Labeling provides critical details about an IVD, including its intended use, limitations, and performance characteristics. Proper labeling is necessary to ensure safe and effective usage. The labeling must be truthful, non-misleading, and must accompany the IVD during clinical use to prevent misbranding.
21 CFR Part 809.10, part of the FDA’s Medical Device Labeling requirements, mandates calibration details and performance characteristics for IVDs. These details, along with the Unique Device Identifier (UDI) system, enhance patient safety and prevent counterfeiting. Each IVD must have a UDI label and be registered in the FDA’s Global Unique Device Identification Database (GUDID) for tracking purposes.
Special considerations apply to Clinical Laboratory Improvement Amendments (CLIA) waiver devices, Point-of-Care (POC) testing devices, and home-use IVDs. CLIA-waived devices must be labeled as user-friendly with a low likelihood of inaccurate results, while POC testing devices require clear, easy-to-follow instructions and safety precautions for lay users.
Additionally, the FDA allows electronic labelling for certain IVDs, provided that users can easily access the required information.
General Labeling Requirements for IVDs: labeling of IVD is crucial for proper identification, usage, and compliance with 16 CFR Part 1500. Labels must include proprietary names, intended use, reactive ingredients declaration, warnings, storage instructions, lot or control number for traceability, and manufacturer, packer, or distributor information. Multiple-unit products must be traceable at the individual unit level for uniform identification. Sterilization information in IVD (In Vitro Diagnostic) label is mandatory for FDA 510k submission.
Immediate Container Labeling its name, warnings, manufacturer details, and traceable lot number. If space allows additional information like intended use, active ingredient concentration, and storage instructions should be included, otherwise, it should appear on the outer label.
Labeling Requirements for Reagents, Instruments vary based on the type of IVD product:
- Reagents: Labels must declare the common name, active ingredient quantity or concentration, biological material source and activity, storage instructions, reconstitution or mixing directions, purity verification methods, and stability indicators.
- Instruments: Labels must outline the function, installation requirements, principles of operation, performance specifications, calibration methods, operating instructions, hazards, and maintenance information.
- Labeling Requirements for IVD Systems: An IVD system consists of multiple components (e.g., instruments, reagents, and software). Labeling should include System Overview, Intended Use, Performance Characteristics, Operating Instructions, Warnings and Limitations.
Difference in requirements for reagents and instruments
Labeling for General-Purpose and Analytical Reagents
General-purpose laboratory reagents and equipment (e.g., hydrochloric acid, pipettes, beakers) require basic labelling requirements such as product identification, purity and quality statement, storage conditions, manufacturer details, and warning statements including “For Laboratory Use“ for non-IVD reagents.
Analyte Specific Reagents (ASRs), such as monoclonal antibodies and nucleic acid probes, include product identification, composition details, biological source, activity level, measurement units, warnings, storage conditions, purity information, and regulatory statements for Class I ASRs, such as “ASR: Analytical and Performance Characteristics are Not Established.”
Specimen Collection, Preparation, and Analysis: Labeling must provide detailed instructions for specimen collection, including special precautions, necessary additives, potential interfering substances, and storage/handling guidelines. Additionally, a step-by-step procedure for processing specimens should be included, covering required materials, reagent quantities, calibration range, and quality control measures. The labeling must also specify how to calculate results, describe expected values, highlight limitations of the procedure, and provide a bibliography and manufacturer details.
Home-Use IVD Labeling: FDA mandates clear, concise labeling for home-use IVDs, including the intended use, contraindications, and a summary of the test’s benefits and limitations. Package inserts should include a list of potential interferences, step-by-step test procedures, images, troubleshooting guidance, and a toll-free number for inquiries.
Labeling Exemptions Certain IVD products may be exempt from full labeling requirements like Laboratory research phase products must be labeled “For Research Use Only,” pre-commercial investigational products must be labeled “For Investigational Use Only,” general-purpose reagents and equipment do not require detailed instructions, and analyte-specific reagents (ASRs) must include product identification, composition details, biological source, activity level, purity, warnings, storage conditions, and regulatory statements.
Submission of Labeling at the Time of Device Listing
The FDA intends to request labeling submission at the time of device listing for specific categories of LDTs(Laboratory developed test). These include LDTs that were first marketed before May 6, 2024, provided they have not been modified beyond the scope described in the preamble to the LDT Final Rule. Additionally, LDTs addressing unmet needs within an integrated healthcare system and those approved by the New York State Clinical Laboratory Evaluation Program (NYS CLEP) will also be subject to this requirement.
Use of Symbols in IVD Labelling
The FDA permits standardized symbols for professional-use IVDs to enhance efficiency and clarity, provided they align with ISO 15223 and EN 980 for international standardization. Manufacturers must include a symbols glossary in the labelling package, as failure to meet FDA criteria may result in the device being misbranded under Section 502(c) of the Act. Symbols can indicate IVD use, handling/storage instructions, expiration dates, manufacturer details, and safety warnings, but they are not allowed for OTC or home-use devices. FDA-cleared 510(k) and PMA devices can adopt symbols without new submissions, unless the change impacts safety or effectiveness, and any adverse events from misinterpretation must be reported under 21 CFR Part 803.
Conclusion
FDA labelling requirements for IVD devices are designed to ensure accuracy, safety, and regulatory compliance. Proper labelling minimizes errors and enhances patient safety by providing clear instructions, performance data, and risk warnings. Whether for immediate containers, reagents, systems, or instruments, compliance with 21 CFR 809.10 is essential for manufacturers to secure FDA approval and market their products successfully. Adhering to these guidelines ensures that healthcare professionals and laboratories can effectively use IVD devices, improving diagnostic accuracy and patient outcomes.
Author:
Ms Suman Mishra (M. Pharm)
Regulatory Consultant, FDA Compliance | Medical Device
I3CGlobal