From Historical Precedent to Modern Approvals: Lessons Learned on OTC Drug Products for FDA OMORs

Over-the-Counter (OTC) drug monographs play a pivotal role in ensuring OTC drug products meet safety, efficacy, and quality standards while reducing barriers to commercialization. The OTC Monograph Order Request (OMOR) is a process that combines regulatory compliance with operational efficiency and functions outside traditional drug approval pathways like an NDA or BLA.

By examining the evolution of regulations and processes within the FDA’s oversight of OTC drugs, we can glean valuable information from historical precedents and modern approvals to apply lessons learned to regulatory strategy for modern products.

The Role of OMOR in FDA Oversight

OMORs refer to the systematic review and management of OTC monographs and thereby the marketing of OTC drug products. The OMOR process involves assessing the safety, efficacy, and quality of drug products to ensure that they meet established standards of GRASE (Generally Recognized as Safe and Effective) before reaching consumers.

The OMOR process includes evaluating clinical data, manufacturing practices, labeling accuracy, and adherence to regulatory requirements through the establishment of new OTC monographs or through innovation to existing OTC monographs.

Historical Precedents: A Look Back

To fully understand the evolution of Over-the-Counter Monograph Order Requests (OMORs) with the FDA, it’s important to examine the historical milestones that have shaped modern regulatory practices. The following key events highlight the development of FDA oversight and its impact on the OTC drug landscape:

1. Early Drug Regulations: The origins of FDA oversight can be traced back to the early 20th century with the passage of the Pure Food and Drug Act of 1906. This act aimed to prevent misbranding and adulteration of foods and drugs, setting a foundational precedent for regulatory oversight. In 1951, the Durham-Humphrey amendment defined the difference between prescription-only medications, which could have potentially dangerous side effects, and OTC drugs, which can be safely self-administered. Additional  early drug legislation, such as the Sherley Amendments of 1912, the Federal Food, Drug, and Cosmetic Act of 1938, the 1962 Kefauver-Harris amendment, and the DESI Program of 1966, introduced more rigorous standards and reviews for both prescription and OTC drug products. These early drug regulations laid the groundwork for modern OMOR practices.
2. The OTC Drug Review (1972): While these early drug regulations established standards for safety and efficacy of all drugs, a landmark moment in OTC drug regulation came with the FDA’s OTC Drug Review initiative beginning in 1972. This comprehensive review aimed to evaluate the safety and efficacy of OTC drugs that had been marketed prior to the 1938 Act. The process was groundbreaking in its systematic approach to categorizing OTC drug ingredients and setting monographs that guide the approval of new products. This review established a precedent for rigorous evaluation and has influenced subsequent OMOR practices.
3. The Drug Approval Modernization Act (1997): The FDA Modernization Act of 1997 marked a significant shift towards streamlining drug approval processes, including those for OTC products. It introduced provisions for accelerating approvals and improving transparency. This act highlighted the importance of adapting regulatory processes to meet the evolving needs of the pharmaceutical industry and paved the way for modern OMOR practices.
4. The CARES Act (2020): Under the CARES Act of 2020, along with a Goals Letter negotiated between industry and the FDA, established a new process for OTC drug review as well as the requirements and timelines for that review. This new process involves an Administrative Order Process that allows the Agency or industry to initiate an OMOR in order to update existing active ingredient’s GRASE status or to introduce new active ingredients to the OTC drug market. This Administrative Order Process included pathways for exclusivity, OTC-specific meetings, and a user fee system to fund activities related to OTC monograph drugs. 

Innovations in Modern OMOR Practices

The FDA’s modern approach to OMORs reflects a more sophisticated and inclusive regulatory framework. The following elements are central to this modernized approach:

1. Data-driven decision making: As part of the OMOR Format and Content Guidance, the Agency expects that written summaries of study results will not be sufficient to make a GRASE determination. Instead, the guidance repeatedly recommends providing complete datasets be included as part of the OMOR submission. While the guidance does not include a requirement for SEND or CDISC datasets, this increased focus on datasets highlights the FDA’s ongoing shift toward data-driven decision making. Historical precedents emphasize the importance of rigorous evaluation, but today’s data-driven approach enhances the precision and efficiency of Agency reviews.
2. Enhanced transparency: In an effort to build on historical lessons about transparency, the FDA aims to continuously improve communication with stakeholders throughout the entire Administrative Order process. There are multiple checkpoints which allow for manufacturers, consumers, and the Agency to have an open dialogue which aims to foster trust and can be used to address potential issues early in the process.
3. Risk-based approach: Risk assessment methodologies in modern OMORs will be used to consider factors such as usage patterns, population subgroup analysis, and emerging real world safety data. This new approach moves away from broad safety and efficacy criteria and instead reflects an approval process that is both adaptable and comprehensive.
4. Public involvement: Public comment periods and increased stakeholder engagement represent an inclusive approach to the Administrative Order process. This approach helps highlight diverse perspectives and enhances the quality of the entire OTC Monograph update process.

Lessons for the Future

The FDA’s approach to OMORs offers important lessons for the future of regulatory oversight. As the landscape continues to evolve, the following lessons will help ensure that the regulatory process remains focused on the needs of both the industry and consumers:

1. Adaptability & Innovation: The ongoing evolution of the FDA OTC review and approval process demonstrates the need for a process that is adaptable and efficient. As new challenges and technologies continue to develop, the Agency must remain flexible and be willing to embrace innovation from the industry in order to maintain regulatory relevance and operational efficiency.
2. Continuous Improvement: The ongoing refinement of OMOR practices highlight the importance of continuous improvement in the regulatory space. A nimble, transparent regulatory review process is necessary to ensure adequate safety and efficacy without limiting access to OTC drug products. Future enhancements to the OTC Monograph process should foster innovation, increase transparency, and account for both industry and consumer feedback.  
3. Balancing Regulations & Access: Maintaining accessibility for consumers to OTC drugs that are safe and efficacious is a delicate balance. Historical precedent and modern practices emphasize the need for this balance. Future improvements in the OMOR process should continue to strive to maintain and improve this balance.

The evolution of FDA OTC has shaped the current OMOR process and OTC Monograph reform. By exploring how past experiences have influenced current practice, one can better understand how the current regulatory approach was defined. By evaluating historical decision making and leaning into innovation, the FDA can ensure the safety, efficacy, and quality of OTC drug products which will in turn benefit consumers and advance public health overall.

Schedule a meeting with MMS regulatory industry experts today to help your team navigate the OMOR process and communicate with health authorities on your OTC drug products.

Authored by: Ritchie Patton, Manager, Regulatory Strategy.