FDA Regulations for Over-the-Counter (OTC) Human Drugs: A Comprehensive Overview

Over-the-counter (OTC) human drugs are widely available on the shelves of pharmacies, grocery stores, and other retail locations across the U.S. These drugs are easily accessible to consumers because they do not require a prescription from a healthcare provider. While the FDA regulates both prescription and OTC drugs, there are key differences in how these products are managed. One significant distinction is that OTC drugs can often be marketed using an OTC Drug Monograph, which allows for commercialization without further FDA approval, provided the drug meets the monograph’s criteria.

Drug Establishment Registration

Any establishment involved in the manufacturing, repacking, relabeling, or salvaging of drug products intended for commercial distribution must register with the FDA, unless exempt. This requirement helps the FDA track which facilities are producing drugs either domestically or for import into the U.S.

For U.S.-based establishments, registration involves providing details such as the facility’s DUNS number, the manufacturing address, and contact information. Non-U.S. establishments must also include information about their U.S. Contact and Importer(s). Registration must occur within five days of introducing a drug product to the market. Once registered, the FDA assigns the establishment an FDA Establishment Identification (FEI) number, and the site becomes subject to inspection.

Establishments are required to renew their registration annually between October 1st and December 31st. This update should reflect any changes in contact information, company name, or establishment address. If no updates are needed, a No Change Notification must be submitted. Additionally, establishments must update their registration when there are changes to importer details or when new importers are added.

Product Listing

Most registered drug establishments must list all of their drug products to inform the FDA about the products in commercial distribution, including the manufacturer and distributor details. Each product must be assigned a National Drug Code (NDC) number, and the listing must include labeling in Structured Product Labeling (SPL) format.

Certain establishments, such as contract testing laboratories and those involved in specific types of medicated feeds, may be exempt from listing requirements. However, when changes occur—such as a change in company name or artwork that does not require a new NDC—listings must be updated accordingly. Additionally, product listings must be verified annually between October 1st and December 31st. If there are no changes, a Blanket No Change Certification must be submitted.

Marketing Regulations

OTC drugs must adhere to standards for safety, effectiveness, and current good manufacturing practices (cGMPs). They must also comply with FDA labeling requirements. These products can be regulated under an OTC Drug Monograph or through a New Drug Application (NDA).

OTC Drug Monographs

OTC Drug Monographs provide a framework for acceptable ingredients, dosages, formulations, and labeling requirements for OTC drugs. If a drug conforms to an existing monograph, it can be marketed without further FDA approval, as it is considered "generally recognized as safe and effective" (GRASE).

New Drug Applications (NDA)

If an OTC drug does not meet the criteria of an existing monograph, the manufacturer must submit an NDA or an Abbreviated New Drug Application (ANDA) for FDA approval before the product can be marketed. OTC drugs can either be marketed directly as nonprescription drugs or can transition from prescription to nonprescription status through FDA approval.

Proposed Rule

The FDA has proposed a new rule that could provide more flexibility for developing and marketing nonprescription drugs. The proposed rule introduces the concept of an Additional Condition for Nonprescription Use (ACNU). This would allow a drug application to propose conditions under which a product could be safely used without a prescription, even if labeling alone is not sufficient. Consumers would need to meet the ACNU criteria to purchase the product without a prescription.