How the Institute for Botanical Research Furthers Evidenced-Based Naturopathic Medicine

  • Currently, herbs depending on the level of research and claims that it seeks to make can be classified as a Food, Drug, or Cosmetic, which are all regulated by the FDA. An example of this is Vitamin C can be classified as a drug, if it’s delivered at the proper levels and you use a claim that it helps treat scurvy. Is the Institute looking to develop botanical drugs, dietary ingredients, or where is the core focus?
  • What is the importance of the herbal supply chain for the research that you do? How do you think climate change will impact herbs, where they are grown, and their chemical profiles?
  • Nuherbs had the pleasure of working on several potential botanical drugs and the rigorous qualification and quantification process involved. What are some key learnings that you think we can adopt in the dietary supplement spaces with regards to dietary ingredients?

Read the full transcript below and watch the video below. 

Wilson (00:02):

I would like to welcome Bill Chioffi, my great friend. It's a pleasure to get a chance to catch up with you. He's currently in the Rick Scalzo Institute botanical research Institute at the Southwest college of naturopathic medicine and health sciences. What a mouthful. But can you tell us more about the Institute and what it does? What do you guys do over there in this mission?

Bill Chioffi (00:26):

Yeah, absolutely, Wilson. It's great to see you again too. And I look forward to the times when we can get together and I miss doing that with the industry, but I know we're getting close. And so anyway, the Rick Scalzo Institute for botanical research is housed at Southwest college of naturopathic medicine. Yeah, it's a mouthful. And it's part of a transformational gift that Rick made to Southwest college to further botanical research. And so through that gift, we were able to build a molecular biology and analytical chemistry labs and a biosafety level to cellular and viral culture lab.

And so the thought is to further the advancement of evidence-based medicine by looking at cellular mechanisms of actions of plants, safety aspects of the plants by testing whole plant extracts in bioassay models. So in vitro cellular models. And so that's part of what we do. Obviously, there's many different aspects.

We do have the ability to do complete isolation of plant extracts and prepare standards and have standard column fractionation and then different machinery assisted purification of natural products.

Bill Chioffi (02:01):

So yeah, it's very detailed, but I think it's the kind of research that we really need to be doing to understand plant medicines and provide that evidence, right? That everybody's looking for safety and efficacy.

Wilson (02:17):

Yeah. And I think you guys can do quite a bit and I've seen some of your setups, quite impressive. And I think the ability to do contract R and D with people that know plants to come up with evidence, to fit the evidence based model in the US via the prism of what's required by the FDA is amazing. It really is unique for this industry and for the type of stuff you guys can do.

Bill Chioffi (02:49):

Yeah. And because we have the benefit of having naturopathic physicians and herbalists and Dr. Jeffrey Langland, a molecular biologist and former vaccine developer. For years, he worked on vaccine development with his molecular biology degree and he came over to what he said is the light side to take a look at how actual plant extracts have many of these same mechanisms of actions against viruses.

He kind of fell in love with a plant called Sarracenia purpurea which is a purple pitcher plant. And so it's a caribous plant. Very interesting plant. Can't produce its own nitrogen as with other plants, has a hard time with that so it eats bugs to digest those and get a nitrogen source. So at any rate, looking at antiviral capacities of that plant, it really led him to think that, yeah actually plants are very effective at some of these. Bill Chioffi (03:51):

And of course he's looking at in vitro models, but then was able to scale some of those small products up and apply them in small clinicals at the Southwest college campus. So, yeah we use that and, so that came from looking at a treatment that was purported to be used for smallpox in the 18 hundreds using that plant.

So, yeah. Interesting work for sure, Wilson. It's a different job than I've done in the past, but like you said, knowing the plants and working with brands that understand the value of the efficacy of their products, because we are so limited in what we can actually say, which is a good thing in some ways. The DSHEA restrictions give us the freedom to continue to sell these, but really at the end of the day, the product has to work right? For people to come back and try it again.

Wilson (04:47):

Yeah. I think like you said, the key is efficacy, right? And we are limited in what we can say and not, right? I think let's sort of go, take a step back and look at what the FDA actually governs and how, what product classes are at a very high level, right? There's the food in the F, which is the F in FDA. Drugs is the D and then association, but it also has a cosmetic. So it's the FD and C act actually.

And botanicals can be used in all three categories. Under food, it would be used as a food or as a subclass, dietary supplements, which many of us are extremely familiar with and that's the part of the industry we're the most familiar with. But there's also under drugs there's this class of drugs called botanical drugs, which is different from our traditional way of thinking about drugs.

Wilson (05:40):

And I think that's really important because now if you want to say that your product cures X or treats X, you can say it, if you meet those requirements. I think that's sort of the interesting part of it that we sort of don't really see day to day being discussed. And is the work you're doing there more focused on this botanical drug model, dietary ingredients, or what is the core focus or is this, as long as it involves plants and the areas you touch, whether molecular biology, safety, in vitro, the classification to you as a researcher, doesn't matter? It's just the rigor you have to maybe put behind some of the studies and the costs that comes with that rigor.

Bill Chioffi (06:30):

Yeah, exactly, Wilson. And so given that there are these different classifications now, and starting in 2004 with an initial guidance from the FDA on botanical drugs, and then them coming back and sort of revising the addition in 2016. And so in between that time, I think there's been something like, maybe since 2018 or so, statistics say over 800, some odd investigational new drug applications, which is kind of where a botanical drug starts with an IND application.

And of those 800, there've only been two botanical drugs that have hit the market. And so basically, in defining what they are, we can see how they are different or not than dietary supplements, but they do allow you to make a very specific disease related claim because you're going through basically the same type of clinical outcomes that you would look for, for safety and efficacy with a drug trial.

Bill Chioffi (07:41):

The characterization of the starting materials is kind of where the major differences are and since we don't have much time in this, but there have been some really good, actually on the sustainable herbs program, which you and I both volunteer for, I know Anne was archiving. So there's a great presentation there, which can give people much more information.

Wilson (08:06):

Yeah. And if anyone, after listening to this wants to know more about botanical drugs and want to hear an episode just focus on that, I have a person that's quite knowledgeable in that went through always to phase two in the botanical drug model and were able to work with them and the rigor and the quantification process of the starting material is just amazing. And the rigor and the thoroughness that's required is this on a whole different level.

What are some key takeaways of learnings you think we can learn from that model adopted to dietary supplements in regards to, to make sure that our product is consistently efficacious? Because we know it's not how we use something because there's less science or historical learning and documentation of this efficacy. But it's really, if you give someone something that doesn't have any potency to it, of course it's not going to work or you don't give them high enough dosage or whatnot. But what do you think we can learn from the botanical drug model and adapt to the dietary ingredient space?

Bill Chioffi (09:23):

Yeah. I think the biggest learnings, Wilson, are starting with the beginning of your supply chain and being able to validate the raw materials from an identity standpoint through their development, into an extract. And what's interesting about the botanical drug development process is that they don't actually require you to fully characterize the extract or prove mechanistic function.

They suggest that it's very good to do that and I would think that anyone with a good application would do that, but they're really looking for the fact that they are close to what was used traditionally, because especially if you can prove that this has been a traditionally used formula or combination, and let's not forget that once you add two herbs together, it's very complex, what happens with the chemistry and if you add three or four, it's even more complex. So in a formulation, it's something to consider.

Bill Chioffi (10:31):

So, the topical botanical drug from green tea developed in, I think it was 2006, right? That was about the first one. Very specific use for genital warts. And then the second one, another very specific use from croton lechleri, the sangre de drago or dragon's blood, it's called Crofelemer, Fulyzaq, Mytesi. There's been some different names, but the preparation is basically taken to control symptoms, diarrhea from aids and HIV infection. So again, a really specific narrow window of usage for that, validated by the clinical trials. So I think what's interesting is that these botanical drug products do have to be botanicals. And in the 2016 revision, the FDA defined further what a botanical would be. And so it could be plant material, right? It could be microscopic fungi. That's another part. Could be algae or it could be a combination thereof.

Bill Chioffi (11:44):

So broadens the definition a little bit of the definition of botanicals, as opposed to saying herb, right? So little distinction there, but the lessons that we can learn, the same things that you should be doing in your dietary supplement botanical manufacturing process are some of the most important things here, like starting with your identity program and the validation of your raw materials, not just for the purity, meaning it's free of impurities, like heavy metals, pesticide, so forth, but then, the identity that it is what you say it is.

Bill Chioffi (12:25):

You and I have had many discussions about identity and the rigor that that takes and the seasonal variations in plant material that are the same exact genus and species that present differently, depending on when they were harvested and where they were harvested and how they were harvested and what was going on with the weather and what was going on with the farmer and so it's complex, but those are the things where we need to know what we have and we need to know in a basic way, what it does validated by either the tradition, but best to be a blend of the tradition backed by evidence based science.

Wilson (13:07):

Yeah. And I think one of the things that we've been talking about since we've known each other is the supply chain. Right? And I think a lot of the repeatability of the studies that are done comes down to the rigor of how they characterize the material in the supply chain. Right? And you can't reproduce something if they just tell you it's an extract of ginseng, right? Of Asian Ginseng, it needs to be a little bit more thorough before you can do it, I think. And what do you think is the importance of supply chain for research? Evidence based research, and for the repeatability aspect of things, how important is that?

Bill Chioffi (13:53):

I mean, it's of fundamental importance because we start with these crude raw botanicals. And so, even in our research lab, when we have our herbarium set up, we have to make sure that if we're running any of these things through bioassays even with using standard, just ethanolic extracts of them, that we've had identity testing done. And so we outsource that to a mutual friend just because we want that third party validation. So, we outsource that to Alchemist and we have the ability to do that. We have an LCMS, we have TLC tanks and plates and so forth, but we would prefer to have that done outside. Then we start our herbarium from there. So the same way that we would test the activity of those extracts, we've got an identity validation and we've logged in the raw material.

Bill Chioffi (14:48):

And then we're building to have voucher specimens on file for the plant as well. And then adding the files on microscopy as things go on, but so if we do a small pilot scale extraction in the lab, the very next conversation I have to have as a business development person is, with our ended partner or whoever we're working with is, where are we going to go to get this manufactured to your exact specification? Because oftentimes what we're developing may be a little different

than what's standardly available on the market. But we certainly can start with pre-extracted material and do testing on that. And that could just be duplicated, but oftentimes we like to start with the whole botanical and do a range of ethanolic extracts to test activity. We found some very interesting results from that, actually. I know you have good SOPs throughout your manufacturing process so that if there is a deviation from the finished product in any way, safety or not, you have a way to go back and track where the problem was.

Wilson (16:05):

Yeah. And I think, based on our conversations in the past, we added that capability on new herbs and really to take our botanical expertise and being in touch with the growers and wild crafters and taking that ability now to do the R and D component of it and where we would work with someone like you or a similar facility to do that lab scale work. Right? And then from lab scale, we have partners that allow us to take that lab scale work, to go to pilot scale and pilot scale to go to production scale. And there are challenges at each scale that are unique to that. And just because you could do it in the lab, doesn't mean you could efficiently do it at scale. And I think that's the know-how, right? You have to have a lot of experience in extraction before you can take something, the concept, proof of concept is done in the lab, but then how do you scale that? Right. It's very important.

Bill Chioffi (17:05):

Yeah. And putting it back into the model of, let's say you were developing a botanical drug, you'd need the actual transparency through the entire process, from where the material was grown to where it was shipped to and processed and through the whole chain of custody, which really should be done anyway. But the manufacturing process as well has to be well documented. And so I think, like you said, the intangibles here are beyond just the logistics of getting that much material to make a product for that long or the sustainability or the responsible sourcing and ethics behind raising these plants during climate crises around the country and around the globe, actually. So that's a discussion for another time.

Wilson (18:05): Yeah.

Bill Chioffi (18:05):

But the fact remains that it's harder and harder for farmers, no matter what the crop is that they're making to make a living off doing that. And when you go down to the level of very specialized crops that we're talking about, then the problems compound.

Wilson (18:24):

Definitely, and I look forward to continuing this conversation and many conversations with you in the future. If you're at the supply side, if it happens, we will have an in person panel and maybe longer discussion amongst friends and then we can really dive into this topic of climate change and its impact on herbs. Thank you so much for joining us, Bill and it was a pleasure as usual. And thank you once again and hopefully we'll see you soon.

Bill Chioffi (18:54): Yeah. Yeah. Always great to see you, Wilson. Thanks a lot.