Nonprescription OTC Drug Development

The most frequent inquiries PDG receives from prospective entrants to the OTC market relate to establishment registration/product listing, NDC and Drug Facts Labeling. While it is not quite that simple, the OTC marketplace still represents amazing opportunity based on lower barriers to entry relative to prescription drug products.

As you embark upon your OTC drug development program, PDG will first help you determine the regulatory status of your proposed drug product. There is always the possibility that the product may not be generally recognized as safe and effective (GRASE). On the other hand, it may be the subject of a Tentative Final Monograph (TFM), Final Monograph (FM), or even a New Drug Application (NDA). The next step will be to determine how your operation will fit into FDA’s regulatory framework (e.g. manufacturer, repacker, relabeler). This will determine how your establishment is registered and your product is listed.

If you are not a manufacturer, we can preliminarily address registration, listing and labeling as we help you source and qualify a manufacturer. Keep in mind that there are a number of FDA requirements for GMP compliant manufacturing and safety surveillance for which you will be responsible. PDG will help you with these, including development of quality systems such that you may be reasonably assured of regulatory compliance.

OTC or nonprescription drugs are those that can be labeled in such a way that the consumer can self-diagnose, self-treat, and self-manage the condition, with none of the parameters that define a prescription drug being present. On the other hand, if a drug is not safe for use except under supervision of a licensed practitioner because of potential toxicity or other harmful effects it will be regulated as a prescription drug.

A prescription drug may be switched to OTC (nonprescription) using a New Drug Application (NDA; including 505(b)(2)), NDA Supplement, or a Citizen Petition. It should also be noted that ANDAs may be filed, using the innovator’s NDA as the reference listed drug (RLD).

There are three types of Rx-to-OTC switches: full switch, partial switch or Direct-to-OTC. PDG will help you determine which is best to suit your needs. Not surprisingly, in the case of NDA development, FDA strongly encourages sponsors to request formal meetings throughout the process (e.g., Pre-IND, End of Phase 2, Pre-NDA). While clinical data may be relatively easy to come by, don’t be surprised by OTC consumer study requirements such as label comprehension (understanding the key label message), self-selection (choosing the right product), actual use (using according to labeled directions), or human factors (interacting with the product).

Anyone considering an Rx-to-OTC switch will also need expertise in the retail market. Neither this, nor the potential of consumer study requirements should prevent your firm from considering entry into the nonprescription marketplace. Because of our multiple contacts in the OTC market and experience placing consumer studies, PDG is well positioned to help you access all needed resources and expertise.

There are three great reasons to consider an Rx-to-OTC switch:

First, PDG has extensive experience with the various regulatory pathways, meetings with FDA, placing OTC consumer studies AND because of our previous work, we can connect you with potential partners who know the retail space.

Second, the opportunity is massive and growing. Over 240 million Americans use nonprescription drugs. When nicotine replacement therapies switched to OTC, sales nearly doubled the first year. While Rx-to-OTC switches continue to grow in popularity, a multitude of untapped opportunities remain.

Third, FDA is considering an expanded role for Rx-to-OTC switches through their Nonprescription Drug Safe Use Regulatory Expansion (NSURE). In fact, specific conditions have been identified as promising. These include chronic conditions like high blood pressure, high cholesterol, migraine headaches, and asthma management.

Other potential opportunities for further Rx-to-OTC development include antibiotics (topical), antidiabetics, antifungals, antihistamines, antismoking, corticosteroids, epinephrine injections, muscle relaxants, oral contraceptives, prescription prenatal vitamins, and triptans.

Other disorders that represent potential development opportunities include acne, benign prostatic hyperplasia/hypertrophy, coughs, colds, erectile dysfunction, eye infections, overactive bladder, and parasitic worm infestations.

The growth of the nonprescription market is projected to continue. Contributing factors are expected to include (among others) big pharma Rx-to-OTC switches and FDA’s encouragement of such switches. With this growth and change comes opportunity for drug firms of all sizes and positioning. This includes a number of sometimes overlooked methods for OTC manufacturers and marketers to expand product lines. Examples follow:

ANDAs – sometimes perceived as being for generic prescription drugs only, this is not the case. As the number of former prescription blockbusters entering the OTC market through NDAs grows, the opportunity to file ANDAs and develop generic versions of these drugs does as well. When one considers that the 2016 FDA PDUFA user fee to file an NDA is well in excess of $2 million, the 2016 generic user fee of $56,000 seems downright affordable in comparison. Given that NDA user fees grew at over 14% per year during their first 24 years, now may be the best time ever to file an ANDA to market a proven OTC drug. Another consideration for current OTC manufacturers considering such ANDAs is that GMP quality systems should already be in place, thus eliminating a (major) barrier to entry into the generic OTC market.

Combining OTC drugs with Class I or Class II medical devices – While the number of OTC drugs yet to be combined with Class I, II (or unclassified) medical devices cannot be measured, the possibilities are numerous. There are simply hundreds of each. Case in point: at one time there was no such thing as an occlusive bandage with pre-applied nonprescription topical antibiotic. The advantage of such combinations is that it may require only a 510(k), or no review at all. One of the first steps PDG will assist with is determination as to the regulatory status and applicable development pathway for your proposed combination product.

New Nonprescription Combinations – Combining OTC drugs may result in an enhanced nonprescription product (e.g. Gold Bond^® Medicated Pain and Itch Relief Cream with Lidocaine) or may lead to an opportunity to develop a new prescription drug. For example, prescription only pancrelipase (Creon^®) is comprised of three OTC Final Monograph digestive aids, amylase, lipase, and protease. Adding an OTC to a prescription drug to form a fixed dose combination product may result in a viable 505(b)(2) prescription drug candidate that has the ultimate potential of extended lifecycle through an Rx-to-OTC switch. The combination of OTC  benzoyl peroxide and prescription only adapalene was first approved as a prescription 505(b)(2) in 2008. In 2016 another 505(b)(2) for adapalene was approved, this time as an Rx-to-OTC switch. PDG has experience with, and can help you navigate, all such regulatory scenarios.

Change a Monograph – if a nonprescription (monograph) product can be improved through deviation from that monograph as currently written, don’t rule out the possibility. Citizen Petitions function (among others) to request that FDA amend a monograph at any phase including after publication of a final monograph, with certain limitations. PDG has written multiple Citizen Petitions and can help you. Generally speaking, you will need “data or information demonstrating that a product based on the proposed deviation is generally recognized among scientific experts as safe and effective.” If you are trying to introduce new OTC ingredients to the US market that have been marketed overseas, you may have a candidate for a Time & Extent Application (TEA). We can help you with this as well. 

Cite the Monograph in a 505(b)(2) – Also known as a monograph deviation, an NDA deviation is simply a 505(b)(2) that references a Final Monograph (FM). For example, the product might meet all the specifications of the FM except for the dosage form. Therefore, the FM would be used to support safety and effectiveness while new CMC information would be developed for submission to the NDA. Whether you are sure of the appropriate pathway or not, feel free to pick up the phone and run it by us.