Description
This guidance represents the Food and Drug Administration's (FDA's) current thinking on this topic. It does not create or confer any rights for or on any person and does not operate to bind FDA or the public. You can use an alternative approach if the approach satisfies the requirements of the applicable statutes and regulations.
Key Topics
Terms and concepts identified from this document
Scope & Applicability
Product Classes
3Products containing dietary ingredients intended to supplement the diet; The final product category for which the NDI is intended.
Specific type of dietary supplement subject to the rule
Specific type of dietary supplement subject to the rule
Stakeholders
10Target audience for the compliance guide
individual responsible for evaluating potential risks
may participate in material review by providing analysis
Facility supplying raw materials or ingredients; Facility providing raw materials to a manufacturer
Personnel assigned to ensure compliance by individuals with the requirements of part 121
Personnel responsible for review, approval, or rejection requirements; Responsible for reviewing and approving calibrations, controls, and documentation.; Individuals responsible for approving or rejecting processes and materials; responsible for material review and disposition decisions; Responsible for approving repackaging or relabeling; Quality control personnel conduct a material review and make a disposition decision.
Contract acceptor for transportation of APIs
Entity responsible for submitting NDINs
Entity required to comply with cigarette warning requirements
Licensed individual who orders the use of the prescription device
Regulatory Context
Document Types
6ensure that the dietary supplement is packaged and labeled as specified in the master manufacturing record; Required documentation for manufacturing operations; Required documentation under Subpart H; Document specifying how the dietary supplement is to be packaged and labeled.; Specifies how dietary supplements are packaged and labeled; deviations from this record trigger material review; written record required for each unique formulation and batch size; Requirements for packaging and labels m
Records in electronic form created or maintained under Agency regulations
A qualified person review all product complaints.
Requesting sesame be regulated similarly to major food allergens
Records documenting the manufacturing of a batch
Document indicating analytical results of testing; record relied on to control L. monocytogenes in ingredients; document provided for a food prior to or upon receipt of the food; COA documentation
Attributes
3Metric used to define a small business
Determines holding period for reserve samples; Keep written records for one year past the shelf life date.
Property of a device that may be changed via established protocols
Technical Details
Substances
4Vitamins, minerals, herbs used in dietary supplements
specific regulatory requirements apply
common component that may contribute to total bioburden
Material incorporated into dietary supplements
Testing Methods
6A scientific method that is accurate, precise, and specific for its intended purpose.; required for each established specification to determine if it is met
Recommended for performing tests or examinations
Method for identifying finished batches for representative sampling
used to demonstrate relevance of previous toxicity testing
One of the methods used to determine whether specifications are met.
Subpart J – Production and Process Control: Requirements for Laboratory Operations
Processes
10interim final rule setting forth a procedure for requesting an exemption from a requirement for the manufacturer to conduct at least one appropriate test to verify identity; Verification of the identity of each dietary ingredient
Measure taken to destroy undesirable microorganisms
Required direction for water, bottles, and nipples
Cleaning and sanitizing procedures for food processing environments; General sanitation program and monitoring recommendations; Sanitation procedures to minimize Listeria contamination; Routine cleaning and sanitizing schedules
processes including sampling plans and testing methods
Storage or identification of an ACTP in a physically separate area to prevent improper release.
Evaluation by quality control personnel before disposition; evaluation of components or products that fail specifications; Conduct a material review and make a disposition decision for returned products.
End-user sterilization validation
Corrective measure when agricultural water does not meet numerical criteria
Required for critical equipment to maintain quality
Clinical Concepts
1Adverse events resulting in death, hospitalization, or significant disability.
Identified Hazards
Hazards
3Risk associated with tattoo inks that can lead to infection.; Risk associated with insanitary conditions in tattoo ink preparation
Microorganisms or particulate matter that could adversely affect the device.
Potential for contamination of covered produce; Known or reasonably foreseeable hazards in water
Standards & References
External Standards
3United States Pharmacopeia standards for compendial drug substances; confirming conformance to the application-approved specification and USP
Use of a method published by an authoritative source such as AOAC International
recommended for use in performing tests and examinations
Specifications
10Specifications to identify dietary ingredients, other ingredients, and contaminants
Failure of the product to meet product specifications
expected yield at each point of the manufacturing process
limits that must be met for finished batches
Specification for components
Component and product specification
Concentration of the active pharmaceutical ingredient
Drug product purity should be carefully evaluated early in product development.
Final product release criteria
Documentation for meeting specifications for identity, purity, strength, and composition
Related CFR Sections (20)
- 21CFR111.560§ 111.560 What requirements apply to the review and investigation of a product complaint?
(a) A qualified person must:Read full regulation →
- 21CFR111.510§ 111.510 What requirements apply when a returned dietary supplement is received?
You must identify and quarantine returned dietary supplements until quality control personnel conduct a material review and make a disposition decision.Read full regulation →
- 21CFR111.470§ 111.470 What requirements apply to distributing dietary supplements?
You must distribute dietary supplements under conditions that will protect the dietary supplements against contamination and deterioration.Read full regulation →
- 21CFR111.465§ 111.465 What requirements apply to holding reserve samples of dietary supplements?
(a) You must hold reserve samples of dietary supplements in a manner that protects against contamination and deterioration. This includes:Read full regulation →
- 21CFR111.83§ 111.83 What are the requirements for reserve samples?
(a) You must collect and hold reserve samples of each lot of packaged and labeled dietary supplements that you distribute.Read full regulation →
- 21CFR111.460§ 111.460 What requirements apply to holding in-process material?
(a) You must identify and hold in-process material under conditions that protect against mixup, contamination, and deterioration.Read full regulation →
- 21CFR111.455§ 111.455 What requirements apply to holding components, dietary supplements, packaging, and labels?
(a) You must hold components and dietary supplements under appropriate conditions of temperature, humidity, and light so that the identity, purity, strength, and composition of the components and dietary supplements are not affected.Read full regulation →
- 21CFR111.420§ 111.420 What requirements apply to repackaging and relabeling?
(a) You may repackage or relabel dietary supplements only after quality control personnel have approved such repackaging or relabeling.Read full regulation →
- 21CFR111.415§ 111.415 What requirements apply to filling, assembling, packaging, labeling, and related operations?
You must fill, assemble, package, label, and perform other related operations in a way that ensures the quality of the dietary supplement and that the dietary supplement is packaged and labeled as specified in the master manufacturing record. You must do this using any effective means, including theRead full regulation →
- 21CFR111.410§ 111.410 What requirements apply to packaging and labels?
(a) You must take necessary actions to determine whether packaging for dietary supplements meets specifications so that the condition of the packaging will ensure the quality of your dietary supplements;Read full regulation →
- 21CFR111.370§ 111.370 What requirements apply to rejected dietary supplements?
You must clearly identify, hold, and control under a quarantine system for appropriate disposition any dietary supplement that is rejected and unsuitable for use in manufacturing, packaging, or labeling operations.Read full regulation →
- 21CFR111.365§ 111.365 What precautions must you take to prevent contamination?
You must take all the necessary precautions during the manufacture of a dietary supplement to prevent contamination of components or dietary supplements. These precautions include:Read full regulation →
- 21CFR111.360§ 111.360 What are the requirements for sanitation?
You must conduct all manufacturing operations in accordance with adequate sanitation principles.Read full regulation →
- 21CFR111.355§ 111.355 What are the design requirements for manufacturing operations?
You must design or select manufacturing processes to ensure that product specifications are consistently met.Read full regulation →
- 21CFR111.320§ 111.320 What requirements apply to laboratory methods for testing and examination?
(a) You must verify that the laboratory examination and testing methodologies are appropriate for their intended use.Read full regulation →
- 21CFR111.310§ 111.310 What are the requirements for the laboratory facilities that you use?
You must use adequate laboratory facilities to perform whatever testing and examinations are necessary to determine whether:Read full regulation →
- 21CFR111.255§ 111.255 What is the requirement to establish a batch production record?
(a) You must prepare a batch production record every time you manufacture a batch of a dietary supplement;Read full regulation →
- 21CFR111.205§ 111.205 What is the requirement to establish a master manufacturing record?
(a) You must prepare and follow a written master manufacturing record for each unique formulation of dietary supplement that you manufacture, and for each batch size, to ensure uniformity in the finished batch from batch to batch.Read full regulation →
- 21CFR111.170§ 111.170 What requirements apply to rejected components, packaging, and labels, and to rejected products that are received for packaging or labeling as a dietary supplement?
You must clearly identify, hold, and control under a quarantine system for appropriate disposition any component, packaging, and label, and any product that you receive for packaging or labeling as a dietary supplement (and for distribution rather than for return to the supplier), that is rejected aRead full regulation →
- 21CFR111.165§ 111.165 What requirements apply to a product received for packaging or labeling as a dietary supplement (and for distribution rather than for return to the supplier)?
(a) You must visually examine each immediate container or grouping of immediate containers in a shipment of product that you receive for packaging or labeling as a dietary supplement (and for distribution rather than for return to the supplier) for appropriate content label, container damage, or broRead full regulation →
Enforcement Impact
Deficiencies cited in Warning Letters referencing the same regulations
Recent Cases
- 2025-12-16
Seafood HACCP/CGMP for Foods/Adulterated/Insanitary Conditions
Harbor Marine Product Inc.
- 2025-09-30
CGMP/Dietary Supplement/Adulterated/Misbranded
Valentine Enterprises, Inc.
- 2025-09-30
CGMP/Dietary Supplement/Adulterated/Misbranded
Time Challenger Labs International, Inc.
- 2025-09-30
CGMP/Dietary Supplement/Adulterated/Misbranded
Vidaslim Co.
- 2025-09-30
CGMP/Food/Prepared, Packed or Held Under Insanitary Conditions/Adulterated
Hans Bakery Inc. d/b/a Andersen’s Bakery
Related Warning Letters (10)
- 2025-12-16
Seafood HACCP/CGMP for Foods/Adulterated/Insanitary Conditions
Harbor Marine Product Inc.
- 2025-09-30
CGMP/Dietary Supplement/Adulterated/Misbranded
Valentine Enterprises, Inc.
- 2025-09-30
CGMP/Dietary Supplement/Adulterated/Misbranded
Time Challenger Labs International, Inc.
- 2025-09-30
CGMP/Dietary Supplement/Adulterated/Misbranded
Vidaslim Co.
- 2025-09-30
CGMP/Food/Prepared, Packed or Held Under Insanitary Conditions/Adulterated
Hans Bakery Inc. d/b/a Andersen’s Bakery
- 2025-09-16
Unapproved New Drugs/Misbranded
Mericon Industries, Inc.
- 2025-08-19
Seafood HACCP/CGMP for Foods/Adulterated
Chaohu Daxin Foodstuffs Co., Ltd.
- 2025-06-24
Seafood HACCP/CGMP for Foods/Adulterated/Insanitary Conditions
Yongdae Hwangtae Union Corp Daeryung
- 2025-06-24
CGMP/Dietary Supplement/Adulterated/Misbranded
M.O.M. Enterprises, LLC
- 2025-06-03
Unapproved New Drugs/Misbranded
Mother Earth Minerals, Inc.
See Also (8)
- Guidance for Industry: Foreign Supplier Verification Programs for Importers of Food for Humans and Animals (Status: Final)
- Temporary Policy Regarding Preventive Controls and FSVP Food Supplier Verification Onsite Audit Requirements Due to COVID-19: Guidance for Industry (Status: Final)
- Draft Guidance for Industry: Considerations for Determining Whether a Measure Provides the Same Level of Public Health Protection as the Corresponding Requirement in 21 CFR part 112 or the Preventive Controls Requirements in part 117 or 507 (Status: Draft)
- Small Entity Compliance Guide: Foreign Supplier Verification Programs for Importers of Food for Humans and Animals (Status: Final)
- Small Entity Compliance Guide: What You Need to Know About Current Good Manufacturing Practice, Hazard Analysis, and Risk-Based Preventive Controls for Human Food (Status: Final)
- Small Entity Compliance Guide on Structure/Function Claims (Status: Final)
- COVID-19: Developing Drugs and Biological Products for Treatment or Prevention: Guidance for Industry (Status: Final)
- Chapter 1 - General (Status: Final)