Regulatory Open Forum

Hello  ,

I need guidance for OTC drug product ,having already available OTC monograph.

What are manufacturing criteria and documents we need to prepare for inspection ?

How we design specification if we consider oral tablet dosage form?

Is there any specific guidance for stability study for OTC monograph product?

Regards,

Sapna

Hi Sapna.

First rule - OTC are drugs just like any other prescription product.  Therefore, all of the general requirements for drug products attach to OTC products as well.  So you would handle this in exactly the same manner as you would handle production of any other oral tablet dosage form that would require a healthcare provider's prior approval/prescription to obtain.  Also, regarding FDA, they have the same requirements for documentation and stability as the agency would expect for any other type of drug product.  It is a misunderstanding (potentially significant from a regulatory perspective) to believe that the FDA will allow OTC products to avoid things that other manufacturers of drug products must comply with.  The only difference between OTC monograph drugs and any other drug product on the market is the elimination of the pre-approval of the FDA to market these drugs.

More importantly, this allowance only applies to products compliant to the monograph in formula (active ingredient, levels and allowable combinations), dosage form (if FDA specifies that the allowed dosage forms are liquids and tablets but you decide to create a powder the FDA could consider your product a "new drug" if you don't go through the full FDA pre-approval process!) and labeling (if you change the labeling of any required statement noted within quotation marks on the monograph you are asking to have an issues with the FDA.  While truthful and non-misleading statements are allowed (it states this in just about every monograph I have ever read!) it is also still a little risky to include any statements in the label that do not come from the monograph because whether a statement is "truthful and not misleading" can be debated depending on the presentation and exact language of the statement.

For specifications I would start with the applicable chapter in the USP for tablet dosage forms.  This is a simple way to ensure that you are doing at least enough testing to provide FDA with an understanding that you take your product and your responsibility as a manufacturer seriously.  Generally I would look to things like dissolution time, homogeneity of the powder and the tablets themselves, hardness, if time release then checking the consistency of the release across time, etc.  This is in addition to the fairly standard "color, appearance, scoring, marking" requirements that would be significant.

Hope some of this helps!

Hello  ,

I need guidance for OTC drug product ,having already available OTC monograph.

What are manufacturing criteria and documents we need to prepare for inspection ?

How we design specification if we consider oral tablet dosage form?

Is there any specific guidance for stability study for OTC monograph product?

Regards,

Sapna

Is it require accelerated and long term data of 6 months minimum on three batches to establish shelf life for OTC monograph products? 

Do it require to generate on R&D batches or commercial batches?

Also do we need to complete process validation studies before we put product in market?

Hi Sapna.

First rule - OTC are drugs just like any other prescription product.  Therefore, all of the general requirements for drug products attach to OTC products as well.  So you would handle this in exactly the same manner as you would handle production of any other oral tablet dosage form that would require a healthcare provider's prior approval/prescription to obtain.  Also, regarding FDA, they have the same requirements for documentation and stability as the agency would expect for any other type of drug product.  It is a misunderstanding (potentially significant from a regulatory perspective) to believe that the FDA will allow OTC products to avoid things that other manufacturers of drug products must comply with.  The only difference between OTC monograph drugs and any other drug product on the market is the elimination of the pre-approval of the FDA to market these drugs.

More importantly, this allowance only applies to products compliant to the monograph in formula (active ingredient, levels and allowable combinations), dosage form (if FDA specifies that the allowed dosage forms are liquids and tablets but you decide to create a powder the FDA could consider your product a "new drug" if you don't go through the full FDA pre-approval process!) and labeling (if you change the labeling of any required statement noted within quotation marks on the monograph you are asking to have an issues with the FDA.  While truthful and non-misleading statements are allowed (it states this in just about every monograph I have ever read!) it is also still a little risky to include any statements in the label that do not come from the monograph because whether a statement is "truthful and not misleading" can be debated depending on the presentation and exact language of the statement.

For specifications I would start with the applicable chapter in the USP for tablet dosage forms.  This is a simple way to ensure that you are doing at least enough testing to provide FDA with an understanding that you take your product and your responsibility as a manufacturer seriously.  Generally I would look to things like dissolution time, homogeneity of the powder and the tablets themselves, hardness, if time release then checking the consistency of the release across time, etc.  This is in addition to the fairly standard "color, appearance, scoring, marking" requirements that would be significant.

Hope some of this helps!

Hello  ,

I need guidance for OTC drug product ,having already available OTC monograph.

What are manufacturing criteria and documents we need to prepare for inspection ?

How we design specification if we consider oral tablet dosage form?

Is there any specific guidance for stability study for OTC monograph product?

Regards,

Sapna

Hi Sapna.

First rule - OTC are drugs just like any other prescription product.  Therefore, all of the general requirements for drug products attach to OTC products as well.  So you would handle this in exactly the same manner as you would handle production of any other oral tablet dosage form that would require a healthcare provider's prior approval/prescription to obtain.  Also, regarding FDA, they have the same requirements for documentation and stability as the agency would expect for any other type of drug product.  It is a misunderstanding (potentially significant from a regulatory perspective) to believe that the FDA will allow OTC products to avoid things that other manufacturers of drug products must comply with.  The only difference between OTC monograph drugs and any other drug product on the market is the elimination of the pre-approval of the FDA to market these drugs.

More importantly, this allowance only applies to products compliant to the monograph in formula (active ingredient, levels and allowable combinations), dosage form (if FDA specifies that the allowed dosage forms are liquids and tablets but you decide to create a powder the FDA could consider your product a "new drug" if you don't go through the full FDA pre-approval process!) and labeling (if you change the labeling of any required statement noted within quotation marks on the monograph you are asking to have an issues with the FDA.  While truthful and non-misleading statements are allowed (it states this in just about every monograph I have ever read!) it is also still a little risky to include any statements in the label that do not come from the monograph because whether a statement is "truthful and not misleading" can be debated depending on the presentation and exact language of the statement.

For specifications I would start with the applicable chapter in the USP for tablet dosage forms.  This is a simple way to ensure that you are doing at least enough testing to provide FDA with an understanding that you take your product and your responsibility as a manufacturer seriously.  Generally I would look to things like dissolution time, homogeneity of the powder and the tablets themselves, hardness, if time release then checking the consistency of the release across time, etc.  This is in addition to the fairly standard "color, appearance, scoring, marking" requirements that would be significant.

Hope some of this helps!

Hello  ,

I need guidance for OTC drug product ,having already available OTC monograph.

What are manufacturing criteria and documents we need to prepare for inspection ?

How we design specification if we consider oral tablet dosage form?

Is there any specific guidance for stability study for OTC monograph product?

Regards,

Sapna

Dear Experts,

Thank you for your valuable input on the topics.

Would you please clarify below points (when product is available in final OTC monograph),

• Does it required to prepare a eCTD for OTC? what are the modules applicable/ not applicable for OTC?
• What will be the submission gateway?
• Does it required to take any number like NDA/ANDA?
• Is the there any fees involvement with OTC submission?
• When we can start marketing? immediately after submission and Drug listing or we have to wait for certain period?
• Does a GDUFA listed facility have to pay any additional fees?

I am looking for a complete guidance for OTC submission to USFDA.

Hi Sapna.

First rule - OTC are drugs just like any other prescription product.  Therefore, all of the general requirements for drug products attach to OTC products as well.  So you would handle this in exactly the same manner as you would handle production of any other oral tablet dosage form that would require a healthcare provider's prior approval/prescription to obtain.  Also, regarding FDA, they have the same requirements for documentation and stability as the agency would expect for any other type of drug product.  It is a misunderstanding (potentially significant from a regulatory perspective) to believe that the FDA will allow OTC products to avoid things that other manufacturers of drug products must comply with.  The only difference between OTC monograph drugs and any other drug product on the market is the elimination of the pre-approval of the FDA to market these drugs.

More importantly, this allowance only applies to products compliant to the monograph in formula (active ingredient, levels and allowable combinations), dosage form (if FDA specifies that the allowed dosage forms are liquids and tablets but you decide to create a powder the FDA could consider your product a "new drug" if you don't go through the full FDA pre-approval process!) and labeling (if you change the labeling of any required statement noted within quotation marks on the monograph you are asking to have an issues with the FDA.  While truthful and non-misleading statements are allowed (it states this in just about every monograph I have ever read!) it is also still a little risky to include any statements in the label that do not come from the monograph because whether a statement is "truthful and not misleading" can be debated depending on the presentation and exact language of the statement.

For specifications I would start with the applicable chapter in the USP for tablet dosage forms.  This is a simple way to ensure that you are doing at least enough testing to provide FDA with an understanding that you take your product and your responsibility as a manufacturer seriously.  Generally I would look to things like dissolution time, homogeneity of the powder and the tablets themselves, hardness, if time release then checking the consistency of the release across time, etc.  This is in addition to the fairly standard "color, appearance, scoring, marking" requirements that would be significant.

Hope some of this helps!

Hello  ,

I need guidance for OTC drug product ,having already available OTC monograph.

What are manufacturing criteria and documents we need to prepare for inspection ?

How we design specification if we consider oral tablet dosage form?

Is there any specific guidance for stability study for OTC monograph product?

Regards,

Sapna

Dear Experts,

Thank you for your valuable input on the topics.

Would you please clarify below points (when product is available in final OTC monograph),

• Does it required to prepare a eCTD for OTC? what are the modules applicable/ not applicable for OTC?
• What will be the submission gateway?
• Does it required to take any number like NDA/ANDA?
• Is the there any fees involvement with OTC submission?
• When we can start marketing? immediately after submission and Drug listing or we have to wait for certain period?
• Does a GDUFA listed facility have to pay any additional fees?

I am looking for a complete guidance for OTC submission to USFDA.

Hi Sapna.

First rule - OTC are drugs just like any other prescription product.  Therefore, all of the general requirements for drug products attach to OTC products as well.  So you would handle this in exactly the same manner as you would handle production of any other oral tablet dosage form that would require a healthcare provider's prior approval/prescription to obtain.  Also, regarding FDA, they have the same requirements for documentation and stability as the agency would expect for any other type of drug product.  It is a misunderstanding (potentially significant from a regulatory perspective) to believe that the FDA will allow OTC products to avoid things that other manufacturers of drug products must comply with.  The only difference between OTC monograph drugs and any other drug product on the market is the elimination of the pre-approval of the FDA to market these drugs.

More importantly, this allowance only applies to products compliant to the monograph in formula (active ingredient, levels and allowable combinations), dosage form (if FDA specifies that the allowed dosage forms are liquids and tablets but you decide to create a powder the FDA could consider your product a "new drug" if you don't go through the full FDA pre-approval process!) and labeling (if you change the labeling of any required statement noted within quotation marks on the monograph you are asking to have an issues with the FDA.  While truthful and non-misleading statements are allowed (it states this in just about every monograph I have ever read!) it is also still a little risky to include any statements in the label that do not come from the monograph because whether a statement is "truthful and not misleading" can be debated depending on the presentation and exact language of the statement.

For specifications I would start with the applicable chapter in the USP for tablet dosage forms.  This is a simple way to ensure that you are doing at least enough testing to provide FDA with an understanding that you take your product and your responsibility as a manufacturer seriously.  Generally I would look to things like dissolution time, homogeneity of the powder and the tablets themselves, hardness, if time release then checking the consistency of the release across time, etc.  This is in addition to the fairly standard "color, appearance, scoring, marking" requirements that would be significant.

Hope some of this helps!

Hello  ,

I need guidance for OTC drug product ,having already available OTC monograph.

What are manufacturing criteria and documents we need to prepare for inspection ?

How we design specification if we consider oral tablet dosage form?

Is there any specific guidance for stability study for OTC monograph product?

Regards,

Sapna

Hi Sujan.

You will not necessarily need to complete a full eCTD for OTC.  It is possible to do your drug listing via CDERDirect and it is a bit simpler as well.  The CDERDirect system allows you to enter the information you need to enter and then the system validates your information to ensure that the necessary information is complete and available.  Also, with this system I have gotten acceptance within 1-2 hours of uploading the full data set to the system so it is a very responsive system and will also help to guide you in what is required or not.

If the OTC is monograph and it complies with the monograph requirements you will not need any NDA/ANDA numbers because the product is legally marketed without an approved application.  In fact this is the entire purpose of the OTC system in the US - to avoid unnecessary review and approval of hundreds of applications that effectively would have almost identical data.  These products in the OTC space have been determined by USFDA to meet the following criteria:

1. The condition is amenable to self-diagnosis and self-selection of treatment options by non-healthcare personnel
2. The safety of the active ingredients has shown to have a significant benefit to risk ratio and have been safely used for the treatment of such condition
3. It is possible for a layperson without medical training or professional oversight to read, understand and apply the directions appropriately as written in order to ensure safe use of the product to treat the condition.

Currently there are no direct fees associated with OTC products unless you fit into one of the requirements under ODUFA that was passed a couple of years ago.  Much of these requirements for fees tend to be on the establishment registration side or on the citizen's petition to update a monograph in some way.

Once an OTC product is added to your drug listing you may immediately begin marketing the product.  There is no waiting period required by the regulation.  However, I would generally recommend that you not begin importing product into the US until after your drug listing has been updated.  This is to avoid the situation where your product reaches port in the US before you have finished your drug listing and then having to provide FDA with the NDC number for the product which will only be visible to the field offices once that drug listing process has been completed.

As for whether or not a GDUFA facility would be required to pay the establishment fees - that I am not entirely certain of.  I would have to leave that either to other experts who have been in that situation or you might choose to contact FDA directly to understand the question.  I also see that someone else has added several good links to FDA's website which might provide additional context around this particular question.

Dear Experts,

Thank you for your valuable input on the topics.

Would you please clarify below points (when product is available in final OTC monograph),

• Does it required to prepare a eCTD for OTC? what are the modules applicable/ not applicable for OTC?
• What will be the submission gateway?
• Does it required to take any number like NDA/ANDA?
• Is the there any fees involvement with OTC submission?
• When we can start marketing? immediately after submission and Drug listing or we have to wait for certain period?
• Does a GDUFA listed facility have to pay any additional fees?

I am looking for a complete guidance for OTC submission to USFDA.

Hi Sapna.

First rule - OTC are drugs just like any other prescription product.  Therefore, all of the general requirements for drug products attach to OTC products as well.  So you would handle this in exactly the same manner as you would handle production of any other oral tablet dosage form that would require a healthcare provider's prior approval/prescription to obtain.  Also, regarding FDA, they have the same requirements for documentation and stability as the agency would expect for any other type of drug product.  It is a misunderstanding (potentially significant from a regulatory perspective) to believe that the FDA will allow OTC products to avoid things that other manufacturers of drug products must comply with.  The only difference between OTC monograph drugs and any other drug product on the market is the elimination of the pre-approval of the FDA to market these drugs.

More importantly, this allowance only applies to products compliant to the monograph in formula (active ingredient, levels and allowable combinations), dosage form (if FDA specifies that the allowed dosage forms are liquids and tablets but you decide to create a powder the FDA could consider your product a "new drug" if you don't go through the full FDA pre-approval process!) and labeling (if you change the labeling of any required statement noted within quotation marks on the monograph you are asking to have an issues with the FDA.  While truthful and non-misleading statements are allowed (it states this in just about every monograph I have ever read!) it is also still a little risky to include any statements in the label that do not come from the monograph because whether a statement is "truthful and not misleading" can be debated depending on the presentation and exact language of the statement.

For specifications I would start with the applicable chapter in the USP for tablet dosage forms.  This is a simple way to ensure that you are doing at least enough testing to provide FDA with an understanding that you take your product and your responsibility as a manufacturer seriously.  Generally I would look to things like dissolution time, homogeneity of the powder and the tablets themselves, hardness, if time release then checking the consistency of the release across time, etc.  This is in addition to the fairly standard "color, appearance, scoring, marking" requirements that would be significant.

Hope some of this helps!

Hello  ,

I need guidance for OTC drug product ,having already available OTC monograph.

What are manufacturing criteria and documents we need to prepare for inspection ?

How we design specification if we consider oral tablet dosage form?

Is there any specific guidance for stability study for OTC monograph product?

Regards,

Sapna