There are two regulatory pathways to bring a nonprescription drug to market in the US -- the Drug Application process and Over-The-Counter (OTC) Drug Review (OTC Monograph) process.
In 1972, FDA established the OTC Drug Review to evaluate the safety and effectiveness of hundreds of thousands of OTC drug products that were on the market at that time. Under the OTC Drug Review, FDA regulates certain nonprescription drugs using a system that groups products by therapeutic category. For each category, FDA issues an OTC drug monograph (OTC monograph).
An OTC monograph is a “rule book” for each therapeutic category establishing conditions, such as active ingredients, uses (indications), doses, labeling, and testing, under which an OTC drug is generally recognized as safe and effective (GRASE) and can be marketed without a New Drug Application and FDA pre-market approval.
Nonprescription drug products marketed under the OTC Drug Review are referred to as OTC monograph drugs.
Prior to March 2020, an OTC monograph could only be added, removed, or changed by notice-and-comment rulemaking, a cumbersome three-phase public rulemaking process that resulted in FDA being unable to quickly make changes to OTC monographs even when addressing significant safety concerns.
On March 27, 2020, the President signed into law H.R. 748, “the Coronavirus Aid, Relief, and Economic Security Act” or the “CARES Act”. The law includes statutory provisions, which FDA refers to as OTC Monograph Reform, that reforms and modernizes the OTC monograph drug development and review process. The law replaces the rulemaking process with an administrative order process to add, remove, or change an OTC monograph. The administrative order process is expected to improve efficiency, timeliness and predictability in the OTC Drug Review process. The law also provides FDA with user fees to support OTC monograph drug activities.
Administrative Order Process
The administrative order process to add, remove, or change a monograph can be initiated by either industry (any person or group of persons marketing, manufacturing, processing, or developing a drug) or FDA.
Industry can request that FDA issue an administrative order by submitting an OTC monograph order request (OMOR) to FDA. FDA will determine if the OMOR is acceptable for filing. If FDA accepts the OMOR for filing, FDA will the review the OMOR and issue a proposed order. The public will receive at least 45 calendar days to submit comments on the proposed order. After reviewing and considering the comments, FDA will issue a final order which is the final OTC monograph. All final orders are subject to dispute resolution, an administrative hearing, and judicial review.
FDA issues a proposed order. The public will receive at least 45 calendar days to submit comments on the proposed order. After reviewing and considering the comments, FDA will issue a final order which is the final OTC monograph. All final orders are subject to dispute resolution, an administrative hearing, and judicial review.
Expedited Procedure for FDA-Initiated Order
FDA can initiate an expedited procedure for issuing an administrative order when:
- a drug poses an imminent hazard to public health; or
- a change in the labeling of a drug, class of drugs, or combination of drugs is reasonably expected to mitigate a significant or unreasonable risk of a serious adverse event associated with use of the drug
Under the expedited procedure, FDA issues an interim final order that becomes effective before the public has an opportunity to comment. After issuing the interim final order, the public will receive at least 45 calendar days to submit comments on the interim final order. FDA then issues a final order taking into account public comment.
Meet with FDA
FDA encourages all potential drug sponsors and requestors of OTC monograph drugs to examine the information available from FDA's website related to the OTC Drug Review process.
FDA is developing guidance regarding formal meetings between FDA and sponsors or requestors who intend to submit an OMOR. Prior to publication of that guidance, submit meeting requests to Monograph-Meeting-Requests@fda.hhs.gov.
For general question on the OTC Drug Review process, email email@example.com.
- Over-the-Counter (OTC) Drug Review | OTC Monograph Reform in the CARES Act
- Link to OCOMM Developed OTC Monograph Reform Webpage
- Historical Status of OTC Rulemakings
- Small Business Assistance: Frequently Asked Questions on the Regulatory Process of OTC Drugs