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Passiflora edulis (Passionflower) flower, seed or vine

by NaturPro in GHC Comments: 0

Location: Karnataka, India

Harvest Season: depends on plant part

Acres: 50

Certifications:
Good Agricultural Practices
Uses Organic Practices
Non-GMO

Farmer name: Sushil G.R.

Family Operated: Yes
Years in Operation at site: 50+

Asking price:

Flower: 300 INR/kg (shade-dried on-site)
Vine (stem): 65 INR/kg (cut and shade dried)
Seed: Inquire

Purchase Material: E-Commerce In Progress

Shipping: FOB Bangalore

Product Listing #: 389174

Article: Regulatory Compliance Systems for Supplements

by NaturPro in Quality Comments: 0

In the U.S., dietary supplements and their ingredients are subject to a patchwork of regulations, industry guidances, voluntary certifications, and audit programs.  With some exceptions, few of our standards have been developed with expert consensus and then broadly implemented by industry. FDA’s dietary supplement Good Manufacturing Practices (GMP) are part of the exception, and have made today’s supplement products generally a higher level of quality than at any time before.

Yet few industry standards are clearly understood, consistently applied, and sufficiently comprehensive to cover all the ground.  One primary example lies in the gap between compliance requirements for dietary ingredients (under food GMP) and dietary supplements, whose GMP framework is derived from that for pharmaceuticals. The underlying litmus test for the level of safety demanded for supplements and foods are different – that of ‘non-adulteration’ versus ‘safe for human consumption’.  Maybe due to the differences, supplement GMP audit programs often tend to overlook the food GMP that governs ingredients. So it is not uncommon for a manufacturer and a supplier to speak completely different quality languages. Audits for supplement GMP are frequently unable to determine to a reasonable degree of certainty whether a particular ingredient, based on its COA, should be expected to meet supplement requirements once it is placed inside a capsule or tablet.

As could be expected, an unintended consequence of this gap is the common practice of a raw material certificate of analysis being simply duplicated as the manufacturer’s raw material specification.  In this scenario, an ingredient specification has been developed according to food requirements, and often without any further analysis or verification, is assumed to meet the requirements of the finished supplement. The end result is a supplement that is essentially of no better quality than the “food-grade” ingredients put into it.

For botanicals and animal-derived raw materials, there is the added dimension of cultivation and processing before they are made into usable ingredients. This is a complicated problem, particularly for a global supply chain of agricultural materials that may or may not pick up contaminants during farming, harvesting, processing, storage or transportation to the ingredient processing facility. These contaminants may not be necessarily listed on the specification or controlled by the food GMP, yet can cause the supplements to which they are added to be adulterated.

Then there are the dozens of standards written for agricultural products, many of which don’t (or can’t) apply to the small family farmer that are a predominant source of botanical raw materials. In addition to recent FSMA requirements for fresh produce (which don’t really apply to dried agricultural materials), we also have USDA Good Agricultural Practices (which are intended for large farms and seldom fully practiced in the U.S.);  NOP Organic (which requires no testing for contaminants like pesticides that may cause a product to be adulterated); independent farm standards  like Global G.A.P. (also intended for large, modernized industrial farms); and dozens of Good Agricultural and Collection Practices (GACP) for medicinal plants that have been independently written by various nations and trade groups.

There are those who say that the mess of standards, the dynamics of industry, and the law of entropy do not support the possibility of a clear and unified regulatory structure.  Yet there are many others who recognize the limitations, yet remain busy sewing the patches together into a quilt that is greater than the sum of its parts.

Fortunately, a number of initiatives are in process or recently completed that contribute to the integrity of our industry quilt, and have provided a lot of free information.  Just in the past couple years:

  • The U.S. Pharmacopoeia and American Herbal Pharmacopoeia have developed a number of monographs and methods for testing dietary supplement ingredients.
  • USP has also developed a Food Fraud Mitigation Database that lists adulterants common for food ingredients
  • AOAC International has developed a number of analytical methods for dietary supplement ingredient potency and contaminants.
  • The NIH Office of Dietary Supplements website has become a valuable source of information and resources.
  • Trade groups like the American Herbal Products Association and American Botanical Council have made enormous efforts to educate and guide the industry on issues around botanical dietary ingredients and adulteration, including a recently updated draft GACP from AHPA, and the ABC-AHP-NCNPR Botanical Adulterants Program.
  • The Supplement Online Wellness Library (or OWL) was established by the Council for Responsible Nutrition, to allow labels for supplement products on the U.S. market to be put into in one place.
  • The Supplement Safety and Compliance Initiative (SSCI) was formed as a broad industry initiative, with wide support from the trade associations, to address some of the gaps for supplements that aren’t sufficiently covered under other standards.  SSCI is led by a number of experienced players in retail, manufacturing and supply, and includes a focus on identity, risk assessment and quality for raw materials.
  • In response to consumer demand, a number of leading retailers, manufacturers and ingredient suppliers have invested significant resources into traceability and quality, and are now able to make meaningful claims to these effects that are not only important to consumers, but also serve as a reliable way to differentiate from the competition.

Today’s movement towards a greater level of education and transparency includes a firming of the gaps, especially where raw material traceability and quality are concerned. Successful companies across the entire supply chain are actively improving and adopting new standards as they come along, building a level of quality and integrity that provides lasting value to their business.  Those who are upping their game are piecing together a quilt of their own, leveraging their quality advantages into claims that deliver marketing value. On the other side, those who continue to rely on ignorance or a lack of regulatory clarity as reason to take no action are increasingly left behind.

In an industry where faceless online product marketers are more common than they should be, and where a list of the tens of thousands of products on the market is just getting kicked off, efforts to fill in the gaps of our patchwork are probably a good thing for everyone.

First published in Natural Products Insider

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.