0:18

hi everyone, and welcome to From Lab to Launch

0:20

by Qualio I'm Meg, your host.

0:22

Thanks for tuning in today. Before we

0:24

jump in, we'd love it if you rated the podcast

0:26

and shared it with any of your science nerd friends.

0:29

We know you have some. If you'd like

0:31

to be on the show, please fill out the application

0:33

link in the show notes. We're grateful

0:35

for all the interest we've had lately. Today

0:38

our guest is David Schoneker, who is

0:40

currently the president of Black Diamond

0:43

Regulatory Consulting, a consulting

0:45

firm specializing in providing regulatory

0:47

and quality consulting for the pharmaceutical,

0:50

dietary supplement, food, and related

0:53

industries. The firm provides

0:55

expert advice for difficult problems

0:57

and training on excipient and food

0:59

additive regulatory quality

1:01

and supply chain concerns. With

1:04

over 45 years of experience working

1:06

in these areas, Dave has developed

1:08

strong networks with trade associations,

1:10

regulatory agencies, and

1:12

pharmacopedia around the world.

1:15

He is also an adjunct professor

1:17

at Temple University School of Pharmacy

1:20

in their RA/QA Master's program,

1:22

teaching courses in global excipient

1:24

regulations and the regulation of dietary

1:26

supplements. Prior to this, Dave

1:28

was the Global regulatory Director

1:30

of Strategic Relationships at Keller

1:33

County Inc. Without

1:35

further ado, let's bring David.

1:38

Welcome, Dave. How you doing, Meg?

1:40

Great. So to get us started, Dave,

1:42

can you tell us about the start of Black Diamond regulatory

1:45

consulting?

1:46

Sure. You know it, uh, I'm a,

1:48

I'm a, I'm a big time skier and,

1:50

uh, have a love of skiing all my life.

1:53

And, uh, when I, uh, retired from

1:55

Colorcon and, uh, started, uh, started

1:57

consulting, I was trying to figure out the name of my,

1:59

uh, firm and, uh, uh, my

2:02

daughter sort of, uh, gave me the idea

2:04

of, uh, working something with my love

2:06

of skiing into the name of the company. So

2:08

anybody who's a skier understands, uh,

2:11

what double black diamonds mean. And,

2:13

uh, obviously, uh, I have a firm out

2:15

of expertise in these areas, um, that

2:17

I like to, uh, be able to help, uh,

2:19

you know, clients with very difficult problems

2:21

that they have, uh, including the one that we're talking

2:24

about today.

2:26

That's great for our non-skiers. Do you wanna

2:28

tell them what black,

2:29

black diamonds mean? Good, good, good point.

2:32

Yeah. Yeah. You know, black diamonds stand for

2:34

expert trails, uh, double

2:36

black diamonds, uh, which is my logo,

2:38

essentially. Uh, stand for,

2:41

you know, uh, you know, sort of super

2:43

expert trails. Uh, some of the most difficult

2:45

on the mountain.

2:47

Very good. Um, so

2:50

one of the things we keep hearing about in the news

2:52

and, um, our concerns around titanium

2:54

dioxide, um, in the news,

2:56

can you tell us a little bit about what titanium

2:58

oxide is and how it's used in the

3:00

food and pharmaceutical

3:01

applications? Uh, absolutely.

3:03

Yeah. Titanium dioxide, uh, outside

3:06

of water. Is probably

3:08

the most used, uh, excipient

3:11

in pharmaceutical formulations. Uh,

3:14

it's also, uh, a big time ingredient

3:16

in many food applications as well.

3:18

Um, it is a pigment, it

3:21

is a white pigment, uh, and it's

3:23

got some very unique properties. Uh, That

3:25

really no other material that

3:27

you can utilize in pharmaceuticals,

3:30

um, uh, have the kind of properties

3:32

that Tio two has, and we will talk about

3:35

those as we go forward a little bit. But

3:37

it, it, it tends to be used as, uh, not

3:39

only a white colorant and white pigment,

3:42

but in opacifier. So

3:44

that even if you have, uh, different

3:46

colors on a coating, let's say on a,

3:48

on a tablet, uh, or in a capsule,

3:50

you need to opacify that color

3:52

and so, you know, to, to make it bright

3:54

and also make it, uh, so that light

3:57

doesn't just, uh, trans, uh, so it's

3:59

not transparent, if you will. Um, and

4:01

that provides, uh, protection to pharmaceuticals

4:04

in, in terms of light stability controls,

4:07

et cetera. So, you know, Tio O two

4:09

is one of the, uh, you

4:11

know, what a lot of people tend to refer to is sort of

4:13

one of the perfect excipients that

4:15

have many different uses, not

4:17

only for coloring and opacification

4:20

in pharmaceutical products and

4:22

food products as well. But

4:24

also to really protect the

4:26

a p i. So many APIs

4:28

are light sensitive, uh, and

4:31

Tio O two is one of the main ways

4:33

that you can protect, uh, the light sensitivity

4:35

of the a p I. So it, it provides a lot

4:37

of stability to drug products

4:40

and because of that, it's been used extensively

4:42

in literally thousands

4:44

of drug products all over

4:46

the world and many, many food products

4:49

and dietary supplement products as well. Are

4:52

there similar ingredients that can

4:54

provide the same type of properties as titanium

4:56

dioxide? I. Nope, there

5:00

is nothing that you can use

5:02

in pharmaceuticals that comes anywhere close

5:04

to the properties that you have with tio two.

5:07

There are some materials that can be used

5:10

as alternatives, um,

5:12

in some cases, but they're by

5:14

no means, uh, substitutes for t

5:17

o two, and they don't come close in terms

5:19

of the opacification, uh,

5:21

or light protection that they can provide.

5:23

So the answer is really there, there aren't

5:25

any real alternatives that are viable

5:29

in all applications. In some

5:31

cases, there might be materials

5:33

that would provide something that I

5:35

would call good enough, but

5:37

certainly not the best in terms

5:39

of their properties and the way they're used. Okay.

5:43

So this has really been the gold

5:44

standard thus far. Absolutely. And

5:46

that's why it's been used, um, all over

5:48

the world in, you know,

5:50

almost anything that, you

5:52

know, has any kind of color in it. Uh,

5:55

you know, whether it's white colored, you name

5:57

it, um, uh, you know,

5:59

uh, if it's coated, if it's a,

6:01

a capsule, any of that has

6:04

T two and it, uh, historically,

6:06

um, you know, it's been in most

6:09

products on the market. Interesting.

6:12

So there's been a lot of news coming out of Europe. Can

6:14

you explain what has happened there recently

6:16

with, um, titanium dioxide

6:19

in

6:19

foods? A a Absolutely.

6:21

Yeah. There, there, there's, there's a lot of press

6:23

that people hear about and they only get one side

6:25

of the story. And, and unfortunately, you

6:28

know, uh, for, uh, you know, the consumer

6:30

out there who's not a, a toxicologist

6:33

or a scientist, they don't always understand, you

6:35

know, some of the details. But you know, what

6:37

has happened, really, uh, it, as

6:39

far as I'm concerned, uh, it, it's, it's

6:41

sort of a travesty what's happened in Europe. Okay.

6:44

Uh, i, is that, you know, um,

6:47

the European, uh, uh, food Safety

6:50

Authority was charged with reevaluating

6:52

the safety of many different food and and

6:54

color additives. Uh, and

6:57

back in 2016, they

6:59

started a reassessment of titanium

7:01

oxide, and they looked at all the,

7:03

you know, newer studies that were out there,

7:05

et cetera. Um, and

7:07

their initial evaluation was, I. We

7:10

don't see any problems with titanium dioxide.

7:12

However, there's a few data gaps that,

7:14

uh, we feel we'd like to fill. So they put out

7:16

a call for data to the industry.

7:19

Uh, the industry responded, spent

7:21

millions of dollars on new studies

7:24

to fill the gaps that that

7:26

sso, which is the abbreviation for,

7:28

uh, the European Food Standards Authority,

7:31

um, that FSSA requested, did

7:33

every study they, they asked for. Okay.

7:35

And, uh, you know, supplied

7:38

that data as it was coming together. Uh,

7:40

FSA looked at this and reassessed

7:43

it several times. Um,

7:45

and during that process there

7:48

was a study that was funded by the

7:50

French government in France, um,

7:52

that, um, uh,

7:55

had a very poor study. Design

7:57

should have never been considered as.

8:00

Uh, having any credible data, as far as

8:02

I'm concerned. And, and, and as you'll hear, many

8:04

toxicologists all around the world. Um,

8:07

but unfortunately, uh, in France,

8:10

uh, there's, uh, you know, I'll

8:12

call it in, uh, over precautionary

8:15

concern about the presence of nanoparticles.

8:18

And, uh, in, in many

8:20

materials and, and in titanium dioxide,

8:22

there is a certain portion of, uh,

8:25

the pigment that is nanoparticles.

8:27

That's actually what gives it, its

8:29

unique properties. Without that, it

8:31

wouldn't have the properties, right? So

8:33

the other thing is those particles have

8:35

always been present in the t o

8:37

two, that every person on the planet has

8:40

been eating at significant

8:42

levels or taking in drugs pretty

8:44

much every day of their lives for

8:46

the last a hundred years without even

8:49

one person ever

8:51

having an adverse effect. It's ever been tagged

8:54

to titanium dioxide, however,

8:57

This very poorly designed study in,

8:59

in France, um, indicated

9:02

some potential concerns, and I won't go into

9:04

the details here for this audience, but, uh,

9:07

they, they indicated some potential concerns,

9:09

uh, which got a lot of media attention and

9:12

a lot of political attention, especially in France

9:14

because they're worried about

9:17

nanoparticles. Okay? Um,

9:20

so what happened was, uh,

9:22

France believed there was a problem.

9:25

Now remember, the French government funded the

9:27

study also, so that's important to

9:29

to stress. They funded a study and they

9:31

had a poorly designed study that got a certain

9:33

result on something that they were nervous

9:36

about. Okay? Uh, so. Um,

9:39

France basically wanted to

9:41

ban the material based on

9:43

this question that came up. Uh,

9:46

they went to ssa who was reviewing

9:49

all of this data during this reassessment.

9:52

And even ssa, the European Food

9:54

Safety Authority, looked at the data from France

9:56

and said, there is nothing here that we believe

9:59

should change our position that

10:01

t o two is safe. Uh,

10:03

and in fact, we're gonna continue its use and

10:06

maybe ask for a few additional studies

10:08

to fill some data gaps. Okay.

10:11

Um, which industry did

10:14

okay FSA continue

10:16

to say it was safe and they

10:18

continued to say it's safe after multiple

10:20

times that France asked them to reassess

10:23

the data and new data, et. Uh,

10:27

uh, you know, right towards the end when

10:30

everybody in industry was expecting

10:33

that FSA had completed their evaluation,

10:35

that they were going to provide a acceptable

10:38

daily intake for this material, which was what

10:40

their goal was, they changed

10:42

course at the last minute and

10:44

basically said, well, we've now looked at all these

10:46

studies on truly

10:48

nano grades of t i o two that

10:51

actually have nothing to do with the pigment

10:53

grades that we use in foods and pharmaceuticals.

10:55

They're designed for catalyst use in the chemical

10:57

industry. But, but they looked at

11:00

that material and they said, oh, there's more data

11:02

gaps now. And because we

11:05

now have questions, we can

11:07

no longer say Tio O two is safe.

11:10

Okay? Now again, those, that wording's

11:12

important saying that we have

11:14

data gaps and we can no longer say

11:16

it's safe is not saying

11:19

there's a safety problem. Okay.

11:21

Yes. It's simply saying we have some

11:23

uncertainty and some questions. Now,

11:25

what they should have done is what they did back

11:28

in 2016 or 17,

11:30

when they asked the industry for more data

11:32

to fill the data gaps. They didn't

11:34

do that. They published their opinion

11:36

and said, we can no longer say it's safe

11:39

because there's data gaps. Well,

11:41

the politicians in Europe took

11:44

that to mean there's a safety problem. We

11:46

have to ban this material. And

11:48

very quickly moved towards

11:51

banning the material. Uh, so

11:54

this started in France. It

11:56

became political. And

11:59

what I would say the term that I tend to use

12:01

in a lot of my presentations on this is,

12:04

uh, uh, political toxicology

12:07

got into the mix. Okay?

12:09

And this really doesn't have anything to

12:11

do with good science and

12:13

a real safety problem. It

12:16

has to do with. What happens

12:19

when negative media comes out that's

12:21

not based on good science and

12:23

it gets beyond the science.

12:25

Okay. And so ultimately, after all

12:28

of this, and I know I've gone through a extensive discussion

12:30

here, but it's important 'cause it sets up the rest of our

12:32

conversation. Um, essentially

12:35

Europe decided to ban, uh,

12:37

uh, titanium dioxide for food

12:39

uses because that's what they

12:41

were evaluating it for. Okay.

12:44

Um, and that ban went into

12:46

effect, uh, in, uh,

12:48

2021, uh,

12:51

for all food products that

12:53

could no longer be made with titanium

12:56

dioxide in, in the European market.

12:59

And that required companies to have

13:01

to do massive reformulations of

13:03

many, many different food products. Um,

13:06

and in many cases, um, the

13:08

products that, uh, used alternatives,

13:11

uh, maybe were, again, I'll call it good

13:13

enough. But not necessarily

13:16

as good as what they could be with titanium

13:18

dioxide. Now, the food industry is a lot different

13:21

than the drug industry, but I wanted to answer your

13:23

question about foods and what happened in Europe so

13:25

far. Are

13:27

there any really

13:29

good studies that address

13:31

or identify safety concerns with the use

13:33

of titanium dioxide in foods

13:36

and drugs? Is there anything on,

13:37

on? Well, that's, that's a really good question. And,

13:40

and, and when you look at it, there are,

13:42

you know, especially since this happened, obviously

13:45

more studies were done both

13:47

by the industry, by, uh, people

13:49

who, you know, the NGOs and, and other

13:51

groups that are now fired up

13:54

against this material, et cetera. And

13:56

you'll find that there are some studies out

13:58

there that, you know, claim. There's

14:00

some issues, but we've looked at

14:03

these in detail and essentially

14:05

there is no good design study

14:08

that has any scientifically credible information

14:11

that actually shows a real

14:13

safety concern. Uh, there

14:15

are many new studies that the industry

14:17

has funded, uh, to answer

14:20

those uncertainties and those questions that

14:22

came up. And those studies are underway.

14:25

Uh, and some of 'em have been completed. And

14:27

of course, you know, they show what

14:29

we expected, that there's no problem.

14:32

Now, there's some still going on, but there was

14:34

a specific study that was done,

14:36

uh, at, uh, university

14:38

of Nebraska and Michigan State

14:40

University ran a major study.

14:43

Basically the study in France that

14:45

started all this was the, the, the

14:47

author's name was Batini. So we call it

14:49

the Batini study, okay? Mm-hmm. Uh,

14:52

so what, what, uh, Nebraska

14:54

and Michigan attempted to do was

14:56

to try to see could they replicate, What

14:59

happened in that study to see whether or not actually

15:02

there was an issue or not.

15:04

Okay. Which is, you know, what you do with good science,

15:06

you try to make sure that, uh, you know,

15:09

that you can replicate these things. They,

15:11

they put together an extremely well

15:14

designed study to try to answer

15:16

all the questions about that Batini study

15:19

as to whether, you know, we should trust

15:21

it or not. Right? And

15:23

I'm happy to say after Nebraskan,

15:26

Michigan finished their study, it

15:28

came out totally clean, not

15:30

validating any of the results that

15:32

Batini had or any of the question marks that

15:35

Tini had brought up in his paper

15:37

or their paper I should say. And, uh, so,

15:40

you know, that's just one study that that

15:42

is out there and that's published and there's been

15:44

several others done and they all keep

15:46

coming up clean. Now, this is not

15:48

a surprise. Like I said, this material

15:50

has been ingested by probably

15:53

every human on the face of this earth

15:55

for their entire lifetime. Um,

15:58

With no effects that

16:00

anybody's ever actually seen. So,

16:03

you know, short answer to your question,

16:06

no, there's no credible science that

16:08

justifies that there's actually

16:11

any safety problem with TIO two.

16:13

Now, unfortunately, because of the

16:15

way the media has gotten out on this, a lot of people

16:18

don't believe that. Um, you

16:20

know, there's a lot of, uh, it, it, I'll use

16:22

today's, uh, vernacular here. There's

16:25

a lot of fake news out there about TIO

16:27

two, but at the end of the day, there

16:29

is no real safety problem with this material

16:32

that's been demonstrated. And there are

16:34

continuing ongoing studies to

16:36

continue to reassess that.

16:38

Reevaluate and verify

16:41

that that's true.

16:44

So thinking of the food ban in Europe,

16:46

does that have any impact on dietary

16:49

supplements?

16:50

Yes, it does. Um, pretty much all

16:52

dietary supplements in Europe are

16:55

considered food products, so this

16:57

automatically had an impact on

16:59

all dietary supplement products that

17:02

are marketed in Europe. Uh,

17:04

and, um, uh, uh, again,

17:06

a lot of people had, well they had to do one of

17:08

two things. They had to either try to reformulate

17:11

to something as best as they could

17:13

with the alternatives, but

17:15

that doesn't always work. Okay. And

17:17

in other cases, products were withdrawn

17:20

and essentially no longer marketed

17:22

in Europe. Still can be marketed at most

17:25

other places in the world. But, um,

17:28

you know, they lost access to some of those products

17:30

because there was no economics that would drive

17:32

that kind of reformulation effort, uh,

17:35

for certain types of products. Um,

17:37

so there, there's already been an impact in

17:39

Europe on dietary supplements.

17:42

And we expect to see further impact on pharmaceuticals

17:45

next

17:46

in, well, that's, that's, that's the, that's the big

17:48

hinging, uh, question right now. Because

17:50

what happened was when

17:53

this ban, uh, was put

17:55

in place in, in Europe, it was put in place

17:57

specifically for foods. But

17:59

the question got brought up by the politicians

18:02

and the NGOs. Okay. Uh,

18:04

hey, this stuff is used in medicines too.

18:06

We should ban it there as well. Uh,

18:09

and fortunately, uh,

18:11

the European Medicines Agency,

18:14

uh, you know, uh, realized

18:17

the impact this would have on pharmaceuticals,

18:19

which we, we'll talk about is, is

18:21

huge. Okay. And

18:24

they, and they gathered information

18:26

from industry and from other sources

18:29

and, and basically went to the European

18:31

Commission before this decision

18:33

was made and said, look, you know,

18:35

there, there is lots of information

18:38

showing that this would create a, a, you know,

18:40

a lot of. A lot of issues for pharmaceuticals.

18:42

We don't know if it's even possible what

18:45

the impact would be, what the potential implications

18:47

to drug shortages and everything

18:50

else would be. Um, and so they,

18:52

they basically asked for a delay

18:54

to allow for further evaluation.

18:58

So what happened was when the European Commission

19:00

banned TIO two for

19:02

foods, they basically gave

19:04

a three-year extension, uh,

19:07

for pharmaceutical use of TIO two

19:10

to allow the e m a to

19:12

gather further information from the industry

19:14

and their own sources, uh,

19:17

as to what the impact would be to try

19:19

to extend this, uh, band to

19:21

try titanium dioxide and

19:23

whether it was feasible or not feasible,

19:25

et cetera. They, uh, however,

19:28

basically said during that time period, they

19:30

encouraged the industry. To,

19:32

you know, look for alternatives, try

19:34

to use the alternatives, try to move away

19:36

from Tio O two. Again, all this is based

19:39

on the fact that there's really no safety issue,

19:41

but they were encouraging this because of

19:43

this belief. Uh, uh,

19:45

you know, again, remember this became very

19:48

political, not based on science

19:50

at, at, at several points. And,

19:53

um, uh, essentially

19:55

we're encouraging industry to do everything they

19:57

can. Okay? So we're

19:59

in that time period right now, and

20:02

we're, essentially what will happen

20:04

is the, uh, European Medicines

20:07

Agency is currently gathering

20:09

information industry and

20:11

others are supplying a lot

20:13

of, uh, answers to questions that they have

20:15

and supplying information about, you

20:18

know, uh, you know, what, what really,

20:20

uh, are the issues with trying to use alternatives?

20:23

Are they even possible in some of these applications?

20:25

And then ultimately, what

20:27

would be the impact on the drug supply if

20:29

somebody tried to go forward? With,

20:32

um, with a ban, uh,

20:34

in Europe on this. And, um,

20:37

so that the timing on that is

20:39

that the, uh, European Medicines,

20:41

uh, agency, uh, must

20:43

supply a report to the European Commission,

20:46

uh, by April of 2024,

20:49

uh, with a recommendation as to whether

20:51

or not they feel that the, the ban

20:53

should be extended to pharmaceuticals, uh,

20:56

or not. Alright.

20:59

That's less than a year away, so that'll be interesting

21:01

to see what happens there. Oh, yeah. As

21:03

far as alternatives, what I know we

21:05

said not much exists. Is there anything

21:08

that they can use? Um, As

21:10

an alternative in drug formulations, or

21:12

do they need to think about changing packaging

21:15

for safety? Well, good question, and,

21:17

and you know, uh, like I said, there are

21:19

some alternatives that people have been exploring.

21:21

A lot of work is going on in this area, you

21:24

know, to try to find something in case

21:26

a ban would happen. Uh, and,

21:29

uh, you know, probably when you look at the alternatives,

21:32

uh, probably one of the best alternatives,

21:35

and it's not good, don't get me wrong, but one

21:37

of the best alternatives, uh,

21:39

are things like calcium carbonate. Okay.

21:42

Uh, and, um, in some applications

21:45

where you're, you're, you're gonna have a, a

21:47

color involved, iron oxides

21:49

can sometimes, uh, be utilized.

21:52

There are some other materials, certain types

21:54

of rice starches, uh,

21:57

something called is molt, some tri

21:59

calcium phosphates. These are all materials

22:01

that people have been trying to use or

22:03

use in combination to

22:06

try to simulate the properties

22:08

of two. To the best

22:10

degree possible. Now, that said, just

22:12

to give you an idea of the difference, uh,

22:15

I said calcium carbonate probably

22:17

has the best opacification

22:19

properties, uh, next

22:21

to Tio o two of the things that are available

22:24

now, again, we're only talking about ingredients that

22:26

are approved for use in foods and drugs,

22:28

not, you know, pigments used in the pain

22:30

industry or, you know. Mm-hmm. Whatever. Mm-hmm. Um,

22:33

but um, to give you just an idea, there's

22:35

something we call contrast ratio, right?

22:37

Which really tells you sort of how opaque

22:40

something is. Uh, and,

22:42

and if you look at titanium dioxide, uh,

22:44

and the way we measure this is you make up a, a coating

22:47

and you, you make a, a sort of a

22:49

draw down on a, uh, a card

22:51

that's white on the top and black on the bottom.

22:53

And then you look for what the differences

22:56

are, where you see the break, you know, how

22:58

opaque do you see that black under there or not.

23:00

And there's a way of measuring that with a spectrophotometer,

23:03

and you determine that what's called this contrast

23:05

ratio and that, and so

23:08

a titanium dioxide has

23:10

a 90% contrast

23:12

ratio, which means it's almost

23:14

totally opaque, okay? Mm-hmm.

23:17

Calcium carbonate. Next best

23:19

thing 12.

23:22

Okay. Wow. So like, so you're,

23:24

you're talking like, you know, like 10 times less,

23:26

nine or 10 times less. Mm-hmm. Uh,

23:29

in terms of opacity. So you

23:31

can start to see where. If

23:33

you're gonna try to use that as an alternative,

23:36

uh, you know, you're not gonna have any of

23:38

that, uh, same kind of opacification.

23:41

So, so to give you an idea of what

23:43

that actually means in practice

23:45

is if you're using, let's

23:47

say you're making a, a pharmaceutical tablet,

23:50

and, you know, most tablets these days have coatings

23:53

on 'em with colors or white or whatever.

23:56

Almost all of them. Half titanium

23:58

dioxide, unless they've been developed very recently

24:01

with somebody trying these alternatives. Okay?

24:03

Uh, and so a, a

24:05

typical weight gain of

24:08

the film coating on a tablet,

24:10

uh, would be what's called a, you know,

24:12

a 3% weight gain, right? So, and

24:15

with a titanium dioxide. Coating

24:18

you can get by with only adding a 3%

24:20

weight gain and it gives you total opacification

24:23

to anything that's underneath. And why is

24:25

that important? Many tablets are

24:28

colored or have speckles

24:30

or you know, whatever. Like if you break a tablet

24:32

open, it's not always white. Sometimes

24:35

it's right if it's, if it's white, those are

24:37

the cases where maybe the alternatives might

24:39

work because you don't need as much

24:41

opacity. But a lot of tablets might

24:43

be yellow or brown or speckled.

24:45

Uh, think of a vitamin tablet. You know,

24:47

many times they're very speckled, et cetera. Uh,

24:50

and so you have to hide that. You have to

24:52

have opacification so you don't

24:54

see the color, but also you're providing appropriate

24:57

opacity to give light protection

24:59

to that a p i, which is the most important

25:02

part of this, right? If you

25:04

get away, and most people do with a 3%

25:06

weight gain of a typical Titan, a

25:09

titanium dioxide coating, if

25:11

you have a calcium carbonate, uh,

25:14

coating, some of the best ones that have been developed

25:17

to date by some of the best companies,

25:19

um, you're probably talking

25:22

anywhere from an eight to 10%

25:25

weight gain you're gonna have to put on

25:27

to even get close to

25:29

what you had with titanium oxide. It's

25:32

still not gonna be as good, but

25:34

you might, depending on the, the,

25:37

the, the surface of the tablet, you may

25:39

get by. Okay? Now think of that.

25:41

You get by now with 3% weight gain

25:44

of the coating, and now you're talking, let's

25:46

say eight to 10%, like three

25:48

times the amount of the coating has

25:50

to be added. Okay? That

25:52

means it takes you three times as long

25:54

to make the product. It

25:57

changes the thickness

25:59

of the coating by three times.

26:02

So all of your analytical methods

26:04

that you had, and this might

26:06

tie into Yeah. Lio as well.

26:09

All the analytical methods that are

26:11

validated. Okay. On

26:13

drug products today, throw 'em out

26:15

the window because they're based

26:17

on the tablet that exists today.

26:20

If you change an existing product to

26:22

now have three times as much coding, most

26:25

of your dissolution methods, most of

26:27

your analytical methods, your assays, everything

26:29

is gonna have to be redone revalidated.

26:32

So think of that implication. Mm-hmm. You're

26:34

gonna have all these manufacturing time,

26:37

uh, you know, costs and, and, uh,

26:39

implications that go in. Um,

26:41

and you're gonna have stability implications.

26:44

'cause many times if you do have a life sensitive,

26:47

uh, uh, a p i, you might

26:49

have to shorten the shelf life. Okay.

26:51

So all of those sort of negative

26:53

implications, you know, from

26:56

an operational standpoint with, with

26:58

material would come into play. At

27:01

the end of the day, you still have a product that is

27:03

not gonna be of the quality that

27:05

existed before, but you're gonna have put

27:07

an awful lot more cost into it, which

27:10

of course is going to have an impact on drug

27:12

pricing. Right. And, and you

27:14

know, obviously right now nobody wants to hear

27:16

about drug pricing going up. I

27:18

guarantee you that's what'll

27:20

happen if this span were to take place.

27:24

So that's one

27:25

impact on patients in the pharmaceutical,

27:27

in industry, um, you know, analytical

27:30

methods that are validated, getting thrown out the window,

27:32

prices going up. What other impacts would we

27:34

expect to see if this span were to take

27:36

place? Well, and, and, uh, you

27:38

know, uh, this is, this is,

27:40

uh, the scary part, okay?

27:43

Because the bottom line is just

27:46

in Europe alone, there are

27:48

91,000 drug

27:50

products on the market today that

27:53

contain titanium dioxide, 91,000.

27:57

Okay. Just think of that. Okay. Now,

28:00

if TIO O two were to be banned,

28:03

that means that 91,000

28:06

drug products have to be reformulated.

28:09

Okay? Now you think in the drug

28:11

world, what it takes to reformulate an

28:13

existing product, okay? Not

28:16

only redoing all the developmental

28:18

work, the stability work, the validation

28:20

work, all the analytical validation work,

28:23

then you've got the regulatory filings.

28:26

All of these changes would

28:28

be a qualitative and quantitative

28:31

change to the formulation, which

28:33

means in Europe, that

28:35

probably would be a type two variation.

28:38

Okay? Type two variations

28:41

are significant regulatory submissions,

28:43

post-approval, change submissions,

28:46

and even have a fee to do one,

28:48

it costs $103,000.

28:51

Just for a fee for getting e

28:53

m a to look at it. Now, that's just a filing

28:55

fee, not all the costs of doing all the

28:57

studies and the revalidation. Okay? So,

29:00

um, you know, 91,000

29:03

products would have to go through that.

29:06

Now the big question comes,

29:09

well, what would that really mean then in

29:11

terms of cost? Well, some analysis

29:13

has been done on that. The

29:16

expectation would be, it would cost between

29:18

one and one and a half million

29:21

euros for every

29:23

product that you would have to reformulate

29:25

if you can and remember some

29:28

of these products, you're not going to get, uh,

29:30

you're not gonna be able to reformulate and get

29:33

a same product, right? Uh, you

29:35

know, I've talked primarily about immediate release

29:37

applications. If you start thinking

29:39

about modified release applications,

29:42

most of them depend on the coding, or

29:44

at least a lot of 'em to release the

29:46

drug. So now, if you start putting more coding on.

29:49

You can't achieve the same release rate,

29:51

right? So there's technical implications,

29:53

but then you get into all of these

29:56

operational instability related things,

29:58

filing costs, et cetera, one

30:01

to one and a half million euros

30:03

per product. So if you were actually

30:05

going to try to reformulate all

30:07

91,000 drug products,

30:10

that even was possible, okay? You're

30:12

talking about, uh, approximately

30:14

$32 billion

30:17

that it would take to make this

30:19

change, okay? $32

30:22

billion. Now, I

30:24

guarantee you there are an awful lot of

30:26

medical issues we have out there

30:28

that could provide a lot more patient

30:31

safety benefits for $32

30:33

billion than spending

30:36

it on something where there's absolutely

30:38

no improvement in safety risk

30:40

to the patient, which

30:42

is what would happen here. Okay? Yeah. Uh,

30:44

so the reality, getting back to your question.

30:47

That, those are the facts. Okay?

30:50

That's what it would take if there were to

30:52

be a ban. The big question

30:54

comes, if you're a pharmaceutical company,

30:57

are you gonna reformulate? Okay?

31:00

And, um, you know, the

31:02

economics are gonna have to work. The economics

31:05

ultimately will dictate whether

31:07

somebody reformulates or

31:10

not, okay? And I guarantee

31:12

you many products, there will

31:14

be no economics to

31:16

drive such an expense, okay?

31:19

Especially if TIO

31:21

O two continues to be approved in other

31:23

parts of the world, okay? Where

31:25

the product you currently have is no problem,

31:27

right? So are you gonna really reformulate

31:29

and have a separate product for the European market

31:33

go through all this expense? No.

31:35

The answer is you are only

31:37

gonna reformulate products where it makes economic

31:40

sense. And what that means is

31:42

all of many of your older products,

31:45

Many of your low margin products, many

31:47

of your niche products, your orphan

31:49

drugs, drugs for pediatrics

31:52

and elderly, uh, that are small volume

31:54

products, there's gonna be no economic

31:57

justification. Those products will

31:59

simply be withdrawn. And I can tell you,

32:01

I've talked with many companies, 'cause I'm very much in

32:03

the middle of this whole thing, uh,

32:05

many companies are pretty certain they would

32:07

be withdrawing products if in fact

32:10

this happened. So what does that mean? We're

32:12

gonna start off with a situation where there's a perceived

32:15

safety risk, which is not true.

32:17

There is no safety risk and we're

32:19

gonna turn it into a real safety risk.

32:22

Where now we have patients that

32:24

can't get their medications in

32:27

Europe Okay. And

32:29

potentially elsewhere. Okay.

32:32

Because even if it continues

32:34

to be acceptable in other parts of

32:36

the world, if you're a major global

32:38

drug company and you have a. A

32:40

smaller volume product and

32:43

all of a sudden you take the European market

32:45

out of the equation and that amount

32:47

of sales, if you will, it may be

32:50

that it's no longer viable economically

32:52

for you to continue making that product, even

32:54

for the other markets where you don't have to

32:56

reformulate it because there's not

32:58

enough, you know, volume to

33:00

drive producing that product

33:02

and having a plant dedicated to it, et cetera.

33:05

So you could see people

33:07

around the world lose access

33:09

to products who, their government

33:12

doesn't have any problem with TIO O two, but

33:14

because of what Europe does, it could impact

33:16

a lot of people globally. So that,

33:19

that's really the key. When it comes to your question

33:21

about impact, there's lots of technical

33:23

implications, regulatory

33:25

filing implications, but the real

33:27

issue is patient access

33:29

to drugs is gonna be limited. And

33:32

then one last thing I'll mention, and then I'll shut

33:34

up for a minute, ask another question,

33:37

is the real question too is, Let's

33:39

just think about that number again. 91,000

33:42

drug products. Okay? How

33:45

many regulators is

33:47

E M A going to have to hire to

33:50

review 91,000 variation

33:53

submissions? Okay. There,

33:56

you know, there's been some estimates done

33:58

that even if they doubled their workforce,

34:01

it would probably take them 12 years

34:04

to go through that

34:06

many drug applications. Okay? So,

34:09

and, and of course that's meaning that like all

34:11

everybody's dedicated to doing these

34:13

change evaluations. What's gonna happen

34:15

to new drug development? You know, you

34:18

know, all, all the new drugs. Does that mean some of them

34:20

are now gonna get delayed? You could have people

34:22

losing their life because they don't have access to

34:24

new drugs, because instead

34:26

people are looking at these variations

34:29

and it's delaying the approval of the new drugs.

34:31

All of these things are potential to. Impacts

34:34

that this could have. So, you know, now

34:36

you kind of can understand my earlier comments.

34:38

This, this issue was huge

34:41

and you know, if there, if there was

34:43

an actual safety issue

34:45

with TIO two that was

34:48

credible, we all would be having

34:50

a different conversation. We would all be

34:52

saying, we gotta do whatever it takes. We gotta get

34:54

it out of there. But that's not

34:56

true when in fact there's

34:58

no good science that really justifies

35:00

this to even be having this discussion

35:03

is to some degree ludicrous. When

35:05

you think about the implications that we have

35:08

in the pharmaceutical arena, which is

35:10

obviously a lot more significant

35:12

than in the food arena where, you know, if

35:14

you lose a food product or you come up with a new

35:16

and improved, it's a different color, it's a different

35:18

product. I mean, that, that happens more routinely

35:21

in, in the food industry, doesn't

35:23

have the same implications of patients losing

35:25

their lifesaving drugs.

35:28

Absolutely. Yeah. Scary

35:30

to think of the impact there with very

35:32

little evidence behind it. Yep. Absolutely.

35:34

So, switching gears back to, you know,

35:36

the US and what's going

35:38

on here in, um, California, my former

35:41

home states, we hear about lawsuits and dolls

35:43

that have been pros requesting the

35:45

band of the same, um, titanium dioxide

35:48

in just California, which

35:50

honestly, California doesn't surprise me.

35:52

Yep. Well, exactly. And, and again,

35:54

this is, this is the effect of the media again.

35:56

And, and, uh, you know, um, let's

35:59

talk for a minute really about, uh, global,

36:02

you know, what do global regulators think about

36:04

this, right? We, we've talked about what's happened in Europe,

36:06

what's happening in Europe, or just

36:09

being discussed. Uh, a lot of

36:11

times I get asked, well, you know, how

36:13

does the f d a feel about that? How does, uh,

36:16

how, how does other regulators in other countries

36:18

feel about that? Well, the answer

36:20

to that is the F d A

36:23

has done their own thorough evaluation

36:25

of this. And they don't have

36:27

any safety concerns. And in fact,

36:29

they have, uh, you know, provided

36:32

public statements, uh,

36:35

showing that they actually think

36:37

that the whole approach that f c used

36:39

was incorrect. Okay.

36:41

Uh, so F D A in the US

36:44

has no concerns about TIO two in

36:46

terms of their evaluation. And

36:48

they did do a very recent valuation

36:51

of not only all the data that Efsa

36:53

looked at, but all the new data that's

36:55

been coming out as well. And they,

36:58

right off the bat, I mentioned earlier how

37:00

Efsa had looked at these nano grades

37:02

that don't really have anything to do with T O

37:04

two F D A. Looked at what

37:06

they did there and said, well, no, that's not relevant,

37:09

because that's not the material we're talking about.

37:12

You can't look at data gaps on a material

37:14

just because it's supposedly the same chemical,

37:17

but it's not the grades that have anything

37:19

to do with the material that

37:21

you're using here and apply that. 'cause it's,

37:23

they're not, it's apples and oranges. Right. So,

37:26

F D A made it clear that when

37:28

they looked at the studies on the pigment

37:30

grades of t TIO two, uh,

37:33

and taken everything into consideration, they

37:36

didn't have a concern. Uh,

37:38

same thing in health in, in

37:40

Canada. Okay. Uh, health

37:42

Canada actually went one step further. Not

37:44

only did they do a very thorough scientific

37:47

evaluation of this, they published

37:49

a large report, I forget how many

37:52

pages it is, 50 to a hundred pages. It's,

37:54

it's a big report. Um, uh,

37:56

basically on the safety of TIO two.

37:58

And after their assessment basically

38:01

came down as saying, We don't see

38:03

any concern with the safety of t

38:05

o two and, uh, you know, much

38:07

like F D A, uh, disagreed

38:09

that looking at these nano grades

38:11

should not be part of the consideration. And, you

38:13

know, from a toxicology standpoint, it's kind of irrelevant

38:16

ill information. Um,

38:18

and so Health Canada also said we

38:21

have no intent to take any action against TIO

38:23

two in a published report

38:25

that's out there on online, um,

38:28

Australia, New Zealand, their regulatory

38:30

agency called FSS a s uh, also

38:33

did their own evaluation here. Same

38:35

thing, published a report online. We've

38:38

looked at all the details. We don't see

38:40

any, uh, any issues. Um,

38:43

and interestingly enough, in the uk.

38:46

The Food Standards Authority, which

38:49

after Brexit, you know, the UK

38:51

is now on their own. Mm-hmm. Uh,

38:53

they don't necessarily have to just go along

38:55

with Europe all the time. Uh, they

38:57

do their own evaluations, uh,

38:59

and, uh, you know, the Food Standards

39:02

Authority, uh, did their own evaluation

39:04

after what FSA did. Uh,

39:07

and came to a different conclusion as well. And

39:09

they basically said, no, you know,

39:11

we don't see a safety problem with TIO two.

39:14

But they actually went one step further in the interim

39:16

report that they published, they're gonna have a final report

39:18

coming out next month, but they published

39:20

an interim report and they actually

39:23

were extremely critical of

39:25

the entire approach that FSSA took.

39:28

And basically said they felt

39:30

that what FSA has done is unnecessarily.

39:34

Concern the public over a situation

39:36

that should have never, you know, been

39:39

put out this way. It was rather

39:41

interesting to see how critical they were

39:43

in their report of ssa, which

39:45

they used to be part of. But

39:47

that kind of tells you, you know, nobody

39:50

else in the major countries

39:52

have a concern. And in Japan,

39:55

uh, there's a new study that just

39:57

came out recently. It's in the process of being

39:59

published where they actually looked

40:01

at even the nanoparticles that are smaller

40:03

than the ones that Efsa was worried about.

40:06

Uh, and, and that study was well

40:08

designed, came out totally clean. And

40:10

in Japan they also have said they don't have

40:12

any concern they're going to, they're gonna

40:14

go through a formal evaluation, but,

40:17

uh, based on what they know right now, they don't

40:19

see any concerns. So, major

40:22

countries, no problems.

40:25

There are a few countries that tend to be,

40:27

uh, Following, uh,

40:29

what Europe does, they don't really have

40:31

a, a large set of toxicology

40:33

experts on board, so they tend

40:35

to go along with Europe, uh, et

40:37

cetera. Uh, and so we've seen

40:39

some of the Middle Eastern countries also put

40:41

forward a ban. Um, basically

40:44

when you look at what they've said, they said, well, we're doing it

40:46

because Europe did it, right? Not because

40:49

they found more science. Okay. Um,

40:52

we've had some discussions through, uh,

40:54

the U S D A Foreign Agriculture

40:56

Service and the W T O with those

40:58

countries. And actually some

41:01

of those countries are now thinking of possibly

41:03

holding off and pausing the ban.

41:06

Okay. Uh, and, uh,

41:08

that said, excuse me, down in South

41:10

America and Visa,

41:13

shortly after, uh, FSSA

41:15

came out with their opinion, uh, and

41:17

Visa, um, sort

41:19

of had a knee jerk reaction saying, well, we,

41:21

maybe we should do it too, like Europe's doing it.

41:24

But we sent them a lot of information with some of these

41:26

facts. Uh, and the, and what

41:28

other regulators were saying, and they've now sort

41:30

of gone quiet, so nothing's happening

41:32

there yet. So the big thing is

41:35

the joint expert Committee on food

41:37

additives, which is the global

41:39

group that assesses the safety of food

41:41

additives. They're part of W H

41:43

O and F A O, they

41:45

have taken on to do a global safety

41:48

evaluation of all this data. They

41:50

are, they put out a call for data. Everybody

41:52

sent 'em all the information, including all this new

41:54

information. They are currently doing

41:57

that evaluation. They will have a meeting in September

42:00

or October, I forget this year, where

42:02

they're gonna be doing their own assessment, and

42:04

then they will publish a JVA opinion,

42:06

which will represent sort of the, the world

42:09

class toxicologists from all over the world.

42:12

So what we've tried to be telling a lot of these

42:14

other countries is don't go

42:16

and just ban it, because Europe did wait

42:18

and see what JVA has to

42:20

say. These are the world's best

42:22

toxicologists. And then based

42:24

on what they say, Make appropriate

42:27

decisions. So, you know, a lot of countries

42:29

seem to be in that mode now where they're gonna wait

42:31

to hear from Jfa, which is exactly what they

42:33

should do. That's why we have jva

42:35

to make these kinds of decisions. So, so

42:38

that's all in the process now. Now, getting

42:40

back to your initial question about California,

42:42

okay? Mm-hmm. That's another

42:45

interesting situations, to say the least. And, and

42:47

you said you lived in California before. Where, where

42:49

did you live in California? I grew up outside

42:52

la. Okay. Okay. Well,

42:54

and as you know, California always tends

42:56

to have, let's just say a little bit of a different

42:58

view on things. Um, prop

43:01

65, you, you name it. It's always

43:03

a Yes a little bit, you know, over the

43:05

top on some of these things, um,

43:07

uh, compared to some other states. Right? So

43:10

what's happened, two things started,

43:12

uh, there, there were, that got news

43:14

media attention. Okay? There was a couple

43:16

of lawsuits that came out last year.

43:19

Uh, one against Skittles.

43:22

Another on Tylenol that,

43:24

you know, basically what the, uh,

43:27

uh, the people filing a lawsuit said

43:29

was, well, you know, Europe has banned

43:31

this material and these companies

43:33

that make these products don't have a warning

43:35

label on their containers.

43:38

It contains, and they called it this toxic

43:40

material called titanium dioxide,

43:42

and nobody has called it toxic material.

43:44

And certainly even what SSA said,

43:47

never alluded to that, but

43:49

that's what these lawsuits said. And

43:51

basically, um, they, you

43:53

know, they were trying to sue these companies for, you

43:55

know, putting their, their consumers at risk

43:58

know they not having warning labels and stuff.

44:00

Well, long story short, the Skittles lawsuit

44:02

was thrown out pretty much the same thing

44:05

for Tylenol, but it got a lot of media

44:07

attention. Okay. Uh,

44:09

and of course if you talk to

44:12

the consumer on the street, you

44:14

know, you, a lot of people come up to

44:16

me, oh, they hear I'm involved in it. Oh, what about

44:18

these Skittles? Right? What about, and

44:21

it's like, I eat Skittles all the time.

44:23

I will continue. There is no issue with Skittles,

44:25

right? Uh, or any other of the food

44:27

products of many, which, which contain

44:29

TI two as well as the drugs. However,

44:32

what's now happened is the NGOs

44:35

who basically want to do

44:37

away with all food additives, pretty much they,

44:39

they don't like any of them. Um,

44:42

they hooked onto this issue. And,

44:45

uh, there's a particular assemblyman

44:47

in the assem, the, the, the state assembly

44:50

in California, uh,

44:52

who, uh, you know, it,

44:55

it was on a mission to get rid

44:57

of some of these additives. Titanium dioxide

44:59

is one of five additives that

45:02

he has a concern about. And

45:04

of course, when you dig into this bill,

45:06

that heap has proposed. You'll

45:08

find that there are several NGOs

45:12

that are the ones that are, uh,

45:14

uh, you know, doing, uh, uh, things

45:16

around the country on this now, uh,

45:19

who were trying to get rid of these additives,

45:21

right? For, you know, no good scientific

45:24

reason realistically, even though I think they think

45:26

there is. Um, and,

45:28

uh, unfortunately, this assemblyman in California

45:31

put forth a bill to ban

45:33

these five additives, of

45:35

which TIO two is one of foods.

45:38

Now, this is not a medicine thing, at least yet, um,

45:41

uh, in foods. And unfortunately,

45:44

he was very convincing. Uh,

45:46

and he got the house to approve

45:49

the bill, or not the house, the assembly.

45:51

Okay? Now that Bill has moved to

45:53

the Senate in California

45:56

where there's gonna be hearings that start,

45:58

I forget, it's either this week or next week. I. On

46:01

this bill, and of course, we're all trying to provide

46:03

them with a lot of the facts behind this

46:05

and some of the things I've talked about with you today,

46:08

um, uh, to hopefully convince

46:10

the Senate not to go forward

46:13

with this, okay? Uh, because,

46:15

uh, you know, if you, if you look at this,

46:17

this is a, this a whole different

46:19

issue. Now, if California

46:21

actually did ban this in

46:23

foods, you would've one state

46:27

in the country that doesn't allow

46:29

all the food products that all the other states allow.

46:32

Okay? How is that gonna

46:34

work from a trade perspective? You know?

46:37

Um, are companies really gonna

46:39

reformulate products just for California?

46:42

Okay. It's an important market, but, you

46:44

know, um, so,

46:47

so that's, uh, you know, sort of

46:49

a strange situation. And

46:51

if you really look at this, this

46:53

is a total affront

46:56

to f d a authority. On,

46:58

uh, protecting the public and,

47:00

and food safety regulation. Okay?

47:03

The F D A has the federal authority

47:06

to do these types of evaluations.

47:08

And the F D A has basically said, we

47:10

don't see a problem. Okay?

47:12

And we did evaluate recently

47:15

all the new data. The bill says

47:17

the F D A hasn't looked at this since the sixties.

47:20

Not true. They simply don't know

47:22

that the F D A has looked at this, right? Um,

47:25

but they passed it anyway in the assembly,

47:27

right? So, um, you

47:30

know, uh, you know, this,

47:32

if this gets approved, it will

47:34

be the first time that any state

47:37

has actually banned something that

47:40

F D A has said they don't have a problem

47:42

with. And you can start thinking about

47:45

the difficulties that, that may cause,

47:47

especially in today's world. If

47:49

certain states start

47:51

saying, well, we can do whatever we wanna do, regardless

47:54

of what the F D A says. And it,

47:56

and, and, and, and of course these

47:58

N G O groups that are behind this

48:01

have taken the same bill and

48:03

they started the similar bill. They found a

48:05

congressman in New York and

48:07

one in New Jersey to try

48:09

to have, uh, the same sort of bill. Now those

48:12

bills haven't really moved at

48:14

all yet, like the California one

48:16

is and hopefully won't 'cause they're not based

48:18

on any kind of good science. Um,

48:21

but you could start to see where you could have this

48:23

patchwork of regulation that would

48:25

be, from an industry perspective, impossible

48:29

to support. And like I

48:31

said, it's a direct challenge to f d

48:33

A authority, which could

48:36

start to affect, you know, drug

48:38

approvals and, uh, all kinds of other things.

48:40

If F D A is no longer the

48:42

authority that everybody goes to for

48:44

these kinds of decisions. So it's got

48:47

a lot of other hidden implications

48:49

that, um, uh, are not just

48:51

this one case.

48:53

Yeah. What can industry do

48:55

to fight these non-scientific

48:58

precautionary bans across states and

49:00

countries and try to continue the use

49:02

of titanium dioxide, which really seems

49:04

important to our drug and product, drug product

49:06

quality, and our food industry?

49:08

Yeah, no, I, I, i that it's

49:11

a difficult situation, I'll be honest with you. 'cause

49:13

when you get, when you get this

49:15

media, this negative media attention that

49:17

the, that, that the NGOs have

49:19

been able to stimulate here, even in the us

49:22

Uh, uh, and certainly it's what happened

49:24

in Europe before the science started to, you

49:26

know, kicked in, if you will. Um,

49:29

uh, you know, all

49:32

you can try to do is

49:34

educate, try to bring

49:36

the real science forward, run

49:38

additional studies that in fact may

49:40

answer any uncertainty questions that are out

49:42

there. But the difficulty we have is

49:45

that once it gets out into the

49:47

media and into some of this arena,

49:49

science no longer matters. Truth

49:52

and facts no longer matter as we've

49:54

seen with many things. Right? Um,

49:57

and that makes it very difficult to get

49:59

the messaging to the consumer

50:01

who ultimately is believing

50:04

what they're hearing sometimes. And so,

50:06

um, but that said, um,

50:08

you know, there are many efforts to

50:11

do exactly what I just talked about,

50:13

right? The industry, uh,

50:15

has put together a major

50:18

new science program, uh,

50:20

to, uh, run, you know, again,

50:22

millions of dollars of new studies.

50:25

Uh, To answer any possible

50:27

uncertainty that anybody still has

50:29

and all the things that have been brought up. Those

50:31

studies are underway. We've got

50:33

various industry groups, which I'm involved

50:35

with, almost all of them, uh, uh,

50:38

you know, that have formed different coalitions

50:40

and, uh, you know, joint, uh, association

50:43

groups, et cetera, where we're sharing

50:45

information and we're trying to utilize

50:47

this to make sure we're bringing all the facts

50:50

forward to the regulators around

50:52

the world who are making decisions on this,

50:55

and try to start figuring out

50:57

what kind of messaging can we put together

51:00

in a way that can get to consumers

51:02

as well. Uh, we've been having

51:04

conferences. I just coordinated a big conference

51:06

in Washington, DC last week where

51:09

world class toxicologists all came

51:11

in to talk about the real safety situation,

51:14

uh, and the impacts this would have if we went

51:16

to pharma. And we have a, we're putting

51:18

together a whole white paper coming out of that conference

51:21

to try to, again, bring these facts forward

51:23

to E M A. So they're aware

51:26

of the reality of

51:28

what a ban would mean so that they

51:31

think about that before they make a decision.

51:33

Uh, so there's many things in the

51:35

works, uh, you know, to try

51:37

to affect the outcome and

51:40

hopefully not see,

51:42

you know, this impact pharmaceuticals

51:44

anywhere, including Europe. Uh,

51:46

it may, it may be too late to

51:48

sort of save the food situation

51:50

in Europe, uh, because it's, uh,

51:53

politically be difficult for them to go back

51:55

on this at this point. But certainly

51:57

what we're trying to do is also influence

52:00

with facts and science regulators

52:02

in the rest of the world, not just to blindly

52:04

follow Europe, but to

52:06

in fact, see what Jfa says

52:09

based on good science and world-class

52:11

experts, and use that information

52:14

to base their decisions on.

52:18

As you're involved on the front lines on this issue,

52:21

do you have any final thoughts on the titanium

52:23

dioxide situation?

52:24

Yeah, uh uh. What I would say

52:27

to sort of finish off the discussion is here,

52:29

unfortunately, I wish it was

52:31

just a titanium dioxide situation, but

52:34

actually this is the tip

52:36

of the iceberg, okay? Because

52:39

what's happened now is many

52:42

materials that are common food additives

52:45

and pharmaceutical excipients contain

52:48

a certain portion of nano pardons. France,

52:52

as I mentioned earlier, is

52:54

worried, overly worried, in my opinion

52:57

about nanoparticles. Okay? They

53:00

have put together a list of 37.

53:03

Food additives, and many of them also are

53:05

form major pharmaceutical excipients, okay.

53:08

That are known to contain or thought

53:11

to contain nanoparticles

53:13

at some level. And they want

53:16

all of those materials to go through the

53:18

same evaluation by FSSA

53:20

in the same way that SSA did it,

53:22

using the same approach that they used.

53:26

Uh, looking at this nano, uh,

53:28

part, uh, you know, concern. Um,

53:30

and that, and that's, that's on

53:32

the horizon. So what happens

53:34

with titanium dioxide is going to set

53:37

a precedent that could

53:39

potentially impact many

53:41

of the most important excipients

53:44

that we have in the pharmaceutical industry

53:46

and also in the food industry, uh,

53:49

for similar reasons. Okay. Uh,

53:52

and just to give you an example of what

53:54

I'm talking about, I. Remember

53:56

those alternatives that I talked about that

53:58

people are looking at to try to use

54:01

and place a tio, O two, calcium carbonate,

54:03

iron oxides, try calcium

54:05

phosphate, iso malt. Guess

54:08

what? All of those are on the French

54:10

list of 37. Okay?

54:12

Oh, no. So all of those, in fact, iron

54:15

oxide is already under evaluation.

54:17

And I can tell you iron oxide does contain

54:20

nanoparticles. There

54:22

are no real, you know, safety issues that have

54:24

ever been documented with it. But there are,

54:27

you know, some of the, you know, when you start looking at

54:29

these nano things that, uh, people

54:32

worry about that, uh, go beyond science,

54:34

sometimes, uh, some of the same

54:36

concepts might come up in some people's minds.

54:39

And so, you know, these materials

54:41

are gonna get looked at by fsa

54:43

and if the same approach is used,

54:46

there's certainly the possibility that some

54:48

of those materials could through

54:50

the same kind of situation. Think

54:52

about the implications. If

54:54

the industry actually did

54:57

reformulate thousands

54:59

of products and millions or billions

55:01

of dollars and regulators, you

55:03

know, spend all this time to substitute

55:06

or try to utilize, uh, you know,

55:08

calcium carbonate alternative, even

55:10

though they're gonna have a, what I'll call a second class

55:12

product at the end. Okay. If they

55:14

do all of that, only to find

55:16

that two or three years later, calcium

55:19

carbonate or iron oxide, so I'm talking about, or

55:21

one of the alternatives that they've now used

55:25

is got the same problem. Now think

55:27

about what the implications that would have. Right? And,

55:29

uh, again, like I said earlier, if there

55:32

actually was a safety problem that's been

55:34

demonstrated, we'd all be having a different

55:36

discussion. That's simply not the case

55:38

here. Uh, much to

55:40

the NGO's chagrin, there's just no science

55:43

backing up their arguments on this. Um,

55:45

so, you know, I, I talk about

55:47

like these. Pigment type materials

55:50

that are used as alternatives to TIO two.

55:52

But let me just throw out a couple other excipients

55:55

that people who might be listening to this

55:57

might think, you know, somewhat

55:59

important to pharmaceuticals. Hmm.

56:02

Microcrystalline cellulose happens

56:04

to have nanoparticles and is on the French

56:07

list. Magnesium steroid.

56:09

Oh, on the French list. Mannitol

56:12

on the French list. I could

56:14

go on. Okay. Hmm. Microcrystalline,

56:16

cellulose and magnesium steroid. Probably

56:19

the most used fillers

56:22

and lubricants in the entire pharmaceutical

56:24

industry. Think of what would happen

56:26

if the same thing happened to them. Right.

56:29

So again, this, this is something where

56:31

we need to find a way. We need to pull out

56:33

the stops. Everybody in the industry

56:36

needs to get together, advocate,

56:39

do studies, do whatever we have to do, lobby,

56:42

et cetera, to make sure that

56:44

science somehow prevails. As

56:47

opposed to this, uh, overly

56:49

precautionary thinking that

56:52

is based on the precautionary principle,

56:54

which is commonly used in Europe,

56:56

especially in France. Um,

56:59

uh, uh, when we look at this,

57:01

otherwise, we're gonna have problems that go

57:03

way beyond what we're talking about today.

57:05

And this again, could be, like I said, the tip

57:07

of the iceberg. Um, and

57:09

so we've gotta, we've gotta find a way to nip this

57:12

in the butt and get science to win. Uh,

57:15

and not just media and politics

57:17

dictating where all this ends

57:19

up going. 'cause ultimately, at the end of the day,

57:21

this will be my last comment, patients

57:24

are at risk here. Patient safety

57:27

and availability of life-saving drugs

57:30

is, is the, is is what, uh,

57:32

you know, this is really all about. And

57:35

patients will suffer if there

57:37

were to be a ban. People

57:39

might think taking this nasty

57:41

stuff out of the drugs is

57:43

gonna somehow benefit them. There

57:46

will be no benefit even if you do reformulate

57:48

because there's no risk in the first place. Um,

57:52

however, there'd be a significant risk if you can't

57:54

get your drugs or

57:56

you can't afford them, or if you can't afford

57:58

them. And, you know, we talked about availability

58:00

here, but you're right, the cost issue.

58:02

Think of, uh, you know, if it does cost you

58:05

one to one and a half million dollars to reformulate,

58:08

who do you think is gonna pay for that? Do

58:10

you think that SS are just gonna absorb

58:12

all that? No, you know, drug,

58:14

drug prices will go up and,

58:17

and that is, that, that's anti what

58:19

everybody wants, including the government. Right.

58:22

Um, that needs to be thought

58:24

about, you know? Yeah. We hear, we see all the pressure

58:26

here in the US as well about lowering

58:29

drug costs. You know,

58:31

what would happen? This is counter to that. Yeah, exactly.

58:33

And, and if you think about even the, the politicians

58:36

who sort of drove some of this in Europe

58:39

in terms of the ban, okay. They

58:41

probably thought this is what would

58:43

get them. Votes with the voters

58:45

because, oh, we're keeping this nasty stuff

58:48

out of your food products. Okay.

58:50

Um, that's a kind

58:52

of short-term thinking, I think, because

58:55

if, if you're that politician and

58:57

all of a sudden it comes out in the media

59:00

that your decision on this is

59:02

now the reason that all of your,

59:04

your voters can no longer get their drugs,

59:07

I have a feeling that what

59:10

they thought was a good idea is not gonna get

59:12

them elected in the long term. You

59:15

know, because, you know, not having access

59:17

to these drugs, which will happen, by

59:19

the way. Okay. I mean, the one thing I can say

59:22

that I can absolutely say I'm certain

59:24

of is 91,000

59:26

drug products will not be

59:28

all reformulated. That is simply

59:31

not going to happen. It's not even possible

59:33

for that to happen. So

59:35

if that's true, what does that mean? There

59:37

will be drug shortages.

59:40

Probably on many drugs more than

59:42

there are today. And that's one of the biggest problems

59:44

you hear about these days. Talk to a doctor,

59:47

you know, and, and I, and I plan to talk

59:49

to doctors and nurses and others about this.

59:52

What do you think about this? You know, how

59:54

would you like this to have this effect? We

59:56

need to get them on board and, and we plan to.

1:00:00

That's great. And so normally

1:00:03

we wrap this podcast with a question about where

1:00:05

we would find you in a bookstore, but as we're both

1:00:07

skiers, I thought I would ask, what

1:00:09

slopes would I be most likely to find you on this

1:00:11

next ski season? Hmm.

1:00:13

Good question. Good question. Well, I'm

1:00:15

actually running a big trip for

1:00:18

the Eastern Pennsylvania Ski Council to

1:00:20

Val Gardena, Italy in the Dolomites,

1:00:23

um, in, uh, in the beginning

1:00:25

of March, this coming sea season. So

1:00:28

I'd love to see, uh, in the Dolomites, that's,

1:00:30

uh, certainly one place I'll be. And

1:00:32

then the other, uh, big trip I have, uh,

1:00:34

uh, that I'm, uh, assistant trip

1:00:37

leader on is a big trip, uh, for

1:00:39

our council to go to, uh, uh,

1:00:41

heavenly out in Lake Tahoe. So I'll

1:00:43

be going out to California as well. Uh,

1:00:45

and, and hopefully I'll be able to have, you

1:00:47

know, my, uh, my food with Tia

1:00:50

two in it when I get there. Uh, but,

1:00:53

uh, so you know, I'll be, uh, skiing

1:00:55

in beautiful Lake Tahoe as well. How about yourself?

1:00:57

Do you have something planned? I

1:00:59

ski here

1:00:59

locally in Colorado. Oh, I heard, I forgot.

1:01:02

I've not done Steamboat Springs. That's, uh, on

1:01:04

my list here to one of my last ones I

1:01:06

haven't done here in Colorado. Oh, you haven't

1:01:07

done Steamboat yet? I haven't done Steamboat yet.

1:01:09

You, you, you've gotta do that actually in

1:01:11

2025 we'll be running a trip to

1:01:13

Steamboat, so, um, maybe

1:01:15

run tea out there then. Yeah.

1:01:17

And we can catch up on, on the latest on

1:01:19

titanium dioxide

1:01:20

then. Absolutely. And, and hopefully we'll

1:01:22

have more positive news to talk about at that point.

1:01:25

Yes. Well, it's been enlightening

1:01:27

conversation today, Dave. I really appreciate

1:01:29

you joining us today on the podcast. Um,

1:01:33

well, thanks a lot for the opportunity to, to talk

1:01:35

to you about this topic. As you can tell, I'm,

1:01:37

uh, I'm a little bit passionate about it because

1:01:39

I've, uh, I've seen what the, the downside

1:01:42

of this could be and, uh, um,

1:01:44

it's a serious issue that unfortunately not

1:01:46

everybody in the pharmaceutical industry really

1:01:49

understands what's going on yet

1:01:51

and, and the implications it could have. So

1:01:53

we we're trying to get everybody.

1:01:56

Fired up on this issue to understand the

1:01:58

facts and, and everybody get together

1:02:00

and get aligned on how we can, uh, make

1:02:03

sure this goes down the right pathway. Great.

1:02:06

If our

1:02:06

listeners want to learn more or get involved,

1:02:08

where can they go to learn more about you and

1:02:10

Black Diamond Consulting and how

1:02:12

to get involved in titanium dioxide?

1:02:14

Well, the easiest thing to do would be to go to my

1:02:16

website, which is, uh, uh,

1:02:19

uh, htpp s

1:02:21

slash like normal, and then just black diamond

1:02:23

regulatory.com. Great.

1:02:26

We'll post

1:02:27

that

1:02:27

in the show notes. Thanks so much for joining us today,

1:02:29

Dave. Great.

1:02:30

Well, thank you very much for the opportunity, and again,

1:02:32

uh, for those of you who were listening to this,

1:02:34

uh, hopefully this was, uh, educational to you

1:02:36

and brought some, uh, things to light that

1:02:38

maybe you didn't fully understand. And

1:02:40

if you do, um, want more information,

1:02:43

please let me know. I'd be glad to, to help you

1:02:45

with that.