Description
The Food and Drug Administration (FDA) has prepared this guidance in accordance with section 212 of the Small Business Regulatory Enforcement Fairness Act. It is intended to help small businesses better understand the new over-the-counter (OTC) labeling requirements set forth in 21 CFR 201.66 and prepare new labeling. Additional information is available in the guidance for industry Labeling OTC Human Drug Products Questions and Answers.2
Scope & Applicability
Product Classes
6Over-the-counter drug products for human use; The primary scope of the labeling guidance.
Nonprescription drug products subject to the monograph system.
Products with both drug and cosmetic attributes like sunscreens; Products that are both drugs and cosmetics; Products with both drug and cosmetic ingredients
Products combining drug, device, or biological constituents; Generally recommended for Enhanced Documentation; Requires 14971-based framework incorporating ICH Q9; A drug-device combination where the device constituent part detects ingestion.
Guidance provides a framework for over-the-counter drug products.
products that are both drugs and cosmetics
Stakeholders
4Target audience for the compliance guide
Entity required to conduct postmarket surveillance; entity responsible for submitting postmarket surveillance plans; Entity holding the approved PMA, HDE, or cleared 510(k); The entity responsible for conducting postmarket surveillance and submitting reports.; Entity that can use the checklist as a reference for submissions.
Entity involved in investigational drug supply chain
Entity required to maintain records of lot numbers for food released; Entity required to establish and maintain records under subpart J.
Regulatory Context
Attributes
6Format requirements for labeling
Information included under 'Other information'
Requirement for the physical appearance of calorie declarations; must be at least 50 percent of the size of the largest printed matter; The font size of calorie declarations, which must meet specific minimums.
Format used when Drug Facts content requires more than 60 percent of surface area
The unit of measure for oral dosage forms (e.g., tablet, teaspoonful).
feature of drug product package to protect consumers
Identified Hazards
Hazards
1A safety risk requiring specific warning language on the label.
Related CFR Sections (9)
- 21CFR201.66§ 201.66 Format and content requirements for over-the-counter (OTC) drug product labeling.
(a) Scope. This section sets forth the content and format requirements for the labeling of all OTC drug products. Where an OTC drug product is the subject of an applicable monograph or regulation that contains content and format requirements that conflict with this section, the content and format reRead full regulation →
- 21CFR201.21§ 201.21 Declaration of presence of phenylalanine as a component of aspartame in over-the-counter and prescription drugs for human use.
(a) Aspartame is the methylester of a dipeptide composed of two amino acids, phenylalanine and aspartic acid. When these two amino acids are so combined to form aspartame (1-methyl N -L-α-aspartyl-L-phenylalanine), they produce an intensely sweet-tasting substance, approximately 180 times as sweet aRead full regulation →
- 21CFR201.64§ 201.64 Sodium labeling.
(a) The labeling of over-the-counter (OTC) drug products intended for oral ingestion shall contain the sodium content per dosage unit (e.g., tablet, teaspoonful) if the sodium content of a single maximum recommended dose of the product (which may be one or more dosage units) is 5 milligrams or more.Read full regulation →
- 21CFR330.1§ 330.1 General conditions for general recognition as safe, effective and not misbranded.
An over-the-counter (OTC) drug listed in this subchapter is generally recognized as safe and effective and is not misbranded if it meets each of the conditions contained in this part and each of the conditions contained in any applicable monograph. Any product which fails to conform to each of the cRead full regulation →
- 21CFR201.307§ 201.307 Sodium phosphates; package size limitation, warnings, and directions for over-the-counter sale.
(a) Reports in the medical literature and data accumulated by the Food and Drug Administration indicate that multiple container sizes of sodium phosphates oral solution available in the marketplace have caused consumer confusion and appear to have been involved in several consumer deaths. Sodium phoRead full regulation →
- 21CFR347.50§ 347.50 Labeling of skin protectant drug products.
A skin protectant drug product may have more than one labeled use and labeling appropriate to different uses may be combined to eliminate duplicative words or phrases as long as the labeling is clear and understandable. When the labeling of the product contains more than one labeled use, the approprRead full regulation →
- 21CFR201.63§ 201.63 Pregnancy/breast-feeding warning.
(a) The labeling for all over-the-counter (OTC) drug products that are intended for systemic absorption, unless specifically exempted, shall contain a general warning under the heading “Warning” (or “Warnings” if it appears with additional warning statements) as follows: “If pregnant or breast-feediRead full regulation →
- 21CFR211.132§ 211.132 Tamper-evident packaging requirements for over-the-counter (OTC) human drug products.
(a) General. The Food and Drug Administration has the authority under the Federal Food, Drug, and Cosmetic Act (the act) to establish a uniform national requirement for tamper-evident packaging of OTC drug products that will improve the security of OTC drug packaging and help assure the safety and eRead full regulation →
- 21CFR701.3§ 701.3 Designation of ingredients.
(a) The label on each package of a cosmetic shall bear a declaration of the name of each ingredient in descending order of predominance, except that fragrance or flavor may be listed as fragrance or flavor. An ingredient which is both fragrance and flavor shall be designated by each of the functionsRead full regulation →
Related Warning Letters (10)
- 2025-12-23
CGMP/Finished Pharmaceuticals/Adulterated
SV Labs Corporation
- 2025-12-23
CGMP/Finished Pharmaceuticals/Adulterated
Guangdong Renhe Guozhuang Biotechnology Co., Ltd.
- 2025-12-23
CGMP/Finished Pharmaceuticals/Adulterated
Medinatura New Mexico, Inc.
- 2025-12-16
CGMP/Finished Pharmaceuticals/Adulterated
Sklar Personal Care Inc.
- 2025-12-16
CGMP/Deviations/Biologics License Application (BLA)
Microvascular Tissue, Inc.
- 2025-12-11
CGMP/Finished Pharmaceuticals/Adulterated
Catalent Indiana, LLC
- 2025-12-09
CGMP/Finished Pharmaceuticals/Adulterated
DeVere Manufacturing Inc.
- 2025-12-09
CGMP/Finished Pharmaceuticals/Adulterated
CDL Services, Inc. DBA Technichem
- 2025-12-09
CGMP/Finished Pharmaceuticals/Adulterated
Seaway Pharma Inc.
- 2025-12-02
Compounding Pharmacy/Adulterated Drug Products
PQ Pharmacy, LLC
See Also (8)
- Topical Acne Drug Products for Over-the-Counter Human Use--Revision of Labeling and Classification of Benzoyl Peroxide as Safe and Effective: Guidance for Industry (Status: Final)
- Labeling for Bronchodilators: Cold, Cough, Allergy, Bronchodilator, And Antiasthmatic Drug Products for Over-the-Counter Human Use (Small Entity Compliance Guide): Guidance for Industry (Status: Final)
- Labeling and Effectiveness Testing: Sunscreen Drug Products for Over-The-Counter Human Use — Small Entity Compliance Guide: Guidance for Industry (Status: Final)
- Labeling OTC Human Drug Products Using a Column Format (Status: Final)
- Labeling OTC Human Drug Products Updating Labeling in RLDs and ANDAs (Status: Final)
- Communications From Firms to Health Care Providers Regarding Scientific Information on Unapproved Uses of Approved/Cleared Medical Products: Questions and Answers (Status: Final)
- Assessing User Fees Under the Over-the-Counter Monograph Drug User Fee Program (Status: Draft)
- Child-Resistant Packaging Statements in Drug Product Labeling Guidance for Industry (Status: Final)