Understanding Labeling Definitions in the United States: Navigating FDC Act, QSR, and QMSR Requirements

When considering global expansion of medical devices, the U.S. market occupies a critically important position. However, entering the U.S. market requires meeting strict regulatory requirements from the U.S. Food and Drug Administration (FDA). The requirements for medical device labeling play an especially critical role in ensuring product safety and effectiveness. This article explains the definitions and requirements for labeling under the U.S. Federal Food, Drug, and Cosmetic Act (FDC Act), the Quality System Regulation (QSR), and the Quality Management System Regulation (QMSR), which takes effect on February 2, 2026.

Definition of Labeling in the FDC Act and Exceptions

The U.S. Federal Food, Drug, and Cosmetic Act (FDC Act) provides clear definitions regarding labeling. Specifically, Section 201(m) of the FDC Act defines labeling as:

All labels and other written, printed, or graphic matter (1) upon any article or any of its containers or wrappers, or (2) accompanying such article.

Meanwhile, Section 201(k) defines a label as:

A display of written, printed, or graphic matter upon the immediate container of any article.

In other words, the FDC Act can be organized as follows:

Label: Device nameplate (including UDI), and materials affixed to or imprinted on primary packaging and secondary packaging (boxes)

Labeling: All printed materials that come to the attention of users and patients (including instructions for use, package inserts, catalogs, promotional materials, and website content)

As is clear from these definitions, the concept of labeling is broader than that of label alone, encompassing all documents and display materials related to the product. Through this expansive definition, the FDA intends to ensure that important information regarding product safety and effectiveness is reliably communicated through labeling.

Exceptions to Labeling

While the definition of labeling is broad, not all documents are considered labeling. A representative exception is shipping documents (such as bills of lading). These documents are generally not considered labeling for the following reasons:

1. Shipping documents are typically commercial documents used for managing product transportation and are not ultimately viewed by users or patients
2. They are documents used purely for logistics purposes and do not contain information about product usage, performance, or indications for use
3. They do not meet the requirement of “accompanying” the product; they are used only during transportation and are not provided to end users as part of the product

However, it is important to note that if shipping documents contain information about product safety or use and are provided to end users, they may exceptionally be considered labeling.

Similarly, other documents used purely for commercial purposes (e.g., purchase orders, invoices) are generally not considered labeling, provided they do not contain information about product usage or performance. Here too, if these documents contain information about product usage, indications for use, or performance, the FDA may interpret them as labeling.

Thus, while the definition of labeling is comprehensive, it should be understood that its interpretation and application are determined based on the relationship between the product and the documents and their content.

Common Problems in Labeling Management and Responses

A problem that frequently arises in practical labeling management of medical devices is the creation and distribution of unofficial documents. For example, there are cases where sales departments independently create and distribute simplified manuals because the instructions for use are thick and difficult to read. Such actions constitute serious quality control problems and are not acceptable. The reasons are as follows:

Regulatory Issues: Simplified manuals also constitute “labeling” under the FDC Act and QSR/QMSR regulatory requirements. Distribution of documents that have not gone through formal approval processes is highly likely to constitute regulatory violations.

Lack of Design Control Process: Labeling is part of design output and is required to undergo rigorous processes such as design review, verification, and validation. Documents created independently have not undergone these processes.

Risk Management Issues: Unofficial documents carry the risk of containing incorrect or incomplete information, which can directly affect the safety of patients and users.

Lack of Consistency: Discrepancies in information may arise between official instructions for use and unofficial simplified manuals, which can lead to user confusion.

To prevent such problems, the following countermeasures are important:

1. Provide education to all departments (especially sales and marketing) about the definition of labeling and its regulatory importance
2. Clarify document creation processes and establish procedures to ensure all product-related documents undergo appropriate approval processes
3. Improve the usability of instructions for use themselves to address the need for creating simplified manuals
4. Build systems that enable easy searching and reference of necessary information within official instructions for use using digital tools

In transitioning to the QMSR, it is important to focus on these unofficial document issues and strengthen labeling management systems.

Design Control of Labels and Labeling

In the QSR (Quality System Regulation), labels and labeling are clearly positioned as outputs from design. This means they are treated as important elements for ensuring the quality and safety of medical devices, not merely as means of communicating product information.

Specifically, the following requirements apply:

Positioning as Design Output: Labels and labeling are treated as outputs of the design development process and require strict management similar to other design elements.

Inclusion in DHF: Records related to the design of labels and labeling must be included in the Design History File (DHF). This includes the change history and rationale from initial design drafts to final versions.

Mandatory Design Review: Labels and labeling must undergo formal design review processes similar to other design elements. This ensures appropriateness, accuracy, and completeness.

Verification and Validation: Verification and validation are required to determine whether the content of labels and labeling achieves the intended purpose and whether users can understand them appropriately.

Even after transitioning to the QMSR, these basic requirements will be maintained. In ISO 13485:2016, the term “design development file” is used and treated as equivalent to the QSR’s “DHF.” What is important is that under the QMSR, labels and labeling continue to be treated as an integral part of the design control process.

Medical device manufacturers are required to plan the development of labels and labeling from the early stages of product development and proceed under appropriate design control. This ensures that final labels and labeling meet regulatory requirements and effectively communicate accurate information to users.

Digital Content and Labeling

Based on the broad definition of labeling in the FDC Act, it is important to note that digital content is also subject to regulation. In particular, product information on medical device manufacturers’ websites may be interpreted by the FDA as “labeling.”

The FDA regularly monitors medical device companies’ websites and may issue Warning Letters when it discovers content that violates regulatory requirements. The following types of content are primarily subject to such monitoring:

• Recommendations for unapproved off-label uses
• Recommendations for unapproved or unintended uses
• Minimizing risks and exaggerating effects
• Misleading comparative advertising
• Claims of efficacy with insufficient evidence

Medical device manufacturers need to properly manage digital content as “labeling.” In practice, it is important to include website information within the scope of the quality management system and ensure it undergoes appropriate review and approval processes. When responding to the QMSR, it is recommended to build a comprehensive labeling management system that includes digital content management.

Comparison of Labeling Definitions in ISO 13485 and FDC Act

In ISO 13485:2016, “labelling” is defined as written, printed, or graphic matter placed on the product itself, container, or packaging to convey product identification, technical information, and safety information. It should be noted that this definition references terminology defined in ISO 9000:2015.

On the other hand, when compared with the “labeling” definition in the FDC Act mentioned earlier, the following key differences exist:

1. Scope Breadth

FDC Act Labeling is very broad and includes all documents “accompanying” the product. This can include instructions for use, package inserts, pamphlets, websites, and promotional materials.

ISO 13485 Labelling focuses primarily on identification and information directly placed on the product itself, its container, or packaging, representing a more limited definition.

2. Spelling Differences

• FDC Act uses “labeling” (U.S. spelling)
• ISO 13485 uses “labelling” (UK spelling)

This difference is not merely about spelling but becomes an important distinction in legal documents.

3. Legal Positioning

• The labeling definition in the FDC Act has legal binding force and forms the basis for regulation
• The labelling definition in ISO 13485 has a stronger guidance character and is based on international consensus

In the QMSR, while ISO 13485:2016 is incorporated by reference, it is clearly stated that the FDC Act definition of “labeling” takes precedence. This is characteristic in that it maintains legal consistency while achieving harmonization with ISO 13485.

Labeling Requirements in QSR

The current Quality System Regulation (21 CFR Part 820) clearly stipulates requirements for labeling. While the QSR targets quality control of the entire medical device manufacturing process, labeling occupies an important position within it. The main requirements for labeling in the QSR are as follows:

• Labeling must be an output from design and must be saved in the DHF (Design History File) after undergoing design review
• Detailed procedures must be documented and implemented to ensure the integrity of labels and packaging
• Procedures must be established regarding inspection, storage, and handling activities related to labeling

It is particularly noteworthy that the QSR requires strict control of labeling and packaging. This is because product mix-ups and labeling errors can lead to serious product recalls and safety issues.

Differences in Labeling Inspection Requirements

In ISO 13485:2016, Clause 7.5.1(e) states that “defined work for labeling and packaging shall be carried out,” but the FDA judged this requirement alone to be insufficient. Specifically, the FDA considers that requirements for labeling inspection are not sufficiently described, which is also mentioned in the QMSR preamble.

The FDA particularly positions the management of labeling and packaging as an important element directly related to product identification and safety, and, based on the understanding that incorrect labeling and packaging are the cause of many medical device recalls, has shown a policy of maintaining more detailed and strict requirements.

Against this background, the QMSR establishes additional labeling inspection requirements in addition to Clause 7.5.1. This is a point that medical device manufacturers should pay particular attention to as a U.S. market-specific requirement.

Changes to Labeling Requirements in QMSR

On February 2, 2024, the FDA published the final rule for the Quality Management System Regulation (QMSR). The QMSR incorporates by reference ISO 13485:2016, the international standard for medical device quality management systems established by the International Organization for Standardization (ISO). This regulation is scheduled to take effect on February 2, 2026, and until then, manufacturers must continue to comply with the current QSR.

Labeling requirements in the QMSR are basically based on ISO 13485:2016 requirements, but the FDA judged that ISO 13485 does not adequately address labeling inspection aspects and has retained some provisions from the current QSR. Specifically, the following points are noteworthy:

• QMSR Section 820.45 continues to require “procedures that provide a detailed description to ensure the integrity, inspection, storage, and operations of labeling and packaging activities”
• While ISO 13485:2016 Clause 7.5.1(e) states “defined work for labeling and packaging shall be carried out,” the FDA judges this alone to be insufficient
• Even after the QMSR takes effect, specific requirements for medical device labeling stipulated in 21 CFR Part 801 (Labeling) continue to apply

Thus, with the transition to the QMSR, labeling requirements are organized in a form conforming to ISO 13485:2016, but important FDA-specific elements are maintained.

Changes to Record Management in QMSR and Impact on Labeling

Changes are also seen in terminology related to record types in the QMSR. Terms used in the current QSR such as “Design History File (DHF),” “Device Master Record (DMR),” and “Device History Record (DHR)” will no longer be used in the QMSR. However, the elements included in these records continue to be required in a form encompassed by concepts such as the “Medical Device File (MDF)” in ISO 13485:2016.

Records related to labeling will also be affected by this change, but basic requirements for record retention are maintained. Labeling continues to be positioned as output from design and needs to be properly documented and managed.

Global Harmonization and Future of Labeling Requirements

The introduction of the QMSR is part of an effort to harmonize FDA regulatory requirements with global standards. ISO 13485:2016 is already harmonized under the European Union Medical Device Regulation (EU MDR), and with the introduction of the QMSR, medical device manufacturers are expected to be able to reduce duplicate work for responding to multiple regulatory frameworks.

Regarding labeling, while there are differences in specific content required by region, international harmonization is progressing with respect to basic management approaches. However, it should be noted that the FDA maintains its own strict requirements specifically for labeling and packaging management. This is against the background that labeling and packaging deficiencies are a major cause of medical device recalls in the United States.

Practical Response Measures

For medical device manufacturers, the following points are important as practical response measures in preparation for the transition to the QMSR:

1. Compare current labeling management procedures with ISO 13485:2016 requirements and perform gap analysis
2. Confirm additional procedures for labeling and packaging required by QMSR Section 820.45 and update procedures as necessary
3. Review labeling record retention methods and adjust to conform to QMSR requirements
4. Verify labeling design and review processes and evaluate whether they are appropriately implemented, including from a risk management perspective
5. Based on the broad labeling definition in the FDC Act, build a system to properly manage all product-related documents and information (instructions for use, package inserts, promotional materials, website content, etc.)
6. Pay particular attention to the point that “advertising” and “promotional materials” may be considered labeling in the U.S. market and become subject to regulation, and include these materials within the scope of the quality management system

By proceeding with these responses in a planned manner, smooth transition to the QMSR enforcement on February 2, 2026, becomes possible. It should be noted that responding to the QMSR requires substantive responses based on a thorough understanding of the differences in labeling definitions, not merely formal document changes.

Spelling Differences and Legal Impact

It is important to note that there are also spelling differences in labeling between ISO 13485 and the FDC Act. While ISO 13485 uses the UK spelling “labelling,” the FDC Act uses the U.S. spelling “labeling.” While this may appear to be merely a notation difference, it becomes an important distinction in legal documents.

The preamble to the final QMSR rule also mentions this difference, clarifying that the FDC Act spelling and definition take precedence. When developing internal documents and procedures, medical device manufacturers should use the FDA-compliant “labeling” spelling in documents intended for the U.S. market.

Comparison Table: Key Differences in Labeling Definitions

Aspect	FDC Act (U.S.)	ISO 13485:2016 (International)
Definition Scope	Very broad – includes all materials “upon” or “accompanying” the product (instructions, inserts, promotional materials, websites)	More limited – focuses on written/printed matter on the product, container, or packaging itself
Spelling	“Labeling” (U.S. spelling)	“Labelling” (UK spelling)
Legal Status	Legally binding under federal law; forms basis for enforcement	International standard; consensus-based guidance
Website Content	Can be considered labeling if product-related	Generally not explicitly addressed
Promotional Materials	Can be considered labeling	Generally not explicitly addressed
Primary Focus	Information communication and regulatory compliance	Product identification and technical information
QMSR Application	FDC Act definition takes precedence	Referenced but supplemented by FDC Act requirements

Conclusion

The definitions and requirements for labeling in the U.S. FDC Act, QSR, and QMSR are extremely important for ensuring the safety and effectiveness of medical devices. With the transition from QSR to QMSR, the basic framework is organized in a form conforming to ISO 13485:2016, but the FDA maintains its own strict requirements for labeling and packaging.

As a particularly noteworthy point, there are significant differences in scope and legal positioning between the labeling definition in the FDC Act and the labelling definition in ISO 13485. While the FDC Act broadly captures labeling to include all documents and information accompanying the product, ISO 13485 defines it more restrictively. Understanding this difference is extremely important for appropriate response to the QMSR.

By thoroughly understanding these changes and definitional differences and implementing appropriate countermeasures, medical device manufacturers can ensure compliance with regulatory requirements while promoting international expansion more efficiently. While the preparation period until the QMSR takes effect on February 2, 2026 remains, it is advisable to start reviewing labeling management procedures and records at an early stage.

While appropriately responding to FDA regulatory changes is not easy, by understanding the flow of global regulatory harmonization and addressing it in a planned manner, it becomes possible to build a more efficient and effective quality management system.