Chapter 10: Labeling - Comprehensive Notes

Introduction

  • The global medical device industry is experiencing a steep increase in annual sales, projected to reach approximately 800800 billion USD by 2030, with an annual increase of over 5%.
  • Regulations governing market access for medical devices are undergoing accelerated and significant changes.
  • Increased scrutiny of medical devices is expected due to these trends.
  • Accurate and compliant labeling is crucial for demonstrating compliance with regulatory standards, ensuring market access, and enabling safe and effective use of medical devices.
  • Device traceability is achieved with Unique Device Identifier (UDI) application.

Definition of Label

  • According to ISO 13485, a label includes any information related to:
    • Identification
    • Technical description
    • Intended purpose
    • Proper use of the device
  • This information can be provided in various formats:
    • Directly on the device and its user interface
    • Device packaging
    • User manuals
    • Patient materials
    • Video recordings
    • Point-of-sale displays
  • The primary purpose of labeling is to ensure user safety, with secondary purposes including traceability and brand protection.

Importance of Compliant Labeling

  • Medical device labeling is extensively analyzed during product authorization applications.
  • Non-compliant labeling can result in:
    • Delays in market entry
    • Application denials
    • Risk of improper device use
    • Product recalls
    • Export bans
    • Financial penalties
    • Damage to reputation
  • Mislabeling is a leading cause of medical device recalls, according to MedTech Dive.
  • This chapter provides a summary of medical device labeling regulations, their application with standards and guidances, and upcoming or proposed changes, focusing on:
    • North America (United States, Canada, and Puerto Rico)
    • Europe (European Union, Non-European Union countries, United Kingdom, Wales)
    • Asia (China, Japan, India, South Korea)
    • Latin America (Mexico, Brazil, and Colombia)
    • Oceania (Australia and New Zealand)
  • The chapter also considers software as a medical device (SaMD), with further details in Chapter 37.

North America

United States

  • In the US, device classification impacts labeling requirements, particularly regarding claims.
  • All medical devices must comply with regulations in Table 10-1:
    • 21 CFR Part 801: Labeling
    • 21 CFR Part 820: Quality System Regulation
    • 21 CFR Part 830: Unique Device Identification
  • Devices regulated by specific regulatory panels must comply with regulations in Table 10-2:
    • 21 CFR Part 809: In Vitro Diagnostic Products for Human Use
    • 21 CFR Part 862: Clinical Chemistry and Clinical Toxicology Devices
    • 21 CFR Part 864: Hematology and Pathology Devices
    • 21 CFR Part 866: Immunology and Microbiology Devices
    • 21 CFR Part 868: Anesthesiology Devices
    • 21 CFR Part 870: Cardiovascular Devices
    • 21 CFR Part 872: Dental Devices
    • 21 CFR Part 874: Ear, Nose, and Throat Devices
    • 21 CFR Part 876: Gastroenterology-Urology Devices
    • 21 CFR Part 878: General and Plastic Surgery Devices
    • 21 CFR Part 880: General Hospital and Personal Use Devices
    • 21 CFR Part 882: Neurological Devices
    • 21 CFR Part 884: Obstetrical and Gynecological Devices
    • 21 CFR Part 886: Ophthalmic Devices
    • 21 CFR Part 888: Orthopedic Devices
    • 21 CFR Part 890: Physical Medicine Devices
    • 21 CFR Part 892: Radiology Devices
    • 21 CFR Part 1010: Performance Standards for Electronic Products: General
  • The FDA allows manufacturers to declare conformity to recognized consensus standards.
  • Commonly accepted consensus standards for medical devices (Table 10-3):
    • ISO 13485:2016: Medical Devices - Quality Management Systems - Requirements for regulatory purposes
    • ISO 20417:2021: Medical Devices - Information to be supplied by the manufacturer
    • ISO 15223-1:2021: Medical devices - Symbols to be used with information to be supplied by the manufacturer - Part 1: General requirements
  • ISO 15223 may be used to present labeling elements through internationally recognized symbols.
  • Further standards may be applied where relevant (Table 10-4):
    • ANSI AAMI C186:2017: Cochlear implant systems: Requirements for safety, functional verification, labeling and reliability reporting
    • ANSI AAMI ST67:2019: Sterilization of health care products - Requirements and guidance for selecting a sterility assurance level (SAL) for products labeled "sterile"
    • ANSI IES RP-27.3-17: Recommended Practice for Photobiological Safety for Lamps - Risk Group Classification and Labeling
    • ASTM F2943-14 (Reapproved 2019): Standard Guide for Presentation of End User Labeling Information for Orthopedic Implants Used in Joint Arthroplasty
    • CLSI AUTO12-A: Specimen Labels: Content and Location, Fonts, and Label Orientation; Approved Standard
    • ISO 71776:1996-15: Wheelchairs - Part 15: Requirements for information disclosure, documentation and labeling
    • ISO 18369-1:2017: Ophthalmic optics - Contact lenses - Part 1: Vocabulary, classification system and recommendations for labelling specifications
    • ISO 27185:2012: Cardiac rhythm management devices - Symbols to be used with cardiac rhythm management device labels, and information to be supplied - General requirements
    • RESNA ANSI WC-1:2019 American National Standard for Wheelchairs - Volume 1: Requirements and Test Methods for Wheelchairs (including Scooters) Section 15: Requirements for Information Disclosure, Documentation and Labeling
  • All device labeling must be in English, as per 21 CFR, except when distributed solely in US territories like Puerto Rico, where Spanish is predominant.
  • For investigational devices in clinical studies, manufacturers can follow the labeling requirements in 21 CFR Part 812 - Investigational Device Exemptions, allowing deviation from 21 CFR Part 801 and 21 CFR Part 830.
  • IVDs may comply with 21 CFR Part 809 instead of 21 CFR Part 801.
  • Manufacturers claiming compliance with 21 CFR Part 820 must validate that the device meets its intended use and user needs through design validation.

Canada

  • Medical device and IVD labeling is regulated by the Canadian Medical Devices Regulations (MDR), SOR/98-282, and the Food and Drugs Act (F&DA), R.S.C. F-27.
  • Specific labeling elements based on device classification are found in both regulations.
  • MDR Sections 21-23 cover required labeling elements.
  • F&DA Sections 3, 20, and 21 outline required labeling elements.
  • As of January 2019, manufacturers must demonstrate compliance with the Medical Device Single Audit Program (MDSAP).
  • MDSAP and ISO 13485 share overlapping requirements for device labeling, ensuring labels remain intact and legible throughout the device lifecycle.
  • Section 21 of the MDR also covers this requirement.
  • Under CMDR (SOR/98-282), devices for investigational studies must be labeled per Section 86.
  • Canada is developing regulations and a UDI system to enhance safety, traceability, and quality, but it is still under development.

Puerto Rico

  • As a US territory, Puerto Rico follows all medical device labeling requirements established by the US FDA.

Europe

European Union

  • EU Member States recognize devices CE-marked per Regulation (EU) 2017/745.
  • Devices distributed in the EU must be CE-marked and labeled in compliance with Regulation (EU) 2017/745, Annex I, Chapter III, and in an official Union language determined by the Member State.
  • Regulation (EU) 2017/745 allows electronic user information for specific devices, with limitations outlined in Regulation (EU) 2021/2226.
  • The European Commission Directorate - General for Health And Food Safety provides guidance on language requirements in MDR language requirements for manufacturers Rev. 1 (March 2024).
  • This guide includes information on legal provisions and required languages for labeling, Declaration of Conformity, field safety notices, and conformity assessment documents.
  • The EU Commission has not harmonized ISO 20417, but it is in the process of doing so. Harmonization will align general labeling requirements with Regulation (EU) 2017/745, Annex I, Chapter III, 23.
  • IVD medical devices are regulated per Regulation (EU) 2017/746, Annex I, Chapter III, 20.
  • ISO 15223 may be used to present labeling elements via internationally recognized symbols instead of text.
  • All devices commercially distributed in the EU must be CE marked and have a UDI, per Regulation (EU) 2017/745, Article 27, and Regulation (EU) 2017/746, Article 24.
  • Applying a UDI facilitates device identification and traceability, optimizing supply chain traceability, combating counterfeiting, improving user safety, enhancing device recall capabilities, and improving monitoring by competent authorities.
  • Devices for investigational purposes must comply with the General Safety and Performance Requirements of Regulation (EU) 2017/745 and Regulation (EU) 2017/746, with exceptions to labeling elements like UDI application.

Non-European Union

  • Non-EU European countries may:
    • Recognize the CE marking of the EU
    • Require medical devices to be CE marked
    • Have their own regulations for medical devices
  • Countries that recognize the CE mark: Bosnia-Herzegovina, Kosovo, Moldova, Montenegro, and Serbia.
  • Countries that require the CE mark: Albania, Andorra, Belarus, Iceland, Liechtenstein, Monaco, Norway, and Switzerland.
  • Countries with their own regulations: Russia and Ukraine.
  • The MDR - language requirements for manufacturers Rev. 1 (March 2024) guide also specifies language requirements for non-EU countries.
  • In countries recognizing or requiring the CE mark, labeling must comply with the General Safety and Performance Requirements of Regulation (EU) 2017/745 and Regulation (EU) 2017/746, with potential country-specific requirements.
  • In countries that do not recognize the CE mark, labeling must comply with country-specific regulations.
    • Russia: Regulations listed in Table 10-5:
      • GOST R 50444-92: Medical Devices, Apparatuses and Equipment. General specifications
      • GOST R ISO 15223-1: Medical devices. Symbols to be used with medical device labels, labelling, and information to be supplied. Part 1. General requirements
      • GOST R ISO 15223-2: Medical devices. Symbols to be used with medical device labels, labelling, and information to be supplied. Part 2. Symbol development, selection and validation
      • The Law of the RF No. 2300-1 dated 7 February 1992 On the protection of consumers' rights
      • Resolution of the Government of the Russian Federation No. 1037 dated 15 August 1997 On actions to ensure the availability of information written in Russian on non-food goods imported into the Russian Federation
      • GOST R ISO 18113: In vitro diagnostic medical devices. Information supplied by the manufacturer (labeling)
    • Ukraine: Technical Regulation on medical devices, approved by Resolution of Cabinet of Ministers of Ukraine No. 753 dated 02.10.2013.
  • For investigational studies, labeling must comply with the country's regulations. Countries recognizing or requiring the CE mark typically have similar requirements to Regulation (EU) 2017/745 and Regulation (EU) 2017/746 but may have additional elements.

United Kingdom

  • The UK, including England, Scotland, Wales, and Northern Ireland, is transitioning to its own medical device and IVD regulations since withdrawing from the EU in 2020.
  • The Medicines and Healthcare Products Regulatory Agency (MHRA) will continue to recognize the CE marking until June 2030.
  • After this date, manufacturers must obtain UK Conformity Assessed (UKCA) marking to market products in the UK, except for Northern Ireland, which has no plans to require UKCA marking.
  • All devices in the UK must be labeled in English; Wales requires labeling in both English and Welsh.
  • As of April 2024, regulations closely mirror the EU Directives, now replaced by Regulation (EU) 2017/745 and Regulation (EU) 2017/746. New UK regulations are expected in July 2025.

Asia

China

  • Labeling is regulated by the National Medical Products Administration (NMPA) through Decree No. 6 – Regulation on Instructions for Use and Labels of Medical Devices and Decree of the State Council No. 739 - Regulations on the Supervision and Administration of Medical Devices.
  • In Hong Kong, labeling is governed by GN-01:2024-1(E), Section 4.4.13, requiring special listing information.
  • Investigational devices are regulated under China Good Clinical Practice No. 2022/28 - Guidelines for Medical Devices, requiring good quality labeling and appropriate language.
  • All devices must be labeled in Chinese.
  • The standard YY/T 0466.1:2007 - Symbols to be used with medical device labels, labelling and information to be supplied. Part 1: General requirements governs use of symbols.
  • The NMPA issued the Rules for Unique Identification System for Medical Devices in 2019, initiating a phased UDI implementation extending into 2024, enhancing user safety and device management.

Japan

  • Labeling for both investigation and commercial distribution is regulated by the Ministry of Health, Labor and Welfare through the Pharmaceuticals and Medical Devices Act, Articles 52 and 63 of the Japanese Act on Securing Quality, Efficacy, and Safety of Products, Including Pharmaceuticals and Medical Devices; IVD labeling is regulated by Article 41-3 of the same Act.
  • Local labeling must be on package inserts and meet regulatory requirements.
  • All devices must be labeled in Japanese.
  • As of December 2023, all medical devices must have a UDI entered into the Japan Medical Devices Information System.

India

  • Chapter VI of the Medical Devices Rules of 2017 outlines required labeling elements for medical devices and IVDs.
  • Investigational devices must also comply with these rules.
  • All devices must be labeled in English, with potential additional requirements for other languages based on region and target market.
  • Device labeling may use symbols recognized by the Bureau of Indian Standards or ISO.
  • The requirement for UDI assignment is covered under Chapter VI of the regulation.

South Korea

  • Labeling is governed by Articles 20-23 of the Medical Device Act and the Regulations on Labeling and Description of Medical Devices (2020), established by the Ministry of Food and Drug Safety (MFDS).
  • These articles also define the requirement for UDI assignment.
  • Medical devices used for investigational trials must comply with labeling elements in Articles 20-23.
  • Article 23 requires labeling descriptions in Articles 20-22 to be written accurately in Korean.
  • Device labels and accompanying information must be printed in Korean.
  • Instructions for use must comply with Article 7.

Latin America

Mexico

  • Labeling is regulated through the Official Mexican Norm, NOM-137-SSA1-2024, established by Comisión Federal para la Protección contra Riesgos Sanitarios (COFEPRIS).
  • NOM-137-SSA1-2024 aligns Mexico's requirements with international regulations, such as those of the US FDA, EU Regulations, and IMDRF guidelines.
  • All devices must be labeled in Spanish.
  • The updated regulation NOM-137-SSA1-2024 also contains updated symbols.
  • Currently, UDI assignment is not required.

Brazil

  • Medical devices are regulated through RDC 751/2022, while IVDs are regulated through RDC 830/2023, subjecting them to different labeling regulations.
  • Chapter 6 of RDC 751/2022 outlines requirements for device labeling, while Article 48 provides requirements for instructions for use.
  • Articles 47-50 of RDC 830/2023 provide requirements for IVD labeling.
  • Both regulations allow the use of symbols recognized by technical standards or defined in accompanying instructions.
  • All devices must be labeled in Brazilian Portuguese.
  • Devices intended for clinical investigations are exempt from notification and registration.
  • RDC 591/2021 outlines requirements for UDI assignment and application, with a phased implementation from June 2023 to January 2027.

Colombia

  • The National Food and Drug Surveillance Institute (INVIMA) regulates medical devices through Decree 4725/2005 and IVDs through Decree 3770/2004.
  • Chapter VIII of Decree 4725/2005 provides required labeling elements for medical devices.
  • Chapter I of Decree 3770/2004 provides required labeling elements for IVDs.
  • All devices must be labeled in Colombian Spanish.
  • Both regulations allow the use of symbols recognized by technical standards or defined in accompanying instructions.
  • INVIMA has begun implementing UDI assignment and registration, requiring UDI assignment to all classes of devices by February 2026.

Oceania

Australia

  • Labeling is regulated by the Australian Therapeutic Goods Administration (TGA) under the Therapeutic Goods (Medical Devices) Regulations 2002, Essential Principle 13 of Schedule 1, and TGA guidance.
  • All devices must be labeled in English.
  • Symbols may be used in place of text when recognized by technical standards or defined in accompanying instructions.
  • TGA announced in 2023 that they would soon begin to require compliance with registering the UDI associated with their commercially distributed devices in the AusUDID database.
  • Compliance with UDI requirements is not yet required, pending the release of revisions to the TGA Medical Device Regulations.

New Zealand

  • Medical devices are regulated by the New Zealand Medicines and Medical Devices Safety Authority (MedSafe) through the Medicines Act 1984, while IVDs are regulated through the Medicines Act 1981.
  • Part 4 of the Medicines Act 1984 provides required labeling elements for medical devices.
  • Section 44 of the Medicines Act 1981 provides required labeling elements for IVDs.
  • All devices must be labeled in English.
  • MedSafe recognizes ISO 15223 and encourages its use.
  • While MedSafe does not currently require UDI application, it is anticipated they will eventually require UDI assignment and registration.

Application of Regulations, Standards, and Guidance Documents to Device Labeling

  • Manufacturers of medical devices and IVDs must adhere to the requirements for commercial and investigational labeling.
  • Tables 11-6 and 11-7 summarize all requirements across various labeling levels.
  • Manufacturers may elect to claim conformance to ISO standards or follow the guidance of IMDRF/GRRP WG/N52.
  • Labeling elements are not required on every level, with exceptions found in corresponding regulations, standards, and guidances.
  • When labeling elements do not apply, manufacturers must provide a justification for their exclusion.

Upcoming/Proposed Changes in Regulations, Standards, and Guidance Documents

  • The global landscape of medical device regulations has experienced significant changes and is projected to undergo substantial changes in the coming years.

Canada

  • Canada is actively working to establish a database for UDI and the associated regulations to align their regulations with international medical device requirements and to promote enhanced safety, traceability, and quality of the medical devices introduced to their market.

Europe

  • Since the decision to withdraw from the EU in 2020, the UK's regulatory agency, the MHRA, has been working to establish its regulations for medical devices and IVDs.
  • However, this is not projected to be completed until July 2025.

Asia

  • NMPA announced in 2019 that a pilot program would begin to initiate the implementation of requirements for UDI.
  • Due to taking an approach to gradually phase in the requirements of UDI, the projected completion of this program is not scheduled to be completed until 2024.

Latin America

Mexico
  • As of April 2024, COFEPRIS is revising the Official Mexican Norm, NOM-137-SSA1-2024, with a planned publication date of July 2024.
Brazil
  • According to ANVISA Public Consultation 1051/2021, the regulator plans a 6-year rollout of UDI requirements to boost the traceability and monitoring of medical devices and equipment commercialized in Brazil.
  • With the implementation of RDC 591/2021, ANVISA began a phased implementation in June of 2023, with a targeted completion date of January 2027.

Oceania

Australia
  • In 2023, TGA announced that they would soon begin to require compliance with UDI requirements; however, this is not expected to start until the revisions to the TGA Medical Device Regulations are complete.
  • As of April 2024, the updates to the TGA Medical Device Regulations have not yet been released; however, the TGA is actively working on the updates to the TGA Medical Device Regulations and the framework for UDI.

Conclusion

  • The global medical device industry is evolving rapidly, with increasing scrutiny of medical devices.
  • Device manufacturers must prioritize accurate and compliant labeling to prevent delays and product recalls.
  • This chapter provided a summary of regulations governing medical device labeling, explained how to apply regulations with standards and guidances, and identified upcoming changes.