing absorption. Both phospholipids and omega-3 are stored in cell membranes, where they serve similar roles.  It is reasonable to think there might be a benefit to consuming both together, beyond the increased bioavailability. Are there better optimized combinations of phospholipids and cofactors which closer represent the nutrient profile of salmon, and may be even more beneficial?  Perhaps.

Meanwhile, man continues to create products based on nature, inspired by milk emulsions and small intestine micelles, developing ways that (at least theoretically) increase the body’s ability to assimilate nutrients.  But some caution is to be given with the re-emergence of New Dietary Ingredient guidance. If NDI’s are to be taken literally, any dietary ingredient having a different composition than one marketed before 1994 requires a notification to FDA. So, it’s probably a good idea to start putting together the safety assessments that will be required for omega-3 ingredients and technologies that were not around before 1994.

Back to the clinicals. In addition to the hundreds already published, there are more than 250 clinical trials listed on clinicaltrials.gov for omega-3, which are just getting started.  You name the health condition and it’s probably represented.  Add on the current study conducted by the U.S. Army, to determine if krill oil improves cognitive performance of soldiers. Out of all the supplements (and likely drugs) possible for a study like this, omega-3’s were selected.  With all this interest, there must be some evidence that the stuff works.

For product development, in case a high-quality omega-3 source is not sexy enough on it’s own, the literature is abound with examples of combinations of omegas with other nutrients.  DHA with EPA and GLA have led to improvements in multiple studies on people with cognitive impairment.  Look for the cannabis craze to result in combinations of hemp seed oil, rich in both omega-6, to be balanced with omega-3 sources like flax and krill. And stearidonic acid (18:4 n-3) from echium and Buglossoides arvensis may be a cofactor to help improve absorption of DHA and other omega-3’s.

Combinations of omega-3 with ingredients that are not necessarily fat soluble may be trending. In a 2014 placebo-controlled study, a probiotic blend and omega-3 combination increased HDL and lowered insulin resistance better than either alone.  The addition of Vitamin E and C to DHA has been researched in clinical trials, and several studies have observed the benefits of statins with omega-3.  Omega-3 blood levels may also affect whether B-vitamins can slow the brain’s decline during aging.  And their addition with Vitamin D has been shown to improve symptoms in people with mental illness. So there is some basis to believe omega-3’s are able to potentiate the effects of both water-soluble and fat-soluble nutrients, likely in different ways.

Our understanding of the relationships between PUFA, fat metabolism and inflammation has created many connections with pathways regulated by other nutrients. Thinking in terms of focused nutrition, a combination of omega-3’s with other sources of healthy fats such as MCT, at a certain dose and balance could provide optimal brain nutrition for certain people.   The addition of other cofactors along the arachidonic acid and inflammatory pathways, in addition to mediators along the endocannabinoid pathways may provide systemic support for the pathways which rely on a steady stream of fatty acids as signaling molecules.

New sources of omega-3 are likely to pop up as they always have. Perilla, new types of microalgae, and plants like canola bred to produce greater amounts of omega fatty acids are in the pipeline.  And a few consumer product categories are starting to emerge as opportunities for fortification with omega-3. Meal replacement powders and liquids are beginning to see omegas being added successfully, benefitting from new powdering and emulsion technologies.  The infusion of omega-3 into food products like eggs, chickens and even prepared foods has been achieved through integration of DHA-rich algae or flaxseed into animal feed.  Thanks to long-term and growing interest, the omega-3 rich products of today don’t look or taste anything like grandmother’s cod liver oil, but are just as healthy.

By: Blake Ebersole

First published in Natural Products Insider, October 2016

References

  1. http://www.hindawi.com/journals/mi/2014/348959/tab1/
  2. http://www.eurekalert.org/pub_releases/2014-05/bawh-nss050114.php
  3. http://www.ncbi.nlm.nih.gov/pubmed/12837515
  4. http://www.scielo.br/scielo.php?script=sci_arttext&pid=S1676-26492011000400007
  5. http://content.iospress.com/articles/journal-of-alzheimers-disease/jad150777
  6. http://www.hindawi.com/journals/ije/2013/361895/
  7. https://www.army.mil/article/172714/omega_3_study_aims_to_give_soldiers_a_cognitive_advantage
  8. http://www.foodingredientsfirst.com/news/Waitrose-Launch-Omega-3-Rich-Chicken-As-Alternative-To-Unpopular-Oily-Fish.html
  9. http://www.fasebj.org/content/26/1_Supplement/125.6
  10. http://www.ncbi.nlm.nih.gov/pubmed/26793308

Opportunities to Improve Cannabis Dosing and Quality


The safety and history of cannabis consumption for food and medicine is unparalleled as a natural product. Combined with the Internet of cannabis anecdotal evidence, it’s hard to think of something so well-researched, but so poorly understood.

IMG_0893

The science on both the positives and negatives of cannabis is solid and growing. A Medline search for “cannabis” lists 14,000 studies, including 814 clinical trials. In a 2015 JAMA meta-analysis of 37 high-quality clinical trials on cannabis totaling 2,563 subjects, the eight trials which measured its effects on pain found it “very effective.” Evidence of cannabis’s benefits for nausea and vomiting was also found in three clinical trials, mirroring its use in folk medicines for ages. Cannabis was also effective in well-designed human trials for spasticity in MS, improving appetite in HIV/AIDS and wasting diseases as well as ocular pressure in glaucoma.

Regardless, most cannabis patients don’t need a meta-analysis to believe in the relief their medicine gives them. Like it or not, for so many people, cannabis improves physical, mental and emotional well-being during difficult or terminal health issues. And its recreational use by normal, healthy people is overall a low public health risk compared to alternatives like alcohol. Thus, many believe access to high-quality cannabis products for both medical and recreational use should not be out of reach.

However, the usefulness of cannabinoids is often limited by its side effect profile. Adverse events noted in a small percent of subjects consuming high-THC cannabis included dizziness, dry mouth, fatigue, euphoria, disorientation, drowsiness, confusion, loss of balance, and hallucination. The use of high-THC products can be habit-forming, and it remains unclear whether they are beneficial or harmful for people with schizophrenia.

The stigma and psychoactive effects of THC are no help for its adoption as medicine and as a dietary supplement. But many feel that a key reason preventing widespread medical adoption of cannabis is the lack of requirements to analyze and control dosage forms.

Laws in the states where cannabis is legal, and products developed in those markets, have attempted to control dosing better than before. Today, many believe that controlled dosage forms of cannabinoids, including cannabidiol (CBD) are required for any real progress to maximize cannabis’s health benefits.

Another area ripe for improvement is in the analysis of product purity (and impurities). In the states, although all cannabis products are required to list test results from an approved lab on all product labels (representing a step up on food and supplement requirements), the reliability of these test results are in question. In a JAMAcommunication recently published, 75 products from California, Colorado, and Washington State were tested for cannabinoid content. Not surprisingly, 60 percent of products contained less THC than listed on the label, based on strict tolerance limits of +/- 10%.

The cannabis experiment is leading to vibrant debate and rapid change, setting the stage for what is to come. Although many unanswered questions remain, we are starting to see the future of a natural, safe and effective health product that adheres to strict yet sensible standards.

References:
1. JAMA. 2015 Jun 23-30;313(24):2456-73.
2. PMID: 23685330, 23307069, 23042808, 21307846, 22716148

By: Blake Ebersole

This article was previous published by Natural Products Insider in October 2015

Education on Lab and Method Qualification at Supplyside


There are thousands of variations of analytical methods used for natural products.  Not all of them are fit for purpose, failing to meet a central requirement for dietary supplement cGMP’s.

Access slides on Lab and Method Qualification

Identity methods for botanical products are especially problematic, as demonstrated by the mass confusion set off by the NY A.G.

And manufacturers and contract labs are stuck in the middle of a supply chain that can lack an understanding of the source or processing method, which are important factors for labs to determine appropriate methods.

The talk presents challenges and best practices for method selection and validation against established guidance from AOAC International. A process for lab qualification, method development and ‘red flags’ will also be presented.

When: October 5, 2016

Where: Supplyside West at the Mandalay Bay Conference Center

Access the slides here

NaturPro Supports AOAC Official Method for Ethanol in Kombucha


NaturPro Scientific presented method validation data leading to a unanimous vote for adoption of first action Official Method status at the 130th Annual Meeting of AOAC International, September 18-21, 2016.

The Official Method status is thought to be the first method to demonstrate scientific validity for ethanol in kombucha under peer review, and is the result of a truth-in-labeling initiative supported by industry.

Kombucha is a fermented tea marketed for probiotic properties, which is expected to continue 25% yearly growth, to nearly $2 billion by the year 2020.

The validation data has been submitted to the Journal of AOAC for publication.

A preliminary validation study, including data from multiple laboratories, is available here. 

NDI, GRAS and Supplement Safety Assessment


The objective of NDI and GRAS  for supplements and foods is to provide a baseline evaluation of the safety aspects of an ingredient.

FDA issued draft guidance on the NDI and final guidance on the updated GRAS requirement in August 2016. The guidances are likely to require a significant amount of information related to safety and quality of dietary ingredients to be compiled and evaluated by scientific experts.

Four Steps to Compliance:

1. Determine the most likely regulatory status of your ingredient:  ODI, NDI, GRAS or other based on a preliminary review of regulatory status and toxicology data.
2. Compile a master file of all your safety and quality documents supporting the new CFR 117 and the new FDA guidances. Most master files are more than a hundred pages long, including references.
3. Have the master file reviewed for gaps according to the regulatory status. Perform a risk assessment to safety, quality or brand presented from the analysis.
4. Chart a plan of action to meet the requirements.
Toxicology and safety studies are expensive to conduct, so you need to know if your ingredients need to go through the new GRAS Notification process, require a NDI Notification, and also carry any specific risk for adulteration or contamination. Take care of these elements, and you can be fairly sure that you will not be blind sided by regulators, consumers, or class action attorneys.

A pre-assessment is typically conducted quickly to determine the appropriate strategy and level of risk.  Contact us to determine the best strategy for you.

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For more detail, here is a framework of basic requirements for a safety assessment

  1. Clinical, Medicinal and Food Use 
    1. In country to market
    2. Global
  2. Regulatory Status
    1. ODI or NDI (if ingredient used for supplement)
    2. GRAS
    3. Other
  3. Toxicity Summary
    1. History of human consumption in foods/supplements including dosage amount and composition
    2. LD50/acute toxicity/chronic/subchronic toxicity studies
    3. Bioavailability and ADME
    4. Clinical trials
    5. Other (genotoxicity, carcinogenicity, reproductive toxicity etc)
    6. Case reports, AER and Drug Interaction Review
  4. Dietary Supplement Manufacturing Risk Review (or CMC, Chemistry/Manufacturing/Control)

    1. Chemical and Nutritional Characterization
      1. Literature review
      2. Specification, Certificate of Analysis, ID and contaminants
    2. Manufacturing Facility GMP evaluation (self-assessment and audits)
    3. Potential adulterants and their controls

Contact us for more information.

Dose Delivery: Oil Into Water


The gut is by nature one of the best machines imaginable for chemical conversion of food into energy. As a result, the majority of what we consume is changed into something different with incredible efficiency. The stomach begins this process with the pH of battery acid, plus enzymes. Then, the intestines—25 feet long and filled with hungry bacteria and more enzymes— do the rest. Considering the environment, it is surprising that anything we consume actually absorbs into our bloodstream intact.

Bioavailability, often defined as the amount of a compound put into the body compared to the amount reaching blood circulation, is an unexpectedly complex subject. Luckily, the pharmaceutical scientific literature has given us some good tools to understand it adequately.

In order to be bioavailable, a compound must first remain stable and retain its identity in the gut, which is no small order. Assuming it stays intact, its bioavailability can be divided into four main classes, categorized by the Biopharmaceutics Classification System (BCS). According to the BCS system, there are only two chemical factors driving bioavailability: its solubility and its permeability. Water-soluble compounds like ascorbic acid are considered class I (high solubility and permeability), the ideal scenario for bioavailability. However, many fat-soluble compounds such as curcumin are considered BCS Class IV, possessing low solubility and permeability. With the potential of curcumin and its more than 6,700 published studies, this means a lot of opportunity in the face of a lot of challenge.

For Class I to III compounds, dose delivery is often fairly easy to solve. Optimizing these based on pH, particle size, solid dispersions, crystallization or salt forms can be enough to ensure adequate absorption. But what to do about the difficult Class IV compounds?

The water solubility of a compound is based on its chemical polarity, which depends on the electric charge of a compound (given by the presence of charged atoms like oxygen) and its asymmetry. Water (H2O) is polar, because it’s an asymmetric molecule containing mostly oxygen by weight. On the other hand, fats and oils, generally symmetric compounds with a lot of uncharged carbons, are nonpolar and not very water soluble.

The spectrum of polarity includes some compounds called amphiphilic (meaning both-loving) which are able to interact with both polar and nonpolar compounds. As a result, they are ideal to include in many dose-delivery systems. Because ‘like dissolves like’, amphiphiles can dissolve both fat- and water-soluble compounds; detergents like soap, which dissolves grease into water, are one everyday example of this type of compound.

The use of amphiphiles to improve bioavailability has already been perfected in our gut. High-purity phospholipids are the key components used by the small intestine to absorb dietary fat. Phospholipids are also a main part of cell membranes, whose critical function is to separate the cell from its environment while at the same time allowing both polar and nonpolar nutrients to pass through. In the past few years, science has harnessed these unique and interesting properties of phospholipids to better deliver active compounds to target tissues.

To date, thousands of studies have been published on improved bioavailability technologies such as solid-lipid particles, nanoparticles, micelles, liposomes, emulsions, microparticles and others. Phospholipids are one common factor among these technologies, which ultimately stabilize and solubilize compounds of a class IV nature. Curcumin, resveratrol and other fat-soluble compounds all clearly benefit from some of these advanced dose delivery systems.

Yet challenges remain. In the view of the literature and medical use, reliable human efficacy is achieved infrequently; the number of successful human studies using these advanced technologies pales in comparison to the number of successful test tube or animal studies. Why? From a dose delivery view, it is also well understood that there is an ideal concentration of active in the body: too little is ineffective, while too much may be counterproductive. Striking that balance is a difficult task.

The human body and how exactly it works remains much of a mystery, still with vast areas of uncharted territory. And some big differences exist in how we absorb, metabolize and excrete what we consume, due to genetics, diet, what we consume it with and other variables. Plus, each active compound is an individual chemical entity with unique physicochemical characteristics and bioavailability. Hence, the need for good and rigorous science.

Also, our current capabilities and standards for measuring bioavailability are sometimes not relevant to efficacy. For example, bioavailability of fat-soluble compounds is generally measured in blood plasma, because plasma is mostly water-based and the best medium to measure water-soluble compounds. However, plasma data often does not reflect actual bioavailability of fat-soluble compounds, because plasma does not generally attract these compounds like blood cell membranes and organ tissues do. Many dose-delivery technologies work magnificently in the test tube, but may not survive stomach acid or the small intestine intact. And some delivery systems may appear to improve bioavailability but only for an inactive metabolite like a glucuronide.

In these cases, the chemical identity of what we measure in the blood, in addition to what part of the blood we are measuring, proves to be more important than the amount we are measuring. When the science of a bioavailability study is off-kilter, it can ultimately lead to the selection of poor clinical study material and a failure to show efficacy. Good science in the early stages of development is critical, and while oil and water can mix, dose delivery is ultimately just a means to promoting health.

By: Blake Ebersole

This article was originally published in Natural Products Insider in August 2014

 

How To Design a Clinical Trial


Designing and executing a clinical trial that meets scientific and marketing requirements can be a tall order. Lots of variable exist, and often a meaningful clinical study result is a moving target. So study design requires significant expertise in the therapeutic area, and an understanding of market dynamics.

Here are four main questions to ask.

1.) What are the rationale and central questions to the study? There are a number of questions that need answers, but in general, clinical studies should start with one or two central questions, and a reason for why the material should be studied. This results in the development of primary and secondary endpoints. Are you trying to see whether a nutritional product can improve joint pain in baby boomers, or muscle pain in athletes? Because the study design may be completely different for what may appear to be very similar studies.

How the product will be perceived by the market post-study is also important. What study endpoints will allow for solid marketing claims? If your product has a significant effect in the study, will it help to differentiate your product against the leaders in the category? In the drug industry, studies on new products are compared against the “standard of care,” and the approach for supplement clinicals can take the same approach, particularly if the product is not very well differentiated in other ways.  Are there new mechanisms of action or emerging markers that can be added as secondary endpoints, which would help to differentiate your product?

Accumulation of data to support safety and global regulatory acceptance such as GRAS determinations should always be an objective, so any efficacy study is also a great opportunity to inexpensively accumulate safety data.

2.) What is the dose? Often, this is the most challenging and critical question across all drug and nutrition clinical studies. For many products that are complex mixtures of active compounds, pharmacokinetics or bioavailability is unknown or untenable, making dosing a wild guess. In cases where there are only a couple active compounds, bioavailability should be assessed before moving on to clinical efficacy trials.

In cases where bioavailability cannot be easily determined, a dose-response study (using multiple doses) should be performed. Ideally, a dose-response study observes a small effect at a lower dose, and a greater effect at a higher dose. In other cases, a linear dose-response relationship should not be assumed; a higher dose may not work as well (or reveal safety issues) compared to a lower dose.

Market considerations, such as cost per day and number of capsules should also be included in this evaluation. While a randomized, placebo-controlled clinical trial is wonderful to have, if the product never reaches the shelf (or the dose is too high for the consumer to stomach) then the best-designed study is like a tree falling in the woods.

3.) How many subjects are needed for the study to be adequately powered? A minimum requirement today for nutritional products is that the changes in the group taking the active dose must be significantly different than the changes in the placebo or control group. It makes no sense to design and invest in a study that will show no difference between your product and a sugar pill. For some subjective measures such as pain, the placebo effect and inter-individual variation can be very high, due to the subjective and ever-changing nature of pain perception. In this case, the number of subjects required to get reliable statistical separation between the active versus control groups is relatively high. For other endpoints, such as blood concentrations of actives in pharmacokinetic studies, placebo effects are almost nil, and therefore a lower ‘n’ is likely to result in significant changes versus controls.

4.) What is the budget and timeline? Research is an investment, one that can be expensive and time-consuming. For example, if the therapeutic area and endpoints include testing of blood markers, then the drawing, processing and testing of blood samples is a major cost center in the research budget.  Common blood markers such as blood lipids are relatively easy using standard kits, while other less standard markers can require method development and increase costs, and may provide unreliable data that needs to be repeated.

A university-based study offers the independence and clout of world-class clinical studies, but the prestige can be balanced with increased costs and more uncertainty in the timeline, particularly when your study is relatively small and relies on shared resources. While a contract research organization is often faster than a university, this option can also come with greater costs. A research services contract with a detailed protocol and time-based milestones is critical to have in place.

Ethical approval (typically through an Institutional Review Board, or IRB) is also required for all human studies. Some research centers can get IRB approval within a month, while others are mired in bureaucracy and generally take six months or more.

Recruiting also contributes to the study timeline. If you are excluding a lot of lifestyle factors, then your available population is low, and getting the required number of subjects can be costly if not impossible.  Many clinical studies never get off the ground when recruiting is not taken into account.

Lastly, it is critical to do the homework up front and ask a lot of questions. Make sure you have someone in your corner, who speaks the language and is looking out for your best interests. Only then can you ensure the returns on your research investment are maximized.

By: Blake Ebersole

This article was previously published in Natural Products Insider, June 2015.