7 Legal Keys to Getting Your OTC Drug to Market

So you have an OTC drug and you want to get to market but don’t know how.

If you’re in the OTC drug market, you’re probably fairly sophisticated.  You probably already know that your product is not:

• A cosmetic
• A dietary supplement
• A medical food
• An Rx drug or homeopathic drug

You have an OTC drug because your product claims to prevent, treat, mitigate, or cure a disease, plain and simple, and the active ingredient and the labeling conforms to an OTC monograph.

This is a good start.  Here are 3 other key things you need to know to get your OTC product to market.

Key # 1: Understand the FDA Regulatory Basics of the OTC Drug Pathway

An OTC drug is generally recognized as safe and effective and is not misbranded if it meets each of the conditions contained 21 CFR Part 330 (Over-The-Counter (OTC) Human Drugs Which Are Generally Recognized as Safe and Effective and Not Misbranded) and each of the conditions contained in any applicable monograph.

21 CFR 330.1 outlines the general conditions for general recognition as safe, effective and not misbranded.  These include:

• Manufacturing: The product is manufactured in compliance with current good manufacturing practices.
• Registration and Listing: The establishment in which the drug product is manufactured, is registered, and the drug product is listed, according to FDA rules.
• Labeling: The product is properly labeled. This includes essentially limiting claims to the indications of use that have been established in the applicable OTC drug monograph.

Or, according to Section 330.1(c)(1): “alternative truthful and nonmisleading statements describing only those indications for use that have been established in an applicable monograph, subject to the provisions of section 502 of the act relating to misbranding and the prohibition in section 301(d) of the act against the introduction or delivery for introduction into interstate commerce of unapproved new drugs in violation of section 505(a) of the act.”

As well, the advertising prescribes, recommends, or suggests the product’s use only under the conditions stated in the labeling.

The labeling must contain various warnings stated in the regulations (Section 330.1(g)); follow the rules governing dosage (330.1(h)); follow rules governing use of terms such as “for relief of” (and many other defined terms) (330.1(i)); and follow other language requirements (such as with respect to deleting, “in case of”) (330.1(j)).

• Active Ingredients: The product contains “only suitable inactive ingredients which are safe in the amounts administered and do not interfere with the effectiveness of the preparation or with suitable tests or assays to determine if the product meets its professed standards of identity, strength, quality, and purity. Color additives may be used” only in accordance with law.
• Container: The product container and container components meet applicable legal requirements.

There are additional requirements, such as specific rules for a pregnancy-nursing warning as applicable (330.2); and, a requirement to imprint an identification code on solid oral dosage form drug products (330.3).

Key # 2: Figure out Whether Your Product Conforms to an Existing OTC Monograph

Unlike the new drug application (NDA) process, the OTC monograph process generally does not require clinical studies.

In Differences: NDA Process and OTC Monograph Process, FDA notes: “Label comprehension and actual use studies are not required for ingredients already covered by a final or tentative final monograph.”

Regarding the OTC route, FDA explains in training materials that the monograph is:

a kind of “rule book” of conditions for each therapeutic category covering acceptable ingredients, uses (indications), doses, formulations, labeling, and testing.

A drug marketed that is consistent with the conditions set forth under a final monograph and all other general applicable OTC requirements is considered generally recognized as safe and effective for the uses set forth under the monograph.

Put another way:

The monographs establish conditions under which certain OTC drug products are generally recognized as safe and effective. Products containing active ingredients or indications that are nonmonograph require an approved New Drug Application for marketing.

(OTC Process). As FDA notes in OTC (Nonprescription Drugs):

If a drug cannot comply with the drug monograph, an IND and approved NDA is necessary before the drug product may be marketed.

There are procedures for a citizens’ petition to amend an existing monograph, or to establish new monographs.  However, before going there, first understand the therapeutic categories by which FDA organizes the list of OTC drugs.

Key # 3: Review the Therapeutic Categories of OTC Drugs

FDA organizes its OTC rulemakings by therapeutic category subtopics on its page, Status of OTC Rulemakings. While this page “is intended as a research aid and is not an official FDA record,” it is good initial guide to see whether a therapeutic condition has an OTC monograph where treatment of that condition is the indication for use.

Below are some sample categories that might potentially be relevant to treatment of a skincare OTC product.  We have not researched all of these categories, nor have we read any monographs in detail.

• Analgesic, External or External Analgesic
• Callus Remover
• Corn Remover
• Seborrheic Dermatitis
• Skin Protectant
• Topical Analgesic
• Wart Remover

An omission from the list of therapeutic categories is a good sign that an indication for use relating to treatment of a particular condition would not conform to an existing monograph.

Key # 4: Understand the non-OTC, Rx Drug Regulatory Pathways

To market a product for any condition on the list of OTC therapeutic categories where the product does not conform to an OTC monograph, a company’s likely choices would be:

• To file a 505(b)(1) NDA (containing full reports of investigations of safety and effectiveness).
• To file a 505(b)(2) NDA (permits FDA to rely on a previous finding of safety and effectiveness that led to approval of an NDA or on data not developed by the applicant such as published literature). This pathway could be appropriate, for example, if the new product has the same active ingredient in a FDA-approved drug but the dosage or form is different.
• To change the indication of use and find a suitable monograph. (To that end, see our brief discussion in Section C. below, Possible Claims/Indications for Use).
• Submit a citizens’ petition to amend an existing monograph, or propose a new monograph. (As a starting point, see 21 CFR 330.10 (Procedures for classifying OTC drugs as generally recognized as safe and effective and not misbranded, and for establishing monographs).

FDA says in one of its guidance documents:

An NDA can be used to request approval of an OTC drug that deviates in any respect from a monograph that has become final (see 21CFR 330.11).

In other words, if the company proposes to deviate from a monograph (for example, with respect to active ingredient, intended use, etc.) then the route to market is via an NDA.

Key #5 – Review Proposed ingredients in light of possible OTC monographs

FDA explains in its Over-the-Counter (OTC) Monograph Process that FDA classifies OTC ingredients into three panels:

• Category I: generally recognized as safe and effective for the claimed therapeutic indication;
• Category II: not generally recognized as safe and effective or unacceptable indications;
• Category III: insufficient data available to permit final classification

Ingredients are searchable through the FDA list of OTC Active Ingredients (April 7, 2010). However, there’s a bit of legal “secret sauce” in the search, because this will require checking various regulatory sources and going back and forth to figure out whether the ingredients themselves take the product out of possible OTC status.

Key # 6 – Review Possible claims/indication(s) for use

The key here is to review the claims or indications for use a company is proposing against the FTC therapeutic category.

Again, this requires some legal secret sauce in that the search process can seem rather byzantine and convoluted to the outsider.  It’s a legal treasure hunt – an exciting (to the lawyer) foray into the rules as they are placed in different parts of the regulatory code.

An FDA lawyer will search, among other places, the language of the Final Monograph for a particular therapeutic category (such as “skin protectant drug product”); and then check this against the claim or claims the company intends to make.

For example—a skin protectant drug product is defined as:

A drug product that temporarily protects injured or exposed skin or mucous membrane surfaces from harmful or annoying stimuli, and may help provide relief to such surfaces.

The rules set out specific active ingredients, and then there are different kinds of active ingredients and also different combinations.

It is unfortunately easy for a company at the beginning stages of this process to make many claims—too many claims—for this product, and thus easily run outside the boundaries of the indications for use that are allowed under a particular monograph.

Key #7 – Decide Whether the Product can Be Reformulated

We said at the beginning that the savvy healthcare entrepreneur in the OTC drug market probably has already ruled out making their product:

• A cosmetic
• A dietary supplement
• A product that would fall into another regulatory category

Nonetheless, depending on the answers to the first 6 keys, it may be worth thinking about reformulating the product so as to try to get it into a different regulatory category.

Sometimes depending on the formulation, a company can go back and forth between the OTC drug and Cosmetics category, for example.

On the other hand, if the company is well bankrolled and wants to go for the NDA, that would be the option.

As yet another possibility, a creative FDA attorney might look at other potential therapeutic categories that the company has not yet considered, and assess whether these might fit the product.

This requires experience, judgment, savvy, and an eye for market conditions.

A dull, plodding approach won’t cut it, no matter whether the lawyer was Order of the Coif or showered with some other award.  In today’s fast market, you have to be nimble.

The FDA attorney and key company executives might look to:

• Change up the active ingredient so as to fit the monograph
• Think further through non-monograph ingredients
• Modify the product claims
• Look to reformulate to fit a different regulatory classification.

See our prior post:

Bottom Line

OTC drugs seem straightforward at first in that the magic wand is conforming to a monograph.  In the real world, though, this isn’t always possible.

Contact an OTC drug law FDA attorney who is expert in OTC drug companies and the unique FDA issues they face.