On the podcast today we have David Schoneker who is currently the President of Black Diamond Regulatory Consulting, a consulting firm specializing in providing regulatory and quality consulting for the pharmaceutical, dietary supplement, food and related industries.
The firm provides expert advice for difficult problems and training on excipient and food additive regulatory, quality and supply chain concerns. With over 45 years of experience working in these areas, Dave has developed strong networks with trade associations, regulatory agencies and pharmacopeias around the world. He is also an Adjunct Professor at Temple University’s School of Pharmacy in their RA/QA Masters Program teaching courses in Global Excipient Regulations and the Regulation of Dietary Supplements. Prior to this, Dave was the Global Regulatory Director of Strategic Relationships at Colorcon, Inc.
Enjoy!
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Previous episodes:
https://www.qualio.com/from-lab-to-launch-podcast
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Music by keldez
On the podcast today we have David Schoneker who is currently the President of Black Diamond Regulatory Consulting, a consulting firm specializing in providing regulatory and quality consulting for the pharmaceutical, dietary supplement, food and related industries.
The firm provides expert advice for difficult problems and training on excipient and food additive regulatory, quality and supply chain concerns. With over 45 years of experience working in these areas, Dave has developed strong networks with trade associations, regulatory agencies and pharmacopeias around the world. He is also an Adjunct Professor at Temple University’s School of Pharmacy in their RA/QA Masters Program teaching courses in Global Excipient Regulations and the Regulation of Dietary Supplements. Prior to this, Dave was the Global Regulatory Director of Strategic Relationships at Colorcon, Inc.
Enjoy!
Qualio website:
https://www.qualio.com/
Previous episodes:
https://www.qualio.com/from-lab-to-launch-podcast
Apply to be on the show:
https://forms.gle/uUH2YtCFxJHrVGeL8
Music by keldez
hi everyone, and welcome to From Lab to Launch by Qualio I'm Meg, your host. Thanks for tuning in today. Before we jump in, we'd love it if you rated the podcast and shared it with any of your science nerd friends. We know you have some. If you'd like to be on the show, please fill out the application link in the show notes. We're grateful for all the interest we've had lately. Today our guest is David Schoneker, who is currently the president of Black Diamond Regulatory Consulting, a consulting firm specializing in providing regulatory and quality consulting for the pharmaceutical, dietary supplement, food, and related industries. The firm provides expert advice for difficult problems and training on excipient and food additive regulatory quality and supply chain concerns. With over 45 years of experience working in these areas, Dave has developed strong networks with trade associations, regulatory agencies, and pharmacopedia around the world. He is also an adjunct professor at Temple University School of Pharmacy in their RA/QA Master's program, teaching courses in global excipient regulations and the regulation of dietary supplements. Prior to this, Dave was the Global regulatory Director of Strategic Relationships at Keller County Inc. Without further ado, let's bring David.
David R. Schoneker:Welcome, Dave. How you doing, Meg?
Meg Sinclair:Great. So to get us started, Dave, can you tell us about the start of Black Diamond regulatory consulting?
David R. Schoneker:Sure. You know it, uh, I'm a, I'm a, I'm a big time skier and, uh, have a love of skiing all my life. And, uh, when I, uh, retired from Colorcon and, uh, started, uh, started consulting, I was trying to figure out the name of my, uh, firm and, uh, uh, my daughter sort of, uh, gave me the idea of, uh, working something with my love of skiing into the name of the company. So anybody who's a skier understands, uh, what double black diamonds mean. And, uh, obviously, uh, I have a firm out of expertise in these areas, um, that I like to, uh, be able to help, uh, you know, clients with very difficult problems that they have, uh, including the one that we're talking about today.
Meg Sinclair:That's great for our non-skiers. Do you wanna tell them what black,
David R. Schoneker:black diamonds mean? Good, good, good point. Yeah. Yeah. You know, black diamonds stand for expert trails, uh, double black diamonds, uh, which is my logo, essentially. Uh, stand for, you know, uh, you know, sort of super expert trails. Uh, some of the most difficult on the mountain.
Meg Sinclair:Very good. Um, so one of the things we keep hearing about in the news and, um, our concerns around titanium dioxide, um, in the news, can you tell us a little bit about what titanium oxide is and how it's used in the food and pharmaceutical
David R. Schoneker:applications? Uh, absolutely. Yeah. Titanium dioxide, uh, outside of water. Is probably the most used, uh, excipient in pharmaceutical formulations. Uh, it's also, uh, a big time ingredient in many food applications as well. Um, it is a pigment, it is a white pigment, uh, and it's got some very unique properties. Uh, That really no other material that you can utilize in pharmaceuticals, um, uh, have the kind of properties that Tio two has, and we will talk about those as we go forward a little bit. But it, it, it tends to be used as, uh, not only a white colorant and white pigment, but in opacifier. So that even if you have, uh, different colors on a coating, let's say on a, on a tablet, uh, or in a capsule, you need to opacify that color and so, you know, to, to make it bright and also make it, uh, so that light doesn't just, uh, trans, uh, so it's not transparent, if you will. Um, and that provides, uh, protection to pharmaceuticals in, in terms of light stability controls, et cetera. So, you know, Tio O two is one of the, uh, you know, what a lot of people tend to refer to is sort of one of the perfect excipients that have many different uses, not only for coloring and opacification in pharmaceutical products and food products as well. But also to really protect the a p i. So many APIs are light sensitive, uh, and Tio O two is one of the main ways that you can protect, uh, the light sensitivity of the a p I. So it, it provides a lot of stability to drug products and because of that, it's been used extensively in literally thousands of drug products all over the world and many, many food products and dietary supplement products as well. Are
Meg Sinclair:there similar ingredients that can provide the same type of properties as titanium
David R. Schoneker:dioxide? I. Nope, there is nothing that you can use in pharmaceuticals that comes anywhere close to the properties that you have with tio two. There are some materials that can be used as alternatives, um, in some cases, but they're by no means, uh, substitutes for t o two, and they don't come close in terms of the opacification, uh, or light protection that they can provide. So the answer is really there, there aren't any real alternatives that are viable in all applications. In some cases, there might be materials that would provide something that I would call good enough, but certainly not the best in terms of their properties and the way they're used. Okay.
Meg Sinclair:So this has really been the gold
David R. Schoneker:standard thus far. Absolutely. And that's why it's been used, um, all over the world in, you know, almost anything that, you know, has any kind of color in it. Uh, you know, whether it's white colored, you name it, um, uh, you know, uh, if it's coated, if it's a, a capsule, any of that has T two and it, uh, historically, um, you know, it's been in most products on the market. Interesting.
Meg Sinclair:So there's been a lot of news coming out of Europe. Can you explain what has happened there recently with, um, titanium dioxide in
David R. Schoneker:foods? A a Absolutely. Yeah. There, there, there's, there's a lot of press that people hear about and they only get one side of the story. And, and unfortunately, you know, uh, for, uh, you know, the consumer out there who's not a, a toxicologist or a scientist, they don't always understand, you know, some of the details. But you know, what has happened, really, uh, it, as far as I'm concerned, uh, it, it's, it's sort of a travesty what's happened in Europe. Okay. Uh, i, is that, you know, um, the European, uh, uh, food Safety Authority was charged with reevaluating the safety of many different food and and color additives. Uh, and back in 2016, they started a reassessment of titanium oxide, and they looked at all the, you know, newer studies that were out there, et cetera. Um, and their initial evaluation was, I. We don't see any problems with titanium dioxide. However, there's a few data gaps that, uh, we feel we'd like to fill. So they put out a call for data to the industry. Uh, the industry responded, spent millions of dollars on new studies to fill the gaps that that sso, which is the abbreviation for, uh, the European Food Standards Authority, um, that FSSA requested, did every study they, they asked for. Okay. And, uh, you know, supplied that data as it was coming together. Uh, FSA looked at this and reassessed it several times. Um, and during that process there was a study that was funded by the French government in France, um, that, um, uh, had a very poor study. Design should have never been considered as. Uh, having any credible data, as far as I'm concerned. And, and, and as you'll hear, many toxicologists all around the world. Um, but unfortunately, uh, in France, uh, there's, uh, you know, I'll call it in, uh, over precautionary concern about the presence of nanoparticles. And, uh, in, in many materials and, and in titanium dioxide, there is a certain portion of, uh, the pigment that is nanoparticles. That's actually what gives it, its unique properties. Without that, it wouldn't have the properties, right? So the other thing is those particles have always been present in the t o two, that every person on the planet has been eating at significant levels or taking in drugs pretty much every day of their lives for the last a hundred years without even one person ever having an adverse effect. It's ever been tagged to titanium dioxide, however, This very poorly designed study in, in France, um, indicated some potential concerns, and I won't go into the details here for this audience, but, uh, they, they indicated some potential concerns, uh, which got a lot of media attention and a lot of political attention, especially in France because they're worried about nanoparticles. Okay? Um, so what happened was, uh, France believed there was a problem. Now remember, the French government funded the study also, so that's important to to stress. They funded a study and they had a poorly designed study that got a certain result on something that they were nervous about. Okay? Uh, so. Um, France basically wanted to ban the material based on this question that came up. Uh, they went to ssa who was reviewing all of this data during this reassessment. And even ssa, the European Food Safety Authority, looked at the data from France and said, there is nothing here that we believe should change our position that t o two is safe. Uh, and in fact, we're gonna continue its use and maybe ask for a few additional studies to fill some data gaps. Okay. Um, which industry did okay FSA continue to say it was safe and they continued to say it's safe after multiple times that France asked them to reassess the data and new data, et. Uh, uh, you know, right towards the end when everybody in industry was expecting that FSA had completed their evaluation, that they were going to provide a acceptable daily intake for this material, which was what their goal was, they changed course at the last minute and basically said, well, we've now looked at all these studies on truly nano grades of t i o two that actually have nothing to do with the pigment grades that we use in foods and pharmaceuticals. They're designed for catalyst use in the chemical industry. But, but they looked at that material and they said, oh, there's more data gaps now. And because we now have questions, we can no longer say Tio O two is safe. Okay? Now again, those, that wording's important saying that we have data gaps and we can no longer say it's safe is not saying there's a safety problem. Okay. Yes. It's simply saying we have some uncertainty and some questions. Now, what they should have done is what they did back in 2016 or 17, when they asked the industry for more data to fill the data gaps. They didn't do that. They published their opinion and said, we can no longer say it's safe because there's data gaps. Well, the politicians in Europe took that to mean there's a safety problem. We have to ban this material. And very quickly moved towards banning the material. Uh, so this started in France. It became political. And what I would say the term that I tend to use in a lot of my presentations on this is, uh, uh, political toxicology got into the mix. Okay? And this really doesn't have anything to do with good science and a real safety problem. It has to do with. What happens when negative media comes out that's not based on good science and it gets beyond the science. Okay. And so ultimately, after all of this, and I know I've gone through a extensive discussion here, but it's important'cause it sets up the rest of our conversation. Um, essentially Europe decided to ban, uh, uh, titanium dioxide for food uses because that's what they were evaluating it for. Okay. Um, and that ban went into effect, uh, in, uh, 2021, uh, for all food products that could no longer be made with titanium dioxide in, in the European market. And that required companies to have to do massive reformulations of many, many different food products. Um, and in many cases, um, the products that, uh, used alternatives, uh, maybe were, again, I'll call it good enough. But not necessarily as good as what they could be with titanium dioxide. Now, the food industry is a lot different than the drug industry, but I wanted to answer your question about foods and what happened in Europe so far. Are there any really
Meg Sinclair:good studies that address or identify safety concerns with the use of titanium dioxide in foods and drugs? Is there anything on,
David R. Schoneker:on? Well, that's, that's a really good question. And, and, and when you look at it, there are, you know, especially since this happened, obviously more studies were done both by the industry, by, uh, people who, you know, the NGOs and, and other groups that are now fired up against this material, et cetera. And you'll find that there are some studies out there that, you know, claim. There's some issues, but we've looked at these in detail and essentially there is no good design study that has any scientifically credible information that actually shows a real safety concern. Uh, there are many new studies that the industry has funded, uh, to answer those uncertainties and those questions that came up. And those studies are underway. Uh, and some of'em have been completed. And of course, you know, they show what we expected, that there's no problem. Now, there's some still going on, but there was a specific study that was done, uh, at, uh, university of Nebraska and Michigan State University ran a major study. Basically the study in France that started all this was the, the, the author's name was Batini. So we call it the Batini study, okay? Mm-hmm. Uh, so what, what, uh, Nebraska and Michigan attempted to do was to try to see could they replicate, What happened in that study to see whether or not actually there was an issue or not. Okay. Which is, you know, what you do with good science, you try to make sure that, uh, you know, that you can replicate these things. They, they put together an extremely well designed study to try to answer all the questions about that Batini study as to whether, you know, we should trust it or not. Right? And I'm happy to say after Nebraskan, Michigan finished their study, it came out totally clean, not validating any of the results that Batini had or any of the question marks that Tini had brought up in his paper or their paper I should say. And, uh, so, you know, that's just one study that that is out there and that's published and there's been several others done and they all keep coming up clean. Now, this is not a surprise. Like I said, this material has been ingested by probably every human on the face of this earth for their entire lifetime. Um, With no effects that anybody's ever actually seen. So, you know, short answer to your question, no, there's no credible science that justifies that there's actually any safety problem with TIO two. Now, unfortunately, because of the way the media has gotten out on this, a lot of people don't believe that. Um, you know, there's a lot of, uh, it, it, I'll use today's, uh, vernacular here. There's a lot of fake news out there about TIO two, but at the end of the day, there is no real safety problem with this material that's been demonstrated. And there are continuing ongoing studies to continue to reassess that. Reevaluate and verify that that's true.
Meg Sinclair:So thinking of the food ban in Europe, does that have any impact on dietary supplements?
David R. Schoneker:Yes, it does. Um, pretty much all dietary supplements in Europe are considered food products, so this automatically had an impact on all dietary supplement products that are marketed in Europe. Uh, and, um, uh, uh, again, a lot of people had, well they had to do one of two things. They had to either try to reformulate to something as best as they could with the alternatives, but that doesn't always work. Okay. And in other cases, products were withdrawn and essentially no longer marketed in Europe. Still can be marketed at most other places in the world. But, um, you know, they lost access to some of those products because there was no economics that would drive that kind of reformulation effort, uh, for certain types of products. Um, so there, there's already been an impact in Europe on dietary supplements.
Meg Sinclair:And we expect to see further impact on pharmaceuticals next
David R. Schoneker:in, well, that's, that's, that's the, that's the big hinging, uh, question right now. Because what happened was when this ban, uh, was put in place in, in Europe, it was put in place specifically for foods. But the question got brought up by the politicians and the NGOs. Okay. Uh, hey, this stuff is used in medicines too. We should ban it there as well. Uh, and fortunately, uh, the European Medicines Agency, uh, you know, uh, realized the impact this would have on pharmaceuticals, which we, we'll talk about is, is huge. Okay. And they, and they gathered information from industry and from other sources and, and basically went to the European Commission before this decision was made and said, look, you know, there, there is lots of information showing that this would create a, a, you know, a lot of. A lot of issues for pharmaceuticals. We don't know if it's even possible what the impact would be, what the potential implications to drug shortages and everything else would be. Um, and so they, they basically asked for a delay to allow for further evaluation. So what happened was when the European Commission banned TIO two for foods, they basically gave a three-year extension, uh, for pharmaceutical use of TIO two to allow the e m a to gather further information from the industry and their own sources, uh, as to what the impact would be to try to extend this, uh, band to try titanium dioxide and whether it was feasible or not feasible, et cetera. They, uh, however, basically said during that time period, they encouraged the industry. To, you know, look for alternatives, try to use the alternatives, try to move away from Tio O two. Again, all this is based on the fact that there's really no safety issue, but they were encouraging this because of this belief. Uh, uh, you know, again, remember this became very political, not based on science at, at, at several points. And, um, uh, essentially we're encouraging industry to do everything they can. Okay? So we're in that time period right now, and we're, essentially what will happen is the, uh, European Medicines Agency is currently gathering information industry and others are supplying a lot of, uh, answers to questions that they have and supplying information about, you know, uh, you know, what, what really, uh, are the issues with trying to use alternatives? Are they even possible in some of these applications? And then ultimately, what would be the impact on the drug supply if somebody tried to go forward? With, um, with a ban, uh, in Europe on this. And, um, so that the timing on that is that the, uh, European Medicines, uh, agency, uh, must supply a report to the European Commission, uh, by April of 2024, uh, with a recommendation as to whether or not they feel that the, the ban should be extended to pharmaceuticals, uh, or not. Alright.
Meg Sinclair:That's less than a year away, so that'll be interesting to see what happens there. Oh, yeah. As far as alternatives, what I know we said not much exists. Is there anything that they can use? Um, As an alternative in drug formulations, or do they need to think about changing packaging
David R. Schoneker:for safety? Well, good question, and, and you know, uh, like I said, there are some alternatives that people have been exploring. A lot of work is going on in this area, you know, to try to find something in case a ban would happen. Uh, and, uh, you know, probably when you look at the alternatives, uh, probably one of the best alternatives, and it's not good, don't get me wrong, but one of the best alternatives, uh, are things like calcium carbonate. Okay. Uh, and, um, in some applications where you're, you're, you're gonna have a, a color involved, iron oxides can sometimes, uh, be utilized. There are some other materials, certain types of rice starches, uh, something called is molt, some tri calcium phosphates. These are all materials that people have been trying to use or use in combination to try to simulate the properties of two. To the best degree possible. Now, that said, just to give you an idea of the difference, uh, I said calcium carbonate probably has the best opacification properties, uh, next to Tio o two of the things that are available now, again, we're only talking about ingredients that are approved for use in foods and drugs, not, you know, pigments used in the pain industry or, you know. Mm-hmm. Whatever. Mm-hmm. Um, but um, to give you just an idea, there's something we call contrast ratio, right? Which really tells you sort of how opaque something is. Uh, and, and if you look at titanium dioxide, uh, and the way we measure this is you make up a, a coating and you, you make a, a sort of a draw down on a, uh, a card that's white on the top and black on the bottom. And then you look for what the differences are, where you see the break, you know, how opaque do you see that black under there or not. And there's a way of measuring that with a spectrophotometer, and you determine that what's called this contrast ratio and that, and so a titanium dioxide has a 90% contrast ratio, which means it's almost totally opaque, okay? Mm-hmm. Calcium carbonate. Next best thing 12. Okay. Wow. So like, so you're, you're talking like, you know, like 10 times less, nine or 10 times less. Mm-hmm. Uh, in terms of opacity. So you can start to see where. If you're gonna try to use that as an alternative, uh, you know, you're not gonna have any of that, uh, same kind of opacification. So, so to give you an idea of what that actually means in practice is if you're using, let's say you're making a, a pharmaceutical tablet, and, you know, most tablets these days have coatings on'em with colors or white or whatever. Almost all of them. Half titanium dioxide, unless they've been developed very recently with somebody trying these alternatives. Okay? Uh, and so a, a typical weight gain of the film coating on a tablet, uh, would be what's called a, you know, a 3% weight gain, right? So, and with a titanium dioxide. Coating you can get by with only adding a 3% weight gain and it gives you total opacification to anything that's underneath. And why is that important? Many tablets are colored or have speckles or you know, whatever. Like if you break a tablet open, it's not always white. Sometimes it's right if it's, if it's white, those are the cases where maybe the alternatives might work because you don't need as much opacity. But a lot of tablets might be yellow or brown or speckled. Uh, think of a vitamin tablet. You know, many times they're very speckled, et cetera. Uh, and so you have to hide that. You have to have opacification so you don't see the color, but also you're providing appropriate opacity to give light protection to that a p i, which is the most important part of this, right? If you get away, and most people do with a 3% weight gain of a typical Titan, a titanium dioxide coating, if you have a calcium carbonate, uh, coating, some of the best ones that have been developed to date by some of the best companies, um, you're probably talking anywhere from an eight to 10% weight gain you're gonna have to put on to even get close to what you had with titanium oxide. It's still not gonna be as good, but you might, depending on the, the, the, the surface of the tablet, you may get by. Okay? Now think of that. You get by now with 3% weight gain of the coating, and now you're talking, let's say eight to 10%, like three times the amount of the coating has to be added. Okay? That means it takes you three times as long to make the product. It changes the thickness of the coating by three times. So all of your analytical methods that you had, and this might tie into Yeah. Lio as well. All the analytical methods that are validated. Okay. On drug products today, throw'em out the window because they're based on the tablet that exists today. If you change an existing product to now have three times as much coding, most of your dissolution methods, most of your analytical methods, your assays, everything is gonna have to be redone revalidated. So think of that implication. Mm-hmm. You're gonna have all these manufacturing time, uh, you know, costs and, and, uh, implications that go in. Um, and you're gonna have stability implications.'cause many times if you do have a life sensitive, uh, uh, a p i, you might have to shorten the shelf life. Okay. So all of those sort of negative implications, you know, from an operational standpoint with, with material would come into play. At the end of the day, you still have a product that is not gonna be of the quality that existed before, but you're gonna have put an awful lot more cost into it, which of course is going to have an impact on drug pricing. Right. And, and you know, obviously right now nobody wants to hear about drug pricing going up. I guarantee you that's what'll happen if this span were to take place. So that's one
Meg Sinclair:impact on patients in the pharmaceutical, in industry, um, you know, analytical methods that are validated, getting thrown out the window, prices going up. What other impacts would we expect to see if this span were to take
David R. Schoneker:place? Well, and, and, uh, you know, uh, this is, this is, uh, the scary part, okay? Because the bottom line is just in Europe alone, there are 91,000 drug products on the market today that contain titanium dioxide, 91,000. Okay. Just think of that. Okay. Now, if TIO O two were to be banned, that means that 91,000 drug products have to be reformulated. Okay? Now you think in the drug world, what it takes to reformulate an existing product, okay? Not only redoing all the developmental work, the stability work, the validation work, all the analytical validation work, then you've got the regulatory filings. All of these changes would be a qualitative and quantitative change to the formulation, which means in Europe, that probably would be a type two variation. Okay? Type two variations are significant regulatory submissions, post-approval, change submissions, and even have a fee to do one, it costs$103,000. Just for a fee for getting e m a to look at it. Now, that's just a filing fee, not all the costs of doing all the studies and the revalidation. Okay? So, um, you know, 91,000 products would have to go through that. Now the big question comes, well, what would that really mean then in terms of cost? Well, some analysis has been done on that. The expectation would be, it would cost between one and one and a half million euros for every product that you would have to reformulate if you can and remember some of these products, you're not going to get, uh, you're not gonna be able to reformulate and get a same product, right? Uh, you know, I've talked primarily about immediate release applications. If you start thinking about modified release applications, most of them depend on the coding, or at least a lot of'em to release the drug. So now, if you start putting more coding on. You can't achieve the same release rate, right? So there's technical implications, but then you get into all of these operational instability related things, filing costs, et cetera, one to one and a half million euros per product. So if you were actually going to try to reformulate all 91,000 drug products, that even was possible, okay? You're talking about, uh, approximately$32 billion that it would take to make this change, okay?$32 billion. Now, I guarantee you there are an awful lot of medical issues we have out there that could provide a lot more patient safety benefits for$32 billion than spending it on something where there's absolutely no improvement in safety risk to the patient, which is what would happen here. Okay? Yeah. Uh, so the reality, getting back to your question. That, those are the facts. Okay? That's what it would take if there were to be a ban. The big question comes, if you're a pharmaceutical company, are you gonna reformulate? Okay? And, um, you know, the economics are gonna have to work. The economics ultimately will dictate whether somebody reformulates or not, okay? And I guarantee you many products, there will be no economics to drive such an expense, okay? Especially if TIO O two continues to be approved in other parts of the world, okay? Where the product you currently have is no problem, right? So are you gonna really reformulate and have a separate product for the European market go through all this expense? No. The answer is you are only gonna reformulate products where it makes economic sense. And what that means is all of many of your older products, Many of your low margin products, many of your niche products, your orphan drugs, drugs for pediatrics and elderly, uh, that are small volume products, there's gonna be no economic justification. Those products will simply be withdrawn. And I can tell you, I've talked with many companies,'cause I'm very much in the middle of this whole thing, uh, many companies are pretty certain they would be withdrawing products if in fact this happened. So what does that mean? We're gonna start off with a situation where there's a perceived safety risk, which is not true. There is no safety risk and we're gonna turn it into a real safety risk. Where now we have patients that can't get their medications in Europe Okay. And potentially elsewhere. Okay. Because even if it continues to be acceptable in other parts of the world, if you're a major global drug company and you have a. A smaller volume product and all of a sudden you take the European market out of the equation and that amount of sales, if you will, it may be that it's no longer viable economically for you to continue making that product, even for the other markets where you don't have to reformulate it because there's not enough, you know, volume to drive producing that product and having a plant dedicated to it, et cetera. So you could see people around the world lose access to products who, their government doesn't have any problem with TIO O two, but because of what Europe does, it could impact a lot of people globally. So that, that's really the key. When it comes to your question about impact, there's lots of technical implications, regulatory filing implications, but the real issue is patient access to drugs is gonna be limited. And then one last thing I'll mention, and then I'll shut up for a minute, ask another question, is the real question too is, Let's just think about that number again. 91,000 drug products. Okay? How many regulators is E M A going to have to hire to review 91,000 variation submissions? Okay. There, you know, there's been some estimates done that even if they doubled their workforce, it would probably take them 12 years to go through that many drug applications. Okay? So, and, and of course that's meaning that like all everybody's dedicated to doing these change evaluations. What's gonna happen to new drug development? You know, you know, all, all the new drugs. Does that mean some of them are now gonna get delayed? You could have people losing their life because they don't have access to new drugs, because instead people are looking at these variations and it's delaying the approval of the new drugs. All of these things are potential to. Impacts that this could have. So, you know, now you kind of can understand my earlier comments. This, this issue was huge and you know, if there, if there was an actual safety issue with TIO two that was credible, we all would be having a different conversation. We would all be saying, we gotta do whatever it takes. We gotta get it out of there. But that's not true when in fact there's no good science that really justifies this to even be having this discussion is to some degree ludicrous. When you think about the implications that we have in the pharmaceutical arena, which is obviously a lot more significant than in the food arena where, you know, if you lose a food product or you come up with a new and improved, it's a different color, it's a different product. I mean, that, that happens more routinely in, in the food industry, doesn't have the same implications of patients losing their lifesaving drugs.
Meg Sinclair:Absolutely. Yeah. Scary to think of the impact there with very little evidence behind it. Yep. Absolutely. So, switching gears back to, you know, the US and what's going on here in, um, California, my former home states, we hear about lawsuits and dolls that have been pros requesting the band of the same, um, titanium dioxide in just California, which honestly, California doesn't surprise me.
David R. Schoneker:Yep. Well, exactly. And, and again, this is, this is the effect of the media again. And, and, uh, you know, um, let's talk for a minute really about, uh, global, you know, what do global regulators think about this, right? We, we've talked about what's happened in Europe, what's happening in Europe, or just being discussed. Uh, a lot of times I get asked, well, you know, how does the f d a feel about that? How does, uh, how, how does other regulators in other countries feel about that? Well, the answer to that is the F d A has done their own thorough evaluation of this. And they don't have any safety concerns. And in fact, they have, uh, you know, provided public statements, uh, showing that they actually think that the whole approach that f c used was incorrect. Okay. Uh, so F D A in the US has no concerns about TIO two in terms of their evaluation. And they did do a very recent valuation of not only all the data that Efsa looked at, but all the new data that's been coming out as well. And they, right off the bat, I mentioned earlier how Efsa had looked at these nano grades that don't really have anything to do with T O two F D A. Looked at what they did there and said, well, no, that's not relevant, because that's not the material we're talking about. You can't look at data gaps on a material just because it's supposedly the same chemical, but it's not the grades that have anything to do with the material that you're using here and apply that.'cause it's, they're not, it's apples and oranges. Right. So, F D A made it clear that when they looked at the studies on the pigment grades of t TIO two, uh, and taken everything into consideration, they didn't have a concern. Uh, same thing in health in, in Canada. Okay. Uh, health Canada actually went one step further. Not only did they do a very thorough scientific evaluation of this, they published a large report, I forget how many pages it is, 50 to a hundred pages. It's, it's a big report. Um, uh, basically on the safety of TIO two. And after their assessment basically came down as saying, We don't see any concern with the safety of t o two and, uh, you know, much like F D A, uh, disagreed that looking at these nano grades should not be part of the consideration. And, you know, from a toxicology standpoint, it's kind of irrelevant ill information. Um, and so Health Canada also said we have no intent to take any action against TIO two in a published report that's out there on online, um, Australia, New Zealand, their regulatory agency called FSS a s uh, also did their own evaluation here. Same thing, published a report online. We've looked at all the details. We don't see any, uh, any issues. Um, and interestingly enough, in the uk. The Food Standards Authority, which after Brexit, you know, the UK is now on their own. Mm-hmm. Uh, they don't necessarily have to just go along with Europe all the time. Uh, they do their own evaluations, uh, and, uh, you know, the Food Standards Authority, uh, did their own evaluation after what FSA did. Uh, and came to a different conclusion as well. And they basically said, no, you know, we don't see a safety problem with TIO two. But they actually went one step further in the interim report that they published, they're gonna have a final report coming out next month, but they published an interim report and they actually were extremely critical of the entire approach that FSSA took. And basically said they felt that what FSA has done is unnecessarily. Concern the public over a situation that should have never, you know, been put out this way. It was rather interesting to see how critical they were in their report of ssa, which they used to be part of. But that kind of tells you, you know, nobody else in the major countries have a concern. And in Japan, uh, there's a new study that just came out recently. It's in the process of being published where they actually looked at even the nanoparticles that are smaller than the ones that Efsa was worried about. Uh, and, and that study was well designed, came out totally clean. And in Japan they also have said they don't have any concern they're going to, they're gonna go through a formal evaluation, but, uh, based on what they know right now, they don't see any concerns. So, major countries, no problems. There are a few countries that tend to be, uh, Following, uh, what Europe does, they don't really have a, a large set of toxicology experts on board, so they tend to go along with Europe, uh, et cetera. Uh, and so we've seen some of the Middle Eastern countries also put forward a ban. Um, basically when you look at what they've said, they said, well, we're doing it because Europe did it, right? Not because they found more science. Okay. Um, we've had some discussions through, uh, the U S D A Foreign Agriculture Service and the W T O with those countries. And actually some of those countries are now thinking of possibly holding off and pausing the ban. Okay. Uh, and, uh, that said, excuse me, down in South America and Visa, shortly after, uh, FSSA came out with their opinion, uh, and Visa, um, sort of had a knee jerk reaction saying, well, we, maybe we should do it too, like Europe's doing it. But we sent them a lot of information with some of these facts. Uh, and the, and what other regulators were saying, and they've now sort of gone quiet, so nothing's happening there yet. So the big thing is the joint expert Committee on food additives, which is the global group that assesses the safety of food additives. They're part of W H O and F A O, they have taken on to do a global safety evaluation of all this data. They are, they put out a call for data. Everybody sent'em all the information, including all this new information. They are currently doing that evaluation. They will have a meeting in September or October, I forget this year, where they're gonna be doing their own assessment, and then they will publish a JVA opinion, which will represent sort of the, the world class toxicologists from all over the world. So what we've tried to be telling a lot of these other countries is don't go and just ban it, because Europe did wait and see what JVA has to say. These are the world's best toxicologists. And then based on what they say, Make appropriate decisions. So, you know, a lot of countries seem to be in that mode now where they're gonna wait to hear from Jfa, which is exactly what they should do. That's why we have jva to make these kinds of decisions. So, so that's all in the process now. Now, getting back to your initial question about California, okay? Mm-hmm. That's another interesting situations, to say the least. And, and you said you lived in California before. Where, where did you live in California? I grew up outside la. Okay. Okay. Well, and as you know, California always tends to have, let's just say a little bit of a different view on things. Um, prop 65, you, you name it. It's always a Yes a little bit, you know, over the top on some of these things, um, uh, compared to some other states. Right? So what's happened, two things started, uh, there, there were, that got news media attention. Okay? There was a couple of lawsuits that came out last year. Uh, one against Skittles. Another on Tylenol that, you know, basically what the, uh, uh, the people filing a lawsuit said was, well, you know, Europe has banned this material and these companies that make these products don't have a warning label on their containers. It contains, and they called it this toxic material called titanium dioxide, and nobody has called it toxic material. And certainly even what SSA said, never alluded to that, but that's what these lawsuits said. And basically, um, they, you know, they were trying to sue these companies for, you know, putting their, their consumers at risk know they not having warning labels and stuff. Well, long story short, the Skittles lawsuit was thrown out pretty much the same thing for Tylenol, but it got a lot of media attention. Okay. Uh, and of course if you talk to the consumer on the street, you know, you, a lot of people come up to me, oh, they hear I'm involved in it. Oh, what about these Skittles? Right? What about, and it's like, I eat Skittles all the time. I will continue. There is no issue with Skittles, right? Uh, or any other of the food products of many, which, which contain TI two as well as the drugs. However, what's now happened is the NGOs who basically want to do away with all food additives, pretty much they, they don't like any of them. Um, they hooked onto this issue. And, uh, there's a particular assemblyman in the assem, the, the, the state assembly in California, uh, who, uh, you know, it, it was on a mission to get rid of some of these additives. Titanium dioxide is one of five additives that he has a concern about. And of course, when you dig into this bill, that heap has proposed. You'll find that there are several NGOs that are the ones that are, uh, uh, you know, doing, uh, uh, things around the country on this now, uh, who were trying to get rid of these additives, right? For, you know, no good scientific reason realistically, even though I think they think there is. Um, and, uh, unfortunately, this assemblyman in California put forth a bill to ban these five additives, of which TIO two is one of foods. Now, this is not a medicine thing, at least yet, um, uh, in foods. And unfortunately, he was very convincing. Uh, and he got the house to approve the bill, or not the house, the assembly. Okay? Now that Bill has moved to the Senate in California where there's gonna be hearings that start, I forget, it's either this week or next week. I. On this bill, and of course, we're all trying to provide them with a lot of the facts behind this and some of the things I've talked about with you today, um, uh, to hopefully convince the Senate not to go forward with this, okay? Uh, because, uh, you know, if you, if you look at this, this is a, this a whole different issue. Now, if California actually did ban this in foods, you would've one state in the country that doesn't allow all the food products that all the other states allow. Okay? How is that gonna work from a trade perspective? You know? Um, are companies really gonna reformulate products just for California? Okay. It's an important market, but, you know, um, so, so that's, uh, you know, sort of a strange situation. And if you really look at this, this is a total affront to f d a authority. On, uh, protecting the public and, and food safety regulation. Okay? The F D A has the federal authority to do these types of evaluations. And the F D A has basically said, we don't see a problem. Okay? And we did evaluate recently all the new data. The bill says the F D A hasn't looked at this since the sixties. Not true. They simply don't know that the F D A has looked at this, right? Um, but they passed it anyway in the assembly, right? So, um, you know, uh, you know, this, if this gets approved, it will be the first time that any state has actually banned something that F D A has said they don't have a problem with. And you can start thinking about the difficulties that, that may cause, especially in today's world. If certain states start saying, well, we can do whatever we wanna do, regardless of what the F D A says. And it, and, and, and, and of course these N G O groups that are behind this have taken the same bill and they started the similar bill. They found a congressman in New York and one in New Jersey to try to have, uh, the same sort of bill. Now those bills haven't really moved at all yet, like the California one is and hopefully won't'cause they're not based on any kind of good science. Um, but you could start to see where you could have this patchwork of regulation that would be, from an industry perspective, impossible to support. And like I said, it's a direct challenge to f d A authority, which could start to affect, you know, drug approvals and, uh, all kinds of other things. If F D A is no longer the authority that everybody goes to for these kinds of decisions. So it's got a lot of other hidden implications that, um, uh, are not just this one case.
Meg Sinclair:Yeah. What can industry do to fight these non-scientific precautionary bans across states and countries and try to continue the use of titanium dioxide, which really seems important to our drug and product, drug product quality, and our food industry?
David R. Schoneker:Yeah, no, I, I, i that it's a difficult situation, I'll be honest with you.'cause when you get, when you get this media, this negative media attention that the, that, that the NGOs have been able to stimulate here, even in the us Uh, uh, and certainly it's what happened in Europe before the science started to, you know, kicked in, if you will. Um, uh, you know, all you can try to do is educate, try to bring the real science forward, run additional studies that in fact may answer any uncertainty questions that are out there. But the difficulty we have is that once it gets out into the media and into some of this arena, science no longer matters. Truth and facts no longer matter as we've seen with many things. Right? Um, and that makes it very difficult to get the messaging to the consumer who ultimately is believing what they're hearing sometimes. And so, um, but that said, um, you know, there are many efforts to do exactly what I just talked about, right? The industry, uh, has put together a major new science program, uh, to, uh, run, you know, again, millions of dollars of new studies. Uh, To answer any possible uncertainty that anybody still has and all the things that have been brought up. Those studies are underway. We've got various industry groups, which I'm involved with, almost all of them, uh, uh, you know, that have formed different coalitions and, uh, you know, joint, uh, association groups, et cetera, where we're sharing information and we're trying to utilize this to make sure we're bringing all the facts forward to the regulators around the world who are making decisions on this, and try to start figuring out what kind of messaging can we put together in a way that can get to consumers as well. Uh, we've been having conferences. I just coordinated a big conference in Washington, DC last week where world class toxicologists all came in to talk about the real safety situation, uh, and the impacts this would have if we went to pharma. And we have a, we're putting together a whole white paper coming out of that conference to try to, again, bring these facts forward to E M A. So they're aware of the reality of what a ban would mean so that they think about that before they make a decision. Uh, so there's many things in the works, uh, you know, to try to affect the outcome and hopefully not see, you know, this impact pharmaceuticals anywhere, including Europe. Uh, it may, it may be too late to sort of save the food situation in Europe, uh, because it's, uh, politically be difficult for them to go back on this at this point. But certainly what we're trying to do is also influence with facts and science regulators in the rest of the world, not just to blindly follow Europe, but to in fact, see what Jfa says based on good science and world-class experts, and use that information to base their decisions on.
Meg Sinclair:As you're involved on the front lines on this issue, do you have any final thoughts on the titanium dioxide situation?
David R. Schoneker:Yeah, uh uh. What I would say to sort of finish off the discussion is here, unfortunately, I wish it was just a titanium dioxide situation, but actually this is the tip of the iceberg, okay? Because what's happened now is many materials that are common food additives and pharmaceutical excipients contain a certain portion of nano pardons. France, as I mentioned earlier, is worried, overly worried, in my opinion about nanoparticles. Okay? They have put together a list of 37. Food additives, and many of them also are form major pharmaceutical excipients, okay. That are known to contain or thought to contain nanoparticles at some level. And they want all of those materials to go through the same evaluation by FSSA in the same way that SSA did it, using the same approach that they used. Uh, looking at this nano, uh, part, uh, you know, concern. Um, and that, and that's, that's on the horizon. So what happens with titanium dioxide is going to set a precedent that could potentially impact many of the most important excipients that we have in the pharmaceutical industry and also in the food industry, uh, for similar reasons. Okay. Uh, and just to give you an example of what I'm talking about, I. Remember those alternatives that I talked about that people are looking at to try to use and place a tio, O two, calcium carbonate, iron oxides, try calcium phosphate, iso malt. Guess what? All of those are on the French list of 37. Okay? Oh, no. So all of those, in fact, iron oxide is already under evaluation. And I can tell you iron oxide does contain nanoparticles. There are no real, you know, safety issues that have ever been documented with it. But there are, you know, some of the, you know, when you start looking at these nano things that, uh, people worry about that, uh, go beyond science, sometimes, uh, some of the same concepts might come up in some people's minds. And so, you know, these materials are gonna get looked at by fsa and if the same approach is used, there's certainly the possibility that some of those materials could through the same kind of situation. Think about the implications. If the industry actually did reformulate thousands of products and millions or billions of dollars and regulators, you know, spend all this time to substitute or try to utilize, uh, you know, calcium carbonate alternative, even though they're gonna have a, what I'll call a second class product at the end. Okay. If they do all of that, only to find that two or three years later, calcium carbonate or iron oxide, so I'm talking about, or one of the alternatives that they've now used is got the same problem. Now think about what the implications that would have. Right? And, uh, again, like I said earlier, if there actually was a safety problem that's been demonstrated, we'd all be having a different discussion. That's simply not the case here. Uh, much to the NGO's chagrin, there's just no science backing up their arguments on this. Um, so, you know, I, I talk about like these. Pigment type materials that are used as alternatives to TIO two. But let me just throw out a couple other excipients that people who might be listening to this might think, you know, somewhat important to pharmaceuticals. Hmm. Microcrystalline cellulose happens to have nanoparticles and is on the French list. Magnesium steroid. Oh, on the French list. Mannitol on the French list. I could go on. Okay. Hmm. Microcrystalline, cellulose and magnesium steroid. Probably the most used fillers and lubricants in the entire pharmaceutical industry. Think of what would happen if the same thing happened to them. Right. So again, this, this is something where we need to find a way. We need to pull out the stops. Everybody in the industry needs to get together, advocate, do studies, do whatever we have to do, lobby, et cetera, to make sure that science somehow prevails. As opposed to this, uh, overly precautionary thinking that is based on the precautionary principle, which is commonly used in Europe, especially in France. Um, uh, uh, when we look at this, otherwise, we're gonna have problems that go way beyond what we're talking about today. And this again, could be, like I said, the tip of the iceberg. Um, and so we've gotta, we've gotta find a way to nip this in the butt and get science to win. Uh, and not just media and politics dictating where all this ends up going.'cause ultimately, at the end of the day, this will be my last comment, patients are at risk here. Patient safety and availability of life-saving drugs is, is the, is is what, uh, you know, this is really all about. And patients will suffer if there were to be a ban. People might think taking this nasty stuff out of the drugs is gonna somehow benefit them. There will be no benefit even if you do reformulate because there's no risk in the first place. Um, however, there'd be a significant risk if you can't get your drugs or you can't afford them, or if you can't afford them. And, you know, we talked about availability here, but you're right, the cost issue. Think of, uh, you know, if it does cost you one to one and a half million dollars to reformulate, who do you think is gonna pay for that? Do you think that SS are just gonna absorb all that? No, you know, drug, drug prices will go up and, and that is, that, that's anti what everybody wants, including the government. Right. Um, that needs to be thought about, you know? Yeah. We hear, we see all the pressure here in the US as well about lowering drug costs. You know, what would happen? This is counter to that. Yeah, exactly. And, and if you think about even the, the politicians who sort of drove some of this in Europe in terms of the ban, okay. They probably thought this is what would get them. Votes with the voters because, oh, we're keeping this nasty stuff out of your food products. Okay. Um, that's a kind of short-term thinking, I think, because if, if you're that politician and all of a sudden it comes out in the media that your decision on this is now the reason that all of your, your voters can no longer get their drugs, I have a feeling that what they thought was a good idea is not gonna get them elected in the long term. You know, because, you know, not having access to these drugs, which will happen, by the way. Okay. I mean, the one thing I can say that I can absolutely say I'm certain of is 91,000 drug products will not be all reformulated. That is simply not going to happen. It's not even possible for that to happen. So if that's true, what does that mean? There will be drug shortages. Probably on many drugs more than there are today. And that's one of the biggest problems you hear about these days. Talk to a doctor, you know, and, and I, and I plan to talk to doctors and nurses and others about this. What do you think about this? You know, how would you like this to have this effect? We need to get them on board and, and we plan to.
Meg Sinclair:That's great. And so normally we wrap this podcast with a question about where we would find you in a bookstore, but as we're both skiers, I thought I would ask, what slopes would I be most likely to find you on this next ski season? Hmm.
David R. Schoneker:Good question. Good question. Well, I'm actually running a big trip for the Eastern Pennsylvania Ski Council to Val Gardena, Italy in the Dolomites, um, in, uh, in the beginning of March, this coming sea season. So I'd love to see, uh, in the Dolomites, that's, uh, certainly one place I'll be. And then the other, uh, big trip I have, uh, uh, that I'm, uh, assistant trip leader on is a big trip, uh, for our council to go to, uh, uh, heavenly out in Lake Tahoe. So I'll be going out to California as well. Uh, and, and hopefully I'll be able to have, you know, my, uh, my food with Tia two in it when I get there. Uh, but, uh, so you know, I'll be, uh, skiing in beautiful Lake Tahoe as well. How about yourself? Do you have something planned? I ski here
Meg Sinclair:locally in Colorado. Oh, I heard, I forgot. I've not done Steamboat Springs. That's, uh, on my list here to one of my last ones I haven't done here in Colorado. Oh, you haven't
David R. Schoneker:done Steamboat yet? I haven't done Steamboat yet. You, you, you've gotta do that actually in 2025 we'll be running a trip to Steamboat, so, um, maybe run tea out there then. Yeah.
Meg Sinclair:And we can catch up on, on the latest on titanium dioxide
David R. Schoneker:then. Absolutely. And, and hopefully we'll have more positive news to talk about at that point.
Meg Sinclair:Yes. Well, it's been enlightening conversation today, Dave. I really appreciate you joining us today on the podcast. Um,
David R. Schoneker:well, thanks a lot for the opportunity to, to talk to you about this topic. As you can tell, I'm, uh, I'm a little bit passionate about it because I've, uh, I've seen what the, the downside of this could be and, uh, um, it's a serious issue that unfortunately not everybody in the pharmaceutical industry really understands what's going on yet and, and the implications it could have. So we we're trying to get everybody. Fired up on this issue to understand the facts and, and everybody get together and get aligned on how we can, uh, make sure this goes down the right pathway. Great. If our
Meg Sinclair:listeners want to learn more or get involved, where can they go to learn more about you and Black Diamond Consulting and how to get involved in titanium dioxide?
David R. Schoneker:Well, the easiest thing to do would be to go to my website, which is, uh, uh, uh, htpp s slash like normal, and then just black diamond regulatory.com. Great. We'll post
that
Meg Sinclair:in the show notes. Thanks so much for joining us today, Dave. Great.
David R. Schoneker:Well, thank you very much for the opportunity, and again, uh, for those of you who were listening to this, uh, hopefully this was, uh, educational to you and brought some, uh, things to light that maybe you didn't fully understand. And if you do, um, want more information, please let me know. I'd be glad to, to help you with that.