Finding GRASEland: Navigating the New Regulatory Path for Grandfathered OTC Drugs 

As part of the Over-the-counter (OTC) Monograph reform that was initiated as part of the 2020 CARES Act, the FDA affirmed the GRASE conditions for certain OTC therapeutic drug classes by establishing 32 OTC Monographs. Some OTC drugs and drug classes had not yet met the regulatory burden to receive a deemed final order which would have established their OTC Monographs; these drugs that previously fell under specific categories with a Tentative Final Monograph (TFM) or Advanced Notice of Proposed Rulemaking (ANPR) have a unique regulatory history and complex pathway ahead. These drugs were part of a legacy system and have been “grandfathered” into the market unless and until the FDA issues a ‘not GRASE’ final order which would force these drugs off of store shelves. For manufacturers, navigating this new OTC landscape—particularly for those still marketing products under TFM or ANPR status—poses challenges. As a leading CRO, MMS Holdings offers critical support in helping companies assess the necessity to file an OTC Monograph Order Request (OMOR) to secure GRASE designation, understand their readiness to respond to an Agency Initiated Order, and build a comprehensive regulatory strategy to get Agency alignment early. 

Understanding TFM and ANPR Drugs 

The FDA’s OTC Drug Review, established in 1972, aimed to review and classify OTC drugs based on their safety and effectiveness. The review process created monographs—detailed regulations covering active ingredients, labeling, and usage guidelines for OTC drugs that were deemed GRASE. You can read more about the regulatory history of OTC products here. (Link to OTC Overview Blog) 

The FDA’s OTC Drug Review was established to assess the safety and effectiveness of OTC drugs already on the market. With this review, OTC products were not required to be evaluated under the New Drug Application or NDA process but instead were part of a multistep process which saw drugs go from ANPR to TFM to Final Monograph. The TFM represents a proposed monograph for a drug category, while ANPR is an earlier stage where the FDA is still collecting data. The ANPR and TFM designations had three categories to label their ongoing assessment status: GRASE, not GRASE, or Insufficient data or Category I, II, or III, respectively.  

While drugs with a Category I TFM were designated as GRASE through Deemed Final Orders, Category III TFM and Category I ANPR drugs did not receive their GRASE designation but have been allowed to stay on the market awaiting a final ruling on GRASE designation. Some drug classes have remained in TFM or ANPR status for decades, leaving OTC drug manufacturers in regulatory limbo. Without a finalized monograph, these drugs are not fully recognized as GRASE, leaving companies vulnerable to enforcement actions or market disruptions if safety concerns arise. 

Pre-CARES Act Category
ANPR Cat I
ANPR Cat II
ANPR Cat III
TFM Cat I
TFM Cat II
TFM Cat III
FM

Post-CARES Act Category
GRASE designation received; Deemed Final Order; OTC Monograph established
GRASE designation not finalized; may continue to be marketed pending administrative order Not
GRASE; cannot continue to be marketed

Transition of OTC Drug Categories Pre-CARES Act to Post-CARES Act

Post-CARES Act Category	Pre-CARES Act Category
GRASE	TFM Cat I, FM
Pending	ANPR Cat I, TFM Cat III
Not GRASE	ANPR Cat II, TFM Cat II

How MMS Holdings Can Help with OMOR Filings 

The CARES Act of 2020 reformed the OTC drug monograph process, offering a streamlined pathway for manufacturers to secure GRASE status through the OMOR process. An OMOR allows companies to request modifications to the monograph, including the addition of new ingredients, labeling updates, or shifting from TFM/ANPR status to full GRASE designation. 

MMS Holdings specializes in regulatory strategy and submissions, helping companies navigate the complexities of filing an OMOR. Our experience includes: 

• Data Collection and Analysis: We assist in gathering and analyzing the necessary clinical, non-clinical, and historical data to support the safety and efficacy of your product. 

• Regulatory Expertise: MMS has extensive experience with FDA regulatory pathways and can provide strategic guidance for preparing a successful, timely OMOR submission. 

• FDA Meeting Support: We can help you prepare your team for and participate in FDA interactions including Type X, Y, and Z meetings. You can read more about FDA meetings for Over-the-Counter Monograph Drugs here. (Link to OTC Meetings Blog) 

Moving from TFM/ANPR to GRASE 

While the decision to submit a GRASE OMOR is not a one size fits all answer, by transitioning from a tentative or proposed status to full GRASE designation, companies can achieve regulatory certainty and reduce their risk of enforcement action. This transition also allows greater flexibility in marketing and product claims, enabling competitive positioning in the OTC space through Innovation OMORs. A final monograph also allows OTC drug manufacturers to make minor changes in dosage forms without prior notice to the FDA. MMS Holdings can assist you in making this strategic assessment and guide you through the OMOR process, ensuring that your products meet the necessary regulatory standards while maintaining compliance with FDA guidelines. 

This article was written by Ritchie Patton, Manager, Regulatory Strategy, Regulatory Affairs