Regulatory Open Forum

This message was posted by a user wishing to remain anonymous

Hello Everyone!

I'm trying to find some opinions/answers around this topic. I can't find anything on the FDA website or currently discussed in any of these or other forums about how a product would be handled if you are using an OTC monographed ingredient, but not making any of the drug claims available for that ingredient.

There are some that on the surface seem pretty obvious as being an adulterated drugs such as using sal acid at 2% in a cleanser but avoiding any acne verbiage. But, there is nothing concrete (at least that I've found) that says this would in fact be violating the CFR if at a minimum the intended use for acne can't be proven. 

The real area though that seems significantly grey is using ingredients such as dimethicone, colloidal oatmeal, allantoin, glycerin, menthol, UV filters and a myriad of others. All of these ingredients are readily used in cosmetics, and at what point does it start to transition from a simple a cosmetic to more of a drug? In several cases I've seen identical use levels of an ingredient where one product is a drug and the other product is a cosmetic, and with the regulatory differences between the two the costs savings for doing one over the other can be substantial.

With all that said, in your opinion or experience, only referencing monographed ingredients, and only looking at the US market, at what point is the cosmetic to drug threshold crossed? Is it just marketing? Is it ingredient use level? Is it ingredient dependent?

Hi Anon.

The answer to this in my opinion is relatively simple overall - the difference is the claims made.  As you noted, several different ingredients are routinely used in the production of cosmetics that also could be considered API items for OTC products.  In this case, per numerous presentations from FDA the real tell is the label and labeling of the product.  If the product were to make only cosmetics claims then the product would be treated like a cosmetic for regulatory purposes.  However, you must be extremely careful with the wording of the claims.  I can't tell you over the past 25 years how many times I have seen companies get into regulatory issues because of careless wording of claims that change what could easily be considered a cosmetic claim into a drug claim with the addition or deletion of a single word or phrase on the claim.  That said, using things like tadalafil in a cosmetic would pretty easily be seen as potentially adulterating the cosmetic because it is an FDA approved Rx (A)NDA active ingredient that likely would have no reasonable basis as a cosmetic ingredient.  However, even in your 2% salicylic acid example above, you could theoretically argue that the ingredient is providing preservative benefit to the formulation and provided you didn't make any claim on the ingredient activity under anti-acne or anti-dandruff monographs you could be OK.  Remember the only thing that could potentially cause a review by FDA would be the fact that this ingredient might end up so high on the ingredient list of cosmetics that it flags and triggers a question.  FDA does not at this time require that percentages of anything be reported to FDA for cosmetics (actually the cosmetics reporting program itself is voluntary) so it cannot require that level of detail be provided anywhere else.  The only rule on this is that all ingredients in the formula at 1% or greater must be listed in descending order of predominance.  After that, technically it can become a "free for all" how you list your ingredients that are not at or above 1%.  

Remember - the driver of the differences is the claims.  If you want to speak to acne issues then you are a drug, must have the required level of the active ingredient(s) (or be within the range allowed) or have a previously approved (A)NDA for OTC use, label with the drug facts box required language, have all the GMP programs in place and audited and be auditable, register and list the products with FDA, etc.  If you just want to speak to an exfoliating claim (completely cosmetic so long as the product does not get into claims with acne or dandruff or psoriasis, etc.) then you simply list your product ingredients according to the rules.  It really isn't that confusing in concept how this would work.  But as with seemingly everything else in regulatory affairs, the devils are in the details.  So if your company is trying to figure out how to do a product with OTC active ingredients in the formula without going the OTC route, you really need to be extremely careful of the wording of the labeling.  For this reason you also need to be certain you have a good understanding of the types of claims that the FDA is allowing on the OTC products that might use the active ingredient(s) you are planning to use so that you can avoid the problem.

Just as an example of this I will take you dimethicone active ingredient above.  For cosmetic purposes (remember cosmetics can only be applied externally to the body so I will only concentrate the example on external/topical application items here) that ingredient can be used as a humectant or a film forming material that would aid in providing moisturization to the skin.  Moisturization as such is a cosmetic claim.  However, you need to be careful of what I call "claim expansion" or "claim extension" in this case because dimethicone is also an approved API in the skin protectant monograph.  Because of this, if you were to say something like "moisturizes and soothes chapped skin due to wind or cold" you would, in my opinion, pretty quickly slip from being a cosmetic (moisturizer) to an OTC (skin protectant) because you are now speaking to conditions that start to link your product to the monograph language.  This might be arguable.  But if you said "heals your skin" (e.g. "heal your chapped skin") you pretty much have crossed the line.

Please feel free to email me with any specific issues.  I realize that this is a bit verbose of an answer for what I said was pretty simple conceptually but just trying to provide some specific examples to explain the overarching concept.

------------------------------
Victor Mencarelli
Director Regulatory Affairs
United States
------------------------------

Original Message:
Sent: 21-Jun-2019 13:38
From: Anonymous Member
Subject: Using API without Drug Claims for Cosmetics

This message was posted by a user wishing to remain anonymous

Hello Everyone!

I'm trying to find some opinions/answers around this topic. I can't find anything on the FDA website or currently discussed in any of these or other forums about how a product would be handled if you are using an OTC monographed ingredient, but not making any of the drug claims available for that ingredient.

There are some that on the surface seem pretty obvious as being an adulterated drugs such as using sal acid at 2% in a cleanser but avoiding any acne verbiage. But, there is nothing concrete (at least that I've found) that says this would in fact be violating the CFR if at a minimum the intended use for acne can't be proven.

The real area though that seems significantly grey is using ingredients such as dimethicone, colloidal oatmeal, allantoin, glycerin, menthol, UV filters and a myriad of others. All of these ingredients are readily used in cosmetics, and at what point does it start to transition from a simple a cosmetic to more of a drug? In several cases I've seen identical use levels of an ingredient where one product is a drug and the other product is a cosmetic, and with the regulatory differences between the two the costs savings for doing one over the other can be substantial.

With all that said, in your opinion or experience, only referencing monographed ingredients, and only looking at the US market, at what point is the cosmetic to drug threshold crossed? Is it just marketing? Is it ingredient use level? Is it ingredient dependent?

Agree with Victor. The distinction is based upon the narrative used. This is why I always feel that Regulatory should be involved at the inception phase of product development to assist/mentor marketing on the desired claims for use in all labeling formats. And, also be aware that FTC gets involved in OTC advertising. One suggestion, leverage the FTC guidances of Truth in Advertising and FPLA when constructing labels and advertising.

------------------------------
[Robert] [Falcone]
[Integris3Biosolutions]
[Bedminster] [NJ]
[US]
------------------------------

Original Message:
Sent: 21-Jun-2019 13:38
From: Anonymous Member
Subject: Using API without Drug Claims for Cosmetics

This message was posted by a user wishing to remain anonymous

Hello Everyone!

I'm trying to find some opinions/answers around this topic. I can't find anything on the FDA website or currently discussed in any of these or other forums about how a product would be handled if you are using an OTC monographed ingredient, but not making any of the drug claims available for that ingredient.

There are some that on the surface seem pretty obvious as being an adulterated drugs such as using sal acid at 2% in a cleanser but avoiding any acne verbiage. But, there is nothing concrete (at least that I've found) that says this would in fact be violating the CFR if at a minimum the intended use for acne can't be proven.

The real area though that seems significantly grey is using ingredients such as dimethicone, colloidal oatmeal, allantoin, glycerin, menthol, UV filters and a myriad of others. All of these ingredients are readily used in cosmetics, and at what point does it start to transition from a simple a cosmetic to more of a drug? In several cases I've seen identical use levels of an ingredient where one product is a drug and the other product is a cosmetic, and with the regulatory differences between the two the costs savings for doing one over the other can be substantial.

With all that said, in your opinion or experience, only referencing monographed ingredients, and only looking at the US market, at what point is the cosmetic to drug threshold crossed? Is it just marketing? Is it ingredient use level? Is it ingredient dependent?

But does it quack like a duck?

This comes up time and again.  It's very true and I agree with other posters here that the claims are central to the product positioning.  But if you have a product with an active ingredient which is likely to have a significant medicinal effect, or for example a device which provides a diagnostic measurement, then the regulator will treat it accordingly, and no amount of silence on actives present, or disclaimers of "not for diagnostic use"will change that.

If it quacks like a duck, don't claim it's a turkey.

Arthur

------------------------------
Arthur Brandwood PhD FRAPS
Founder and Principal Consultant
Brandwood Biomedical
Sydney, Australia
Arthur@brandwoodbiomedical.com
------------------------------

Original Message:
Sent: 22-Jun-2019 15:03
From: Robert Falcone
Subject: Using API without Drug Claims for Cosmetics

Agree with Victor. The distinction is based upon the narrative used. This is why I always feel that Regulatory should be involved at the inception phase of product development to assist/mentor marketing on the desired claims for use in all labeling formats. And, also be aware that FTC gets involved in OTC advertising. One suggestion, leverage the FTC guidances of Truth in Advertising and FPLA when constructing labels and advertising.

------------------------------
[Robert] [Falcone]
[Integris3Biosolutions]
[Bedminster] [NJ]
[US]

Original Message:
Sent: 21-Jun-2019 13:38
From: Anonymous Member
Subject: Using API without Drug Claims for Cosmetics

This message was posted by a user wishing to remain anonymous

Hello Everyone!

I'm trying to find some opinions/answers around this topic. I can't find anything on the FDA website or currently discussed in any of these or other forums about how a product would be handled if you are using an OTC monographed ingredient, but not making any of the drug claims available for that ingredient.

There are some that on the surface seem pretty obvious as being an adulterated drugs such as using sal acid at 2% in a cleanser but avoiding any acne verbiage. But, there is nothing concrete (at least that I've found) that says this would in fact be violating the CFR if at a minimum the intended use for acne can't be proven.

The real area though that seems significantly grey is using ingredients such as dimethicone, colloidal oatmeal, allantoin, glycerin, menthol, UV filters and a myriad of others. All of these ingredients are readily used in cosmetics, and at what point does it start to transition from a simple a cosmetic to more of a drug? In several cases I've seen identical use levels of an ingredient where one product is a drug and the other product is a cosmetic, and with the regulatory differences between the two the costs savings for doing one over the other can be substantial.

With all that said, in your opinion or experience, only referencing monographed ingredients, and only looking at the US market, at what point is the cosmetic to drug threshold crossed? Is it just marketing? Is it ingredient use level? Is it ingredient dependent?

Original Message------

But does it quack like a duck?

This comes up time and again.  It's very true and I agree with other posters here that the claims are central to the product positioning.  But if you have a product with an active ingredient which is likely to have a significant medicinal effect, or for example a device which provides a diagnostic measurement, then the regulator will treat it accordingly, and no amount of silence on actives present, or disclaimers of "not for diagnostic use"will change that.

If it quacks like a duck, don't claim it's a turkey.

Arthur

------------------------------
Arthur Brandwood PhD FRAPS
Founder and Principal Consultant
Brandwood Biomedical
Sydney, Australia
Arthur@brandwoodbiomedical.com
------------------------------

Original Message------

But does it quack like a duck?

This comes up time and again.  It's very true and I agree with other posters here that the claims are central to the product positioning.  But if you have a product with an active ingredient which is likely to have a significant medicinal effect, or for example a device which provides a diagnostic measurement, then the regulator will treat it accordingly, and no amount of silence on actives present, or disclaimers of "not for diagnostic use"will change that.

If it quacks like a duck, don't claim it's a turkey.

Arthur

------------------------------
Arthur Brandwood PhD FRAPS
Founder and Principal Consultant
Brandwood Biomedical
Sydney, Australia
Arthur@brandwoodbiomedical.com
------------------------------

Thank you Arthur for that. 

Yes, I am just waiting for more cosmetics with hormones,  (testosterone or estrogen) or other known medicinal compounds with active effect to be out there, unregulated.  That is only the natural progression of things, just the path supplement and homeopathics have taken. 

There are just not enough enforcement resources to catch all these companies who say "oops, our bad, but we didn't make any claims, wink, wink".

This is of course, also rampant in medical devices, especially in digital health now.



------------------------------
Ginger Cantor, MBA, RAC
Founder/Principal Consultant
Centaur Consulting LLC
River Falls, Wisconsin 54022 USA
715-307-1850
centaurconsultingllc@gmail.com
------------------------------

Original Message:
Sent: 24-Jun-2019 21:22
From: Arthur Brandwood
Subject: Using API without Drug Claims for Cosmetics

But does it quack like a duck?

This comes up time and again.  It's very true and I agree with other posters here that the claims are central to the product positioning.  But if you have a product with an active ingredient which is likely to have a significant medicinal effect, or for example a device which provides a diagnostic measurement, then the regulator will treat it accordingly, and no amount of silence on actives present, or disclaimers of "not for diagnostic use"will change that.

If it quacks like a duck, don't claim it's a turkey.

Arthur

------------------------------
Arthur Brandwood PhD FRAPS
Founder and Principal Consultant
Brandwood Biomedical
Sydney, Australia
Arthur@brandwoodbiomedical.com

Original Message:
Sent: 22-Jun-2019 15:03
From: Robert Falcone
Subject: Using API without Drug Claims for Cosmetics

Agree with Victor. The distinction is based upon the narrative used. This is why I always feel that Regulatory should be involved at the inception phase of product development to assist/mentor marketing on the desired claims for use in all labeling formats. And, also be aware that FTC gets involved in OTC advertising. One suggestion, leverage the FTC guidances of Truth in Advertising and FPLA when constructing labels and advertising.

------------------------------
[Robert] [Falcone]
[Integris3Biosolutions]
[Bedminster] [NJ]
[US]

Original Message:
Sent: 21-Jun-2019 13:38
From: Anonymous Member
Subject: Using API without Drug Claims for Cosmetics

This message was posted by a user wishing to remain anonymous

Hello Everyone!

I'm trying to find some opinions/answers around this topic. I can't find anything on the FDA website or currently discussed in any of these or other forums about how a product would be handled if you are using an OTC monographed ingredient, but not making any of the drug claims available for that ingredient.

There are some that on the surface seem pretty obvious as being an adulterated drugs such as using sal acid at 2% in a cleanser but avoiding any acne verbiage. But, there is nothing concrete (at least that I've found) that says this would in fact be violating the CFR if at a minimum the intended use for acne can't be proven.

The real area though that seems significantly grey is using ingredients such as dimethicone, colloidal oatmeal, allantoin, glycerin, menthol, UV filters and a myriad of others. All of these ingredients are readily used in cosmetics, and at what point does it start to transition from a simple a cosmetic to more of a drug? In several cases I've seen identical use levels of an ingredient where one product is a drug and the other product is a cosmetic, and with the regulatory differences between the two the costs savings for doing one over the other can be substantial.

With all that said, in your opinion or experience, only referencing monographed ingredients, and only looking at the US market, at what point is the cosmetic to drug threshold crossed? Is it just marketing? Is it ingredient use level? Is it ingredient dependent?

I am in total agreement,  An API or drug placed in a cosmetic should be declared as such.  There are exceptions but these are few and far between.

------------------------------
Robert Schiff PhD, RAC, CQA, FRAPS
CEO
Schiff & Company, Inc.
1120 Bloomfield Ave., Suite 103
West Caldwell, NJ 07006
rschiff13@aol.com
973-568-3361
------------------------------

Original Message:
Sent: 25-Jun-2019 07:59
From: Ginger Cantor
Subject: Using API without Drug Claims for Cosmetics

Thank you Arthur for that.

Yes, I am just waiting for more cosmetics with hormones,  (testosterone or estrogen) or other known medicinal compounds with active effect to be out there, unregulated.  That is only the natural progression of things, just the path supplement and homeopathics have taken.

There are just not enough enforcement resources to catch all these companies who say "oops, our bad, but we didn't make any claims, wink, wink".

This is of course, also rampant in medical devices, especially in digital health now.



------------------------------
Ginger Cantor, MBA, RAC
Founder/Principal Consultant
Centaur Consulting LLC
River Falls, Wisconsin 54022 USA
715-307-1850
centaurconsultingllc@gmail.com

Original Message:
Sent: 24-Jun-2019 21:22
From: Arthur Brandwood
Subject: Using API without Drug Claims for Cosmetics

But does it quack like a duck?

This comes up time and again.  It's very true and I agree with other posters here that the claims are central to the product positioning.  But if you have a product with an active ingredient which is likely to have a significant medicinal effect, or for example a device which provides a diagnostic measurement, then the regulator will treat it accordingly, and no amount of silence on actives present, or disclaimers of "not for diagnostic use"will change that.

If it quacks like a duck, don't claim it's a turkey.

Arthur

------------------------------
Arthur Brandwood PhD FRAPS
Founder and Principal Consultant
Brandwood Biomedical
Sydney, Australia
Arthur@brandwoodbiomedical.com

Original Message:
Sent: 22-Jun-2019 15:03
From: Robert Falcone
Subject: Using API without Drug Claims for Cosmetics

Agree with Victor. The distinction is based upon the narrative used. This is why I always feel that Regulatory should be involved at the inception phase of product development to assist/mentor marketing on the desired claims for use in all labeling formats. And, also be aware that FTC gets involved in OTC advertising. One suggestion, leverage the FTC guidances of Truth in Advertising and FPLA when constructing labels and advertising.

------------------------------
[Robert] [Falcone]
[Integris3Biosolutions]
[Bedminster] [NJ]
[US]

Original Message:
Sent: 21-Jun-2019 13:38
From: Anonymous Member
Subject: Using API without Drug Claims for Cosmetics

This message was posted by a user wishing to remain anonymous

Hello Everyone!

I'm trying to find some opinions/answers around this topic. I can't find anything on the FDA website or currently discussed in any of these or other forums about how a product would be handled if you are using an OTC monographed ingredient, but not making any of the drug claims available for that ingredient.

There are some that on the surface seem pretty obvious as being an adulterated drugs such as using sal acid at 2% in a cleanser but avoiding any acne verbiage. But, there is nothing concrete (at least that I've found) that says this would in fact be violating the CFR if at a minimum the intended use for acne can't be proven.

The real area though that seems significantly grey is using ingredients such as dimethicone, colloidal oatmeal, allantoin, glycerin, menthol, UV filters and a myriad of others. All of these ingredients are readily used in cosmetics, and at what point does it start to transition from a simple a cosmetic to more of a drug? In several cases I've seen identical use levels of an ingredient where one product is a drug and the other product is a cosmetic, and with the regulatory differences between the two the costs savings for doing one over the other can be substantial.

With all that said, in your opinion or experience, only referencing monographed ingredients, and only looking at the US market, at what point is the cosmetic to drug threshold crossed? Is it just marketing? Is it ingredient use level? Is it ingredient dependent?

There are two issues.  The first are the claims which have been well discussed.  The second is if there is a drug API in the cosmetic formulation and no drug claim is made then how does the manufacturer account for the purpose of the API if asked?  This is as very sticky situation.  As Rob and I recently participated in a public forum where it was discussed, there are diverse opinions.

------------------------------
Robert Schiff PhD, RAC, CQA, FRAPS
CEO
Schiff & Company, Inc.
1120 Bloomfield Ave., Suite 103
West Caldwell, NJ 07006
rschiff13@aol.com
973-568-3361
------------------------------

Original Message:
Sent: 21-Jun-2019 13:38
From: Anonymous Member
Subject: Using API without Drug Claims for Cosmetics

This message was posted by a user wishing to remain anonymous

Hello Everyone!

I'm trying to find some opinions/answers around this topic. I can't find anything on the FDA website or currently discussed in any of these or other forums about how a product would be handled if you are using an OTC monographed ingredient, but not making any of the drug claims available for that ingredient.

There are some that on the surface seem pretty obvious as being an adulterated drugs such as using sal acid at 2% in a cleanser but avoiding any acne verbiage. But, there is nothing concrete (at least that I've found) that says this would in fact be violating the CFR if at a minimum the intended use for acne can't be proven.

The real area though that seems significantly grey is using ingredients such as dimethicone, colloidal oatmeal, allantoin, glycerin, menthol, UV filters and a myriad of others. All of these ingredients are readily used in cosmetics, and at what point does it start to transition from a simple a cosmetic to more of a drug? In several cases I've seen identical use levels of an ingredient where one product is a drug and the other product is a cosmetic, and with the regulatory differences between the two the costs savings for doing one over the other can be substantial.

With all that said, in your opinion or experience, only referencing monographed ingredients, and only looking at the US market, at what point is the cosmetic to drug threshold crossed? Is it just marketing? Is it ingredient use level? Is it ingredient dependent?

Original Message------

There are two issues.  The first are the claims which have been well discussed.  The second is if there is a drug API in the cosmetic formulation and no drug claim is made then how does the manufacturer account for the purpose of the API if asked?  This is as very sticky situation.  As Rob and I recently participated in a public forum where it was discussed, there are diverse opinions.

------------------------------
Robert Schiff PhD, RAC, CQA, FRAPS
CEO
Schiff & Company, Inc.
1120 Bloomfield Ave., Suite 103
West Caldwell, NJ 07006
rschiff13@aol.com
973-568-3361
------------------------------

Hi All,

A discussion is useful when we are supported by facts.  I appreciate Rob Falcone's suggestion.  I would recommend before a discussion or as part of one, a list of regulatory and/or legal documents that discuss placement of APIs and/or drugs in cosmetics without claims.  For example if no claims are the drugs listed first on the panels or buried in the cosmetic ingredient list.  Then how does one support the presence of the API or drug without a claim.  Note that the API or drug in the cosmetic is at the level approved for use in the quantity as a drug.   In our practice we are asked this question quite frequently.  We are also very familiar with Warning Letters concerning this situation.

We would appreciate any list of documents or citations in the USC , CFR, guidances, etc. which discuss this situation; especially where possible AEs and warnings are involved.  Information outside the US will be very helpful.

------------------------------
Robert Schiff PhD, RAC, CQA, FRAPS
CEO
Schiff & Company, Inc.
1120 Bloomfield Ave., Suite 103
West Caldwell, NJ 07006
rschiff13@aol.com
973-568-3361
------------------------------

Original Message:
Sent: 23-Jun-2019 16:45
From: Robert Falcone
Subject: Using API without Drug Claims for Cosmetics

Will everyone be interested in participating in a meeting discussing all aspects of OTC products

Sent from my iPhone

Original Message------

There are two issues.  The first are the claims which have been well discussed.  The second is if there is a drug API in the cosmetic formulation and no drug claim is made then how does the manufacturer account for the purpose of the API if asked?  This is as very sticky situation.  As Rob and I recently participated in a public forum where it was discussed, there are diverse opinions.

------------------------------
Robert Schiff PhD, RAC, CQA, FRAPS
CEO
Schiff & Company, Inc.
1120 Bloomfield Ave., Suite 103
West Caldwell, NJ 07006
rschiff13@aol.com
973-568-3361
------------------------------

Hi Robert.

My position on this is simple.  The facts are that cosmetics can use any ingredient provided there is a reason for the ingredient (other than the API use) and the ingredient and formulation are considered to be safe for that intended use, at the intended levels in the product, and for the product category itself.

While I fully agree that there have been several instances in the past that have landed companies in some hot water with FDA, the fact is that many of the allowed active ingredients listed in OTC monographs have also been used in cosmetic products for decades for other purposes.  Let's take a few examples below that I can speak to directly (just so that we aren't speaking in over-generalized terms and I apologize if any of this sounds like it is too elementary - just trying to level set here):

1. Glycerin.  This is an ingredient that has been used in cosmetic products at levels over 50% for decades.  The purpose of the ingredient generally in cosmetics is as a humectant and a moisturizer.  FDA has never, to my knowledge, considered the inclusion of glycerin in a cosmetic product as indicative of the product's true purpose being that of a drug absent other indications of that purpose (claims made on the product leaching into the OTC world, etc.).  That said, glycerin is an allowed OTC API in several different OTC monographs including oral demulcents and even skin protectants.  I think this is a strong case that just including an ingredient that is allowed as an OTC API doesn't necessarily mean that the FDA will have issues.

2. Salicylic Acid.  This is an ingredient again that has been used in cosmetics for a long time.  The ingredient can be used for adjusting pH or even as an effective exfoliating ingredient.  It is also allowed in the OTC world as an anti-acne, anti-dandruff, anti-psoriasis API at levels as low as 0.5%.  Again, absent other indications that the ingredient is ​intended to produce or elicit a drug effect on the body, I am not aware of FDA having taken any action on this ingredient ever.

3. Titanium Dioxide.  This has been used in cosmetics products since the origination of color cosmetics from what I can tell.  The purpose of this in a cosmetic is to allow the color pallet to be "dialed" to provide different shades of the same "base color" across different specific formulations.  It can also be used as a bulking agent to allow for more consistent production of pressed powders.  In addition to this Titanium Dioxide is used as an API in the sunscreen monograph "up to 25%" which implies that any level up to and including 25% could be considered a drug API.  However, once again, I am not aware of FDA challenging products with titanium dioxide as unapproved (or even unlisted) drug products absent some other indication in the labeling that the product is intended as a drug.

4. Dimethicone.  The ingredient is often used in cosmetics as a slip modifier, a hair or skin conditioning agent or a film forming agent with the purpose of ensuring that the product helps prevent moisture loss from the skin.  Again, this is also a skin protectant API but absent some other indication of drug purpose, the simple inclusion of this ingredient in the formulation ingredient list has never, to my knowledge, caused FDA to challenge a product as a drug.

These are just 4 specific examples I can think of off the top of my head that would substantiate that just because something is listed in the OTC API listings it doesn't necessarily mean that the resulting product is a "drug" in the definitions in both 21 USC and 21 CFR.  This said, as I noted earlier on in the discussion, the use of an API that is a prescription API would likely cause a significant discussion between the company and the FDA.  So addition of something like tadalifil in a cosmetic is going to get FDA's attention pretty quickly.  But the cases of that in my opinion are extremely rare and few and far between.  Most of the other issues I suspect you have seen specifically include issues around the use of the API from a monograph and then someone trying to get a little too cute for FDA's liking in the way they market the product.  This invariably seems to cause FDA to see the product as being a drug product which ultimately is found to be mislabeled because it is missing the drug facts labeling that is required for OTC monograph items and even might be outside the scope of the monograph (either the API level could be too high or even too low to make the claims).

Also, keep in mind that 21 CFR 701 et seq does contain a specific listing of ingredients that cannot form part of a cosmetic product ever.  You will notice if you look at this listing that I believe it only contains something like a dozen or so items and none of them are actually APIs nor is there a specific mention of APIs in this listing at this point.  While FDA could always find with sufficient evidence that the product is an unapproved new drug for any of the GMP reasons they still need to show that somehow there is a connection between the product and some representation in the labeling that the product is meant to be a drug.  Otherwise, I would guess 99% of all cosmetic products on the market today would require drug facts labeling because almost every product I have ever been involved in working on in the past 25+ years in the cosmetics area has had at least 1 OTC API in the ingredient listing and most every one has had the OTC API at the levels allowed under the monograph rules to act as a drug.  The reason that they haven't been called out as drugs was the fact that the claims made on labeling did not rise to the level of drug claims.

Sorry for the seeming dissertation on this one.  I did not intend for this to get nearly this long.  But I thought it would be somewhat helpful.  I apologize if I have mistakenly categorized this as helpful....

------------------------------
Victor Mencarelli
Director Regulatory Affairs
United States
------------------------------

Original Message:
Sent: 24-Jun-2019 07:17
From: Robert Schiff
Subject: Using API without Drug Claims for Cosmetics

Hi All,

A discussion is useful when we are supported by facts.  I appreciate Rob Falcone's suggestion.  I would recommend before a discussion or as part of one, a list of regulatory and/or legal documents that discuss placement of APIs and/or drugs in cosmetics without claims.  For example if no claims are the drugs listed first on the panels or buried in the cosmetic ingredient list.  Then how does one support the presence of the API or drug without a claim.  Note that the API or drug in the cosmetic is at the level approved for use in the quantity as a drug.   In our practice we are asked this question quite frequently.  We are also very familiar with Warning Letters concerning this situation.

We would appreciate any list of documents or citations in the USC , CFR, guidances, etc. which discuss this situation; especially where possible AEs and warnings are involved.  Information outside the US will be very helpful.

------------------------------
Robert Schiff PhD, RAC, CQA, FRAPS
CEO
Schiff & Company, Inc.
1120 Bloomfield Ave., Suite 103
West Caldwell, NJ 07006
rschiff13@aol.com
973-568-3361

Original Message:
Sent: 23-Jun-2019 16:45
From: Robert Falcone
Subject: Using API without Drug Claims for Cosmetics

Will everyone be interested in participating in a meeting discussing all aspects of OTC products

Sent from my iPhone

Original Message------

There are two issues.  The first are the claims which have been well discussed.  The second is if there is a drug API in the cosmetic formulation and no drug claim is made then how does the manufacturer account for the purpose of the API if asked?  This is as very sticky situation.  As Rob and I recently participated in a public forum where it was discussed, there are diverse opinions.

------------------------------
Robert Schiff PhD, RAC, CQA, FRAPS
CEO
Schiff & Company, Inc.
1120 Bloomfield Ave., Suite 103
West Caldwell, NJ 07006
rschiff13@aol.com
973-568-3361
------------------------------

Original Message------

Hi Robert.

My position on this is simple.  The facts are that cosmetics can use any ingredient provided there is a reason for the ingredient (other than the API use) and the ingredient and formulation are considered to be safe for that intended use, at the intended levels in the product, and for the product category itself.

While I fully agree that there have been several instances in the past that have landed companies in some hot water with FDA, the fact is that many of the allowed active ingredients listed in OTC monographs have also been used in cosmetic products for decades for other purposes.  Let's take a few examples below that I can speak to directly (just so that we aren't speaking in over-generalized terms and I apologize if any of this sounds like it is too elementary - just trying to level set here):

1. Glycerin.  This is an ingredient that has been used in cosmetic products at levels over 50% for decades.  The purpose of the ingredient generally in cosmetics is as a humectant and a moisturizer.  FDA has never, to my knowledge, considered the inclusion of glycerin in a cosmetic product as indicative of the product's true purpose being that of a drug absent other indications of that purpose (claims made on the product leaching into the OTC world, etc.).  That said, glycerin is an allowed OTC API in several different OTC monographs including oral demulcents and even skin protectants.  I think this is a strong case that just including an ingredient that is allowed as an OTC API doesn't necessarily mean that the FDA will have issues.

2. Salicylic Acid.  This is an ingredient again that has been used in cosmetics for a long time.  The ingredient can be used for adjusting pH or even as an effective exfoliating ingredient.  It is also allowed in the OTC world as an anti-acne, anti-dandruff, anti-psoriasis API at levels as low as 0.5%.  Again, absent other indications that the ingredient is ​intended to produce or elicit a drug effect on the body, I am not aware of FDA having taken any action on this ingredient ever.

3. Titanium Dioxide.  This has been used in cosmetics products since the origination of color cosmetics from what I can tell.  The purpose of this in a cosmetic is to allow the color pallet to be "dialed" to provide different shades of the same "base color" across different specific formulations.  It can also be used as a bulking agent to allow for more consistent production of pressed powders.  In addition to this Titanium Dioxide is used as an API in the sunscreen monograph "up to 25%" which implies that any level up to and including 25% could be considered a drug API.  However, once again, I am not aware of FDA challenging products with titanium dioxide as unapproved (or even unlisted) drug products absent some other indication in the labeling that the product is intended as a drug.

4. Dimethicone.  The ingredient is often used in cosmetics as a slip modifier, a hair or skin conditioning agent or a film forming agent with the purpose of ensuring that the product helps prevent moisture loss from the skin.  Again, this is also a skin protectant API but absent some other indication of drug purpose, the simple inclusion of this ingredient in the formulation ingredient list has never, to my knowledge, caused FDA to challenge a product as a drug.

These are just 4 specific examples I can think of off the top of my head that would substantiate that just because something is listed in the OTC API listings it doesn't necessarily mean that the resulting product is a "drug" in the definitions in both 21 USC and 21 CFR.  This said, as I noted earlier on in the discussion, the use of an API that is a prescription API would likely cause a significant discussion between the company and the FDA.  So addition of something like tadalifil in a cosmetic is going to get FDA's attention pretty quickly.  But the cases of that in my opinion are extremely rare and few and far between.  Most of the other issues I suspect you have seen specifically include issues around the use of the API from a monograph and then someone trying to get a little too cute for FDA's liking in the way they market the product.  This invariably seems to cause FDA to see the product as being a drug product which ultimately is found to be mislabeled because it is missing the drug facts labeling that is required for OTC monograph items and even might be outside the scope of the monograph (either the API level could be too high or even too low to make the claims).

Also, keep in mind that 21 CFR 701 et seq does contain a specific listing of ingredients that cannot form part of a cosmetic product ever.  You will notice if you look at this listing that I believe it only contains something like a dozen or so items and none of them are actually APIs nor is there a specific mention of APIs in this listing at this point.  While FDA could always find with sufficient evidence that the product is an unapproved new drug for any of the GMP reasons they still need to show that somehow there is a connection between the product and some representation in the labeling that the product is meant to be a drug.  Otherwise, I would guess 99% of all cosmetic products on the market today would require drug facts labeling because almost every product I have ever been involved in working on in the past 25+ years in the cosmetics area has had at least 1 OTC API in the ingredient listing and most every one has had the OTC API at the levels allowed under the monograph rules to act as a drug.  The reason that they haven't been called out as drugs was the fact that the claims made on labeling did not rise to the level of drug claims.

Sorry for the seeming dissertation on this one.  I did not intend for this to get nearly this long.  But I thought it would be somewhat helpful.  I apologize if I have mistakenly categorized this as helpful....

------------------------------
Victor Mencarelli
Director Regulatory Affairs
United States
------------------------------

Original Message------

Hi Robert.

My position on this is simple.  The facts are that cosmetics can use any ingredient provided there is a reason for the ingredient (other than the API use) and the ingredient and formulation are considered to be safe for that intended use, at the intended levels in the product, and for the product category itself.

While I fully agree that there have been several instances in the past that have landed companies in some hot water with FDA, the fact is that many of the allowed active ingredients listed in OTC monographs have also been used in cosmetic products for decades for other purposes.  Let's take a few examples below that I can speak to directly (just so that we aren't speaking in over-generalized terms and I apologize if any of this sounds like it is too elementary - just trying to level set here):

1. Glycerin.  This is an ingredient that has been used in cosmetic products at levels over 50% for decades.  The purpose of the ingredient generally in cosmetics is as a humectant and a moisturizer.  FDA has never, to my knowledge, considered the inclusion of glycerin in a cosmetic product as indicative of the product's true purpose being that of a drug absent other indications of that purpose (claims made on the product leaching into the OTC world, etc.).  That said, glycerin is an allowed OTC API in several different OTC monographs including oral demulcents and even skin protectants.  I think this is a strong case that just including an ingredient that is allowed as an OTC API doesn't necessarily mean that the FDA will have issues.

2. Salicylic Acid.  This is an ingredient again that has been used in cosmetics for a long time.  The ingredient can be used for adjusting pH or even as an effective exfoliating ingredient.  It is also allowed in the OTC world as an anti-acne, anti-dandruff, anti-psoriasis API at levels as low as 0.5%.  Again, absent other indications that the ingredient is ​intended to produce or elicit a drug effect on the body, I am not aware of FDA having taken any action on this ingredient ever.

3. Titanium Dioxide.  This has been used in cosmetics products since the origination of color cosmetics from what I can tell.  The purpose of this in a cosmetic is to allow the color pallet to be "dialed" to provide different shades of the same "base color" across different specific formulations.  It can also be used as a bulking agent to allow for more consistent production of pressed powders.  In addition to this Titanium Dioxide is used as an API in the sunscreen monograph "up to 25%" which implies that any level up to and including 25% could be considered a drug API.  However, once again, I am not aware of FDA challenging products with titanium dioxide as unapproved (or even unlisted) drug products absent some other indication in the labeling that the product is intended as a drug.

4. Dimethicone.  The ingredient is often used in cosmetics as a slip modifier, a hair or skin conditioning agent or a film forming agent with the purpose of ensuring that the product helps prevent moisture loss from the skin.  Again, this is also a skin protectant API but absent some other indication of drug purpose, the simple inclusion of this ingredient in the formulation ingredient list has never, to my knowledge, caused FDA to challenge a product as a drug.

These are just 4 specific examples I can think of off the top of my head that would substantiate that just because something is listed in the OTC API listings it doesn't necessarily mean that the resulting product is a "drug" in the definitions in both 21 USC and 21 CFR.  This said, as I noted earlier on in the discussion, the use of an API that is a prescription API would likely cause a significant discussion between the company and the FDA.  So addition of something like tadalifil in a cosmetic is going to get FDA's attention pretty quickly.  But the cases of that in my opinion are extremely rare and few and far between.  Most of the other issues I suspect you have seen specifically include issues around the use of the API from a monograph and then someone trying to get a little too cute for FDA's liking in the way they market the product.  This invariably seems to cause FDA to see the product as being a drug product which ultimately is found to be mislabeled because it is missing the drug facts labeling that is required for OTC monograph items and even might be outside the scope of the monograph (either the API level could be too high or even too low to make the claims).

Also, keep in mind that 21 CFR 701 et seq does contain a specific listing of ingredients that cannot form part of a cosmetic product ever.  You will notice if you look at this listing that I believe it only contains something like a dozen or so items and none of them are actually APIs nor is there a specific mention of APIs in this listing at this point.  While FDA could always find with sufficient evidence that the product is an unapproved new drug for any of the GMP reasons they still need to show that somehow there is a connection between the product and some representation in the labeling that the product is meant to be a drug.  Otherwise, I would guess 99% of all cosmetic products on the market today would require drug facts labeling because almost every product I have ever been involved in working on in the past 25+ years in the cosmetics area has had at least 1 OTC API in the ingredient listing and most every one has had the OTC API at the levels allowed under the monograph rules to act as a drug.  The reason that they haven't been called out as drugs was the fact that the claims made on labeling did not rise to the level of drug claims.

Sorry for the seeming dissertation on this one.  I did not intend for this to get nearly this long.  But I thought it would be somewhat helpful.  I apologize if I have mistakenly categorized this as helpful....

------------------------------
Victor Mencarelli
Director Regulatory Affairs
United States
------------------------------

Agreed Robert!

------------------------------
Ginger Cantor, MBA, RAC
Founder/Principal Consultant
Centaur Consulting LLC
River Falls, Wisconsin 54022 USA
715-307-1850
centaurconsultingllc@gmail.com
------------------------------

Original Message:
Sent: 26-Jun-2019 17:24
From: Robert Falcone
Subject: Using API without Drug Claims for Cosmetics

As stated in a previous email, all the emails clearly show the need to consider starting a topical group to share and discuss this particular area. There is the misguided belief in the cosmetic and personal care industries (excluding OTCs) that they are not "regulated" and just today, the FDA published a very extensive list of warning letters issued in the last 3 years to Cosmetic companies for blurring the difference between drugs and cosmetic claims. And it is also a bit of a failure for RAPS not to educate the cosmetic regulatory folks. This is why it is becoming quite pressing for us as regulatory affairs professionals to help our brethren in the cosmetic field to be better informed.

Original Message------

Hi Robert.

My position on this is simple.  The facts are that cosmetics can use any ingredient provided there is a reason for the ingredient (other than the API use) and the ingredient and formulation are considered to be safe for that intended use, at the intended levels in the product, and for the product category itself.

While I fully agree that there have been several instances in the past that have landed companies in some hot water with FDA, the fact is that many of the allowed active ingredients listed in OTC monographs have also been used in cosmetic products for decades for other purposes.  Let's take a few examples below that I can speak to directly (just so that we aren't speaking in over-generalized terms and I apologize if any of this sounds like it is too elementary - just trying to level set here):

1. Glycerin.  This is an ingredient that has been used in cosmetic products at levels over 50% for decades.  The purpose of the ingredient generally in cosmetics is as a humectant and a moisturizer.  FDA has never, to my knowledge, considered the inclusion of glycerin in a cosmetic product as indicative of the product's true purpose being that of a drug absent other indications of that purpose (claims made on the product leaching into the OTC world, etc.).  That said, glycerin is an allowed OTC API in several different OTC monographs including oral demulcents and even skin protectants.  I think this is a strong case that just including an ingredient that is allowed as an OTC API doesn't necessarily mean that the FDA will have issues.

2. Salicylic Acid.  This is an ingredient again that has been used in cosmetics for a long time.  The ingredient can be used for adjusting pH or even as an effective exfoliating ingredient.  It is also allowed in the OTC world as an anti-acne, anti-dandruff, anti-psoriasis API at levels as low as 0.5%.  Again, absent other indications that the ingredient is ​intended to produce or elicit a drug effect on the body, I am not aware of FDA having taken any action on this ingredient ever.

3. Titanium Dioxide.  This has been used in cosmetics products since the origination of color cosmetics from what I can tell.  The purpose of this in a cosmetic is to allow the color pallet to be "dialed" to provide different shades of the same "base color" across different specific formulations.  It can also be used as a bulking agent to allow for more consistent production of pressed powders.  In addition to this Titanium Dioxide is used as an API in the sunscreen monograph "up to 25%" which implies that any level up to and including 25% could be considered a drug API.  However, once again, I am not aware of FDA challenging products with titanium dioxide as unapproved (or even unlisted) drug products absent some other indication in the labeling that the product is intended as a drug.

4. Dimethicone.  The ingredient is often used in cosmetics as a slip modifier, a hair or skin conditioning agent or a film forming agent with the purpose of ensuring that the product helps prevent moisture loss from the skin.  Again, this is also a skin protectant API but absent some other indication of drug purpose, the simple inclusion of this ingredient in the formulation ingredient list has never, to my knowledge, caused FDA to challenge a product as a drug.

These are just 4 specific examples I can think of off the top of my head that would substantiate that just because something is listed in the OTC API listings it doesn't necessarily mean that the resulting product is a "drug" in the definitions in both 21 USC and 21 CFR.  This said, as I noted earlier on in the discussion, the use of an API that is a prescription API would likely cause a significant discussion between the company and the FDA.  So addition of something like tadalifil in a cosmetic is going to get FDA's attention pretty quickly.  But the cases of that in my opinion are extremely rare and few and far between.  Most of the other issues I suspect you have seen specifically include issues around the use of the API from a monograph and then someone trying to get a little too cute for FDA's liking in the way they market the product.  This invariably seems to cause FDA to see the product as being a drug product which ultimately is found to be mislabeled because it is missing the drug facts labeling that is required for OTC monograph items and even might be outside the scope of the monograph (either the API level could be too high or even too low to make the claims).

Also, keep in mind that 21 CFR 701 et seq does contain a specific listing of ingredients that cannot form part of a cosmetic product ever.  You will notice if you look at this listing that I believe it only contains something like a dozen or so items and none of them are actually APIs nor is there a specific mention of APIs in this listing at this point.  While FDA could always find with sufficient evidence that the product is an unapproved new drug for any of the GMP reasons they still need to show that somehow there is a connection between the product and some representation in the labeling that the product is meant to be a drug.  Otherwise, I would guess 99% of all cosmetic products on the market today would require drug facts labeling because almost every product I have ever been involved in working on in the past 25+ years in the cosmetics area has had at least 1 OTC API in the ingredient listing and most every one has had the OTC API at the levels allowed under the monograph rules to act as a drug.  The reason that they haven't been called out as drugs was the fact that the claims made on labeling did not rise to the level of drug claims.

Sorry for the seeming dissertation on this one.  I did not intend for this to get nearly this long.  But I thought it would be somewhat helpful.  I apologize if I have mistakenly categorized this as helpful....

------------------------------
Victor Mencarelli
Director Regulatory Affairs
United States
------------------------------

Original Message------

As stated in a previous email, all the emails clearly show the need to consider starting a topical group to share and discuss this particular area. There is the misguided belief in the cosmetic and personal care industries (excluding OTCs) that they are not "regulated" and just today, the FDA published a very extensive list of warning letters issued in the last 3 years to Cosmetic companies for blurring the difference between drugs and cosmetic claims. And it is also a bit of a failure for RAPS not to educate the cosmetic regulatory folks. This is why it is becoming quite pressing for us as regulatory affairs professionals to help our brethren in the cosmetic field to be better informed.

Hi Robert.

I am happy to discuss this issue further.  In fact, this is an area that seems to get very little attention from RAPS in general because the issues around submissions and more "formal Regulatory" areas (NDA, ANDA, Devices, etc.) seem to take more of a limelight level.  Might be from the interests or the experiences of the group in terms of who is posting here, but I have long said that the society is of value to the world precisely because of the diversity of the products that we all theoretically could work on within the FDA umbrella.

Maybe a set of topics for Convergence?​

------------------------------
Victor Mencarelli
Director Regulatory Affairs
United States
------------------------------

Original Message:
Sent: 23-Jun-2019 16:45
From: Robert Falcone
Subject: Using API without Drug Claims for Cosmetics

Will everyone be interested in participating in a meeting discussing all aspects of OTC products

Sent from my iPhone

Original Message------

There are two issues.  The first are the claims which have been well discussed.  The second is if there is a drug API in the cosmetic formulation and no drug claim is made then how does the manufacturer account for the purpose of the API if asked?  This is as very sticky situation.  As Rob and I recently participated in a public forum where it was discussed, there are diverse opinions.

------------------------------
Robert Schiff PhD, RAC, CQA, FRAPS
CEO
Schiff & Company, Inc.
1120 Bloomfield Ave., Suite 103
West Caldwell, NJ 07006
rschiff13@aol.com
973-568-3361
------------------------------

Original Message------

Hi Robert.

I am happy to discuss this issue further.  In fact, this is an area that seems to get very little attention from RAPS in general because the issues around submissions and more "formal Regulatory" areas (NDA, ANDA, Devices, etc.) seem to take more of a limelight level.  Might be from the interests or the experiences of the group in terms of who is posting here, but I have long said that the society is of value to the world precisely because of the diversity of the products that we all theoretically could work on within the FDA umbrella.

Maybe a set of topics for Convergence?​

------------------------------
Victor Mencarelli
Director Regulatory Affairs
United States
------------------------------

Original Message------

Hi Victor,

I wil not be at the RAPS meeting and have also issued another response which you may find helpful about documentation.

All the best,

Bob

Robert Schiff, PhD, RAC, CQA, FRAPS
President and CEO
Schiff & Company, Inc.
1120 Bloomfield Avenue, Suite 103
West Caldwell, NJ 07006

Tel 973-227-1830
Fax  & Conference Line 973-227-5330
Cell 973-568-3361
www.SchiffandCompany.com

Celebrating 37 Years (1982-2019) of service in Compliance, Regulatory Affairs and Clinical Research

I completely agree with Arthur and Ginger. "If it looks like a duck, and acts like a duck, then it is a duck."

FDA's web page says, "Intended use may be established in a number of ways.... 
Also, it would be difficult to justify the use of an API at therapeutic levels in a cosmetic product. A common example is Salicylic Acid at 2% in a skin cleanser that is not labeled as an antibacterial drug. Or to use a known sunscreen API in an "anti-aging" skin cream at levels higher than those needed to protect the product from light. While FDA would not know the concentration unless they checked the batch card, when they inspect or when they review a cosmetic ingredient statement submitted to the Voluntary Cosmetic Reporting Program, they will ask the question: what is the cosmetic purpose of this ingredient? There should be a known and credible cosmetic function. 

Therefore, my regulatory opinion is that the classification is driven by the intended use, ... and the inclusion of a known drug ingredient. The recognition of the ingredient as a drug may be an implied claim, for example using a known antimicrobial drug active in a hand soap labeled as a cosmetic. Certain ingredients -- such as Ginger's example of hormones -- would attract attention.

------------------------------
Jennifer R. Martin
Director - Regulatory Affairs
United States
------------------------------

Original Message:
Sent: 21-Jun-2019 13:38
From: Anonymous Member
Subject: Using API without Drug Claims for Cosmetics

This message was posted by a user wishing to remain anonymous

Hello Everyone!

I'm trying to find some opinions/answers around this topic. I can't find anything on the FDA website or currently discussed in any of these or other forums about how a product would be handled if you are using an OTC monographed ingredient, but not making any of the drug claims available for that ingredient.

There are some that on the surface seem pretty obvious as being an adulterated drugs such as using sal acid at 2% in a cleanser but avoiding any acne verbiage. But, there is nothing concrete (at least that I've found) that says this would in fact be violating the CFR if at a minimum the intended use for acne can't be proven.

The real area though that seems significantly grey is using ingredients such as dimethicone, colloidal oatmeal, allantoin, glycerin, menthol, UV filters and a myriad of others. All of these ingredients are readily used in cosmetics, and at what point does it start to transition from a simple a cosmetic to more of a drug? In several cases I've seen identical use levels of an ingredient where one product is a drug and the other product is a cosmetic, and with the regulatory differences between the two the costs savings for doing one over the other can be substantial.

With all that said, in your opinion or experience, only referencing monographed ingredients, and only looking at the US market, at what point is the cosmetic to drug threshold crossed? Is it just marketing? Is it ingredient use level? Is it ingredient dependent?