Description
This guidance provides recommendations regarding the use of restricted delivery systems , to limit unintentional ingestion of oral liquid drug products (e.g., oral solution, oral suspension) by children. The recommendations in this guidance apply broadly to oral liquid drug and biological products. , Accordingly, this guidance is intended for manufacturers of oral liquid drug and biological products. In this guidance, the term manufacturer is used broadly to include firms that market drug products under the Over-the-counter (OTC) Drug Review; holders of new drug applications (NDAs), biologics license applications (BLAs), and abbreviated new drug applications (ANDAs); and firms that manufacture components packaged or labeled for commercial distribution with oral liquid drug products, including firms that buy product in bulk to sell under their own label and add a flow restrictor to the product when they fill the bulk product into direct-to-consumer packaging.
Key Topics
Terms and concepts identified from this document
Scope & Applicability
Product Classes
1Subject of the guidance regarding restricted delivery systems; Products associated with unintentional ingestion risks in children.
Stakeholders
2Entity responsible for submitting NDINs
It may be a hardship for patients and/or caregivers to attend in-person; Individuals who may assist patients or provide observations when patients cannot self-report.; conducted with caregivers to obtain similar feedback
Regulatory Context
Regulatory Activities
5New Drug Application
Biologics License Application
Abbreviated New Drug Application
FDA process for clearing or approving devices for clinical use.
Regulatory process for over-the-counter drugs
Document Types
2Specific labeling format for OTC drugs.; required labeling format for OTC drug products
Additional packaging component for graphical instructions
Attributes
3Special packaging designed to be significantly difficult for children under 5 to open
Physicochemical characteristic used to assure product acceptability.
Products with this attribute are excluded from biowaivers
Technical Details
Substances
5Drug substance with specific flow restriction limits
Drug substance with specific flow restriction limits
Drug substance with specific flow restriction limits
Known or potential interferent for blood glucose measurement.; Listed as an example interferent in the recommended summary table format.
Drug substance with specific flow restriction limits
Testing Methods
2Recommended as part of the development program for restricted delivery systems.
Studies to optimize medical device and packaging design.
Identified Hazards
Hazards
4Accidental exposure of children to oral liquid drugs; Safety concern involving children younger than 6 years old.
Public health concern driving the need for flow restrictors
Risk associated with acetaminophen overdose
Risk if a restricted delivery system is easily removed or pushed into the bottle.
Standards & References
External Standards
2United States Pharmacopeia standard for Packaging and Storage Requirements.
Test Method for Assessing Non-Metered Restricted Delivery Systems.
Specifications
3Flow restriction limit for Acetaminophen and Ibuprofen
Flow restriction limit for Pseudoephedrine
Flow restriction limit for Dextromethorphan and Diphenhydramine
Related CFR Sections (4)
- 21CFR807.3§ 807.3 Definitions.
(a) Act means the Federal Food, Drug, and Cosmetic Act.Read full regulation →
- 21CFR201.100§ 201.100 Prescription drugs for human use.
A drug subject to the requirements of section 503(b)(1) of the act shall be exempt from section 502(f)(1) if all the following conditions are met:Read full regulation →
- 21CFR314.93§ 314.93 Petition to request a change from a listed drug.
(a) The only changes from a listed drug for which the agency will accept a petition under this section are those changes described in paragraph (b) of this section. Petitions to submit ANDAs for other changes from a listed drug will not be approved.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 →
Enforcement Impact
Deficiencies cited in Warning Letters referencing the same regulations
Recent Cases
- 2025-01-28
Unapproved New Drugs/Misbranded
Mihon Corp. d/b/a VitalityVita and Boulla, LLC
- 2023-12-26
Finished Pharmaceuticals/Unapproved New Drug/Misbranded
East Fork Cultivars
- 2023-03-14
Finished Pharmaceuticals/Unapproved New Drug/Misbranded
ElectRx and Health Solutions, LLC
- 2023-01-17
Finished Pharmaceuticals/Unapproved New Drug/Misbranded
HIS Enterprise Inc dba Adam’s Secret USA, LLC
- 2021-12-21
CGMP/Finished Pharmaceuticals/Unapproved New Drug/Misbranded/Adulterated
Guangdong Kemei Pharmaceutical Technology Co. Ltd.
Related Warning Letters (10)
- 2025-01-28
Unapproved New Drugs/Misbranded
Mihon Corp. d/b/a VitalityVita and Boulla, LLC
- 2023-12-26
Finished Pharmaceuticals/Unapproved New Drug/Misbranded
East Fork Cultivars
- 2023-03-14
Finished Pharmaceuticals/Unapproved New Drug/Misbranded
ElectRx and Health Solutions, LLC
- 2023-01-17
Finished Pharmaceuticals/Unapproved New Drug/Misbranded
HIS Enterprise Inc dba Adam’s Secret USA, LLC
- 2021-12-21
CGMP/Finished Pharmaceuticals/Unapproved New Drug/Misbranded/Adulterated
Guangdong Kemei Pharmaceutical Technology Co. Ltd.
- 2021-10-12
CGMP/Finished Pharmaceuticals/Unapproved New Drug/Misbranded/Adulterated
Notarika, S.A. de C.V.
- 2021-05-11
Finished Pharmaceuticals/Unapproved New Drug/Misbranded/Adulterated
Ismar Soluciones Dinámicas S de RL de CV
- 2021-05-11
Finished Pharmaceuticals/Unapproved New Drug/Misbranded
C&G Laboratorios SA de CV
- 2021-04-13
Finished Pharmaceuticals/Unapproved New Drug/Misbranded/Adulterated
MYM Hidrominerales S.A. de C.V.
- 2021-03-09
Finished Pharmaceuticals/Unapproved New Drug/Misbranded/Adulterated
Plasticos Las Palmas, S.A. de C.V
See Also (8)
- CPG Sec. 460.100 Hospital Pharmacies - Status as Drug Manufacturer (Status: Final)
- CPG Sec 430.100 Unit Dose Labeling for Solid and Liquid Oral Dosage Forms (Status: Final)
- Labeling for Biosimilar Products Guidance for Industry (Status: Final)
- Biosimilars and Interchangeable Biosimilars: Licensure for Fewer Than All Conditions of Use for Which the Reference Product Has Been Licensed Guidance for Industry: Draft Guidance for Industry (Status: Draft)
- Labeling for Biosimilar and Interchangeable Biosimilar Products (Status: Draft)
- Content and Format of Composition Statement and Corresponding Statement of Ingredients in Labeling in NDAs and ANDAs (Status: Draft)
- Communications From Firms to Health Care Providers Regarding Scientific Information on Unapproved Uses of Approved/Cleared Medical Products: Questions and Answers (Status: Final)
- Considerations for Waiver Requests for pH Adjusters in Generic Drug Products Intended for Parenteral, Ophthalmic, or Otic Use: Guidance for Industry (Status: Final)