Label还是Labeling？美国FDA医疗器械Labeling法规解读
📅 2024年07月31日
📂 注册解析
✍️ Grzan
国瑞中安是一家集检测、临床试验及注册咨询的一站式综合服务商，在以往辅导客户的过程中很多企业并不清楚label和labeling，对其相关法规也不清楚。大家都知道标签、说明书资料对产品来说至关重要，也是在注册过程中审核老师比较关注的资料，今天小编就给大家梳理了美国FDA的相关要求，希望可以协助行业朋友解决一些疑惑。
1) Label and labeling定义
Label 定义-Federal Food, Drug and Cosmetic Act (FFDCA) section 201(k):
-“display of written, printed, or graphic matter upon the immediate container of any article”
-The term ‘immediate container’ does not include package liners. Any word, statement, or other information appearing on the immediate container must also appear ‘on the outside container or wrapper, if any there be, or the retail package of such article, or is easily legible through the outside container of wrapper.’
Labeling定义-Section 201(m):
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’ at any time while a device is held for sale after shipment or delivery for shipment in interstate commerce.
-The term ‘accompanying’ is interpreted liberally to mean more than physical association with the product. It extends to posters, tags, pamphlets, circulars, booklets, brochures, instruction books, direction sheets, fillers, etc. ‘Accompanying’ also includes labeling that is brought together with the device after shipment or delivery for shipment in interstate commerce.
从上述定义可知Label是指任何物品直接容器上的书面、印刷或图形资料，而Labeling是指包含label在内的说有伴随产品的书面、印刷或图形材料，如说明书，手册、运输包装等；
注：Labeling包含Label；通常Label 翻译成标签，labeling可以翻译成产品介绍材料。
介绍了Label和labeling定义后，我们来看下FDA对其都有什么样的法规要求呢？
2) FDA labeling 相关法规要求
| 序号 | 法规名称及编号 | 网址 | 备注 |
| 1 | Labeling-Regulatory Requirements for Medical Devices | https://www.fda.gov/media/74034/download | Labeling法规要求 |
| 2 | Device Labeling Guidance #G91-1 (Blue Book Memo) | https://www.fda.gov/regulatory-information/search-fda-guidance-documents/device-labeling-guidance-g91-1-blue-book-memo | 设备标签指南（蓝皮书） |
| 3 | Guidance on Medical Device Patient Labeling; Final Guidance for Industry and FDA Reviewers | https://www.fda.gov/media/71030/download | 针对OCT产品可参考的labeling 法规 |
| Design Considerations for Devices Intended for Home Use | https://www.fda.gov/regulatory-information/search-fda-guidance-documents/design-considerations-devices-intended-home-use | ||
| Labeling Requirements – Over-The-Counter (Non-Prescription) Medical Devices | https://www.fda.gov/medical-devices/general-device-labeling-requirements/labeling-requirements-over-counter-non-prescription-medical-devices | ||
| 4 | Reprocessing Medical Devices in Health Care Settings: Validation Methods and Labeling | https://www.fda.gov/regulatory-information/search-fda-guidance-documents/reprocessing-medical-devices-health-care-settings-validation-methods-and-labeling | 医疗保健环境下医疗器械的再处理:验证方法和标签（可重复产品） |
| 5 | 21 CFR 801 LABELING | https://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfCFR/CFRSearch.cfm?CFRPart=801 | 医疗器械标签通用要求 |
| 6 | 21 CFR 809 IN VITRO DIAGNOSTIC PRODUCTS FOR HUMAN USE | https://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfCFR/CFRSearch.cfm?CFRPart=809 | 针对IVD产品 |
| 7 | 21 CFR 812 INVESTIGATIONAL DEVICE EXEMPTIONS21 CFR 812.5 Labeling of investigational devices. | https://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfCFR/CFRSearch.cfm?CFRPart=812 | 针对IDE产品 |
| 8 | 21 CFR 830UNIQUE DEVICE IDENTIFICATION | https://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfCFR/CFRSearch.cfm?CFRPart=830 | UDI要求 |
| 9 | 21 CFR 820.120 Device labeling21 CFR 820.130 Device packaging. | https://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfCFR/CFRSearch.cfm?CFRPart=820 | Labeling 控制要求 |
| 10 | 21 CFR 1010 PERFORMANCE STANDARDS FOR ELECTRONIC PRODUCTS: GENERAL | https://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfCFR/CFRSearch.cfm?CFRPart=1010 | 针对电子产品 |
备注：
1）以上仅为重点列举分享
2）针对不同类型的产品可以参考的法规会对应有所变化，所以企业朋友需要针对自己产品的类型选择适合的标签，比如一款IVD产品，我们肯定重点要参考的是21 CFR 809中的标签要求。
下面也给大家分享下21 CFR 809 Subpart B – Labeling的内容：
3) 21 CFR 809 Subpart B – Labeling 809.10 Labeling for in vitro diagnostic products
| Subpart B – Labeling 809.10 Labeling for in vitro diagnostic products. IVD 标签 | (a) The label for an in vitro diagnostic product shall state the following information, except where such information is not applicable, or as otherwise specified in a standard for a particular product class or as provided in paragraph (e) of this section. Section 201(k) of the act provides that “a requirement made by or under authority of this act that any word, statement, or other information appear on the label shall not be considered to be complied with unless such word, statement, or other information also appears on the outside container or wrapper, if any there be, of the retail package of such article, or is easily legible through the outside container or wrapper.” | 体外诊断产品的标签应注明以下信息，除非此类信息不适用，或者在特定产品类别的标准中另有规定，或者如本节第(e)段所述。该法案第201(k)条规定:“除非此类文字、陈述或其他信息也出现在此类产品的零售包装的外容器或外包装上，或者通过外容器或外包装可以清晰地看到，否则不得认为符合本法案规定的要求，即任何文字、陈述或其他信息都应出现在标签上。 |
| (1) The proprietary name and established name (common or usual name), if any. | 1) 专有名称和既定名称(通用名称或惯用名称)(如有) | |
| (2) The intended use or uses of the product. | 2) 产品的预期用途。 | |
| (3) For a reagent, a declaration of the established name (common or usual name), if any, and quantity, proportion or concentration of each reactive ingredient; and for a reagent derived from biological material, the source and a measure of its activity. The quantity, proportion, concentration, or activity shall be stated in the system generally used and recognized by the intended user, e.g., metric, international units, etc. | 3) 对于试剂，应声明每种反应成分的名称(通用名称或常用名称)、数量、比例或浓度(如有的话);对于从生物材料衍生的试剂，应声明其来源和活性度量。数量、比例、浓度或活性应以预期用户普遍使用和认可的度量单位表示，例如标准度量单位、国际单位等。 | |
| (4) A statement of warnings or precautions for users as established in the regulations contained in 16 CFR part 1500 and any other warnings appropriate to the hazard presented by the product; and a statement “For In Vitro Diagnostic Use” and any other limiting statements appropriate to the intended use of the product. The limiting statement appropriate to the intended use of a prescription in vitro diagnostic product shall bear the symbol statement “Rx only” or “RX only” or the statement “Caution: Federal law restricts this device to sale by or on the order of a ___”, the blank to be filled with the word “physician”, “dentist”, “veterinarian”, or with the descriptive designation of any other practitioner licensed by the law of the State in which the practitioner practices to use or order the use of the device. | 4) 规定的用户警告或预防措施声明，以及与产品所含危害性相适应的任何其他警告; 及“For In Vitro Diagnostic Use”声明、与产品预期用途相适应的任何其他限制性声明、与处方体外诊断产品的预期用途相适应的限制性声明应带有“Rx only”或“RX only”的符号声明； 或:联邦法律限制该设备“Caution: Federal law restricts this device to sale by or on the order of a_”的声明，空格处填写physician”(医牛)、“dentist”(牙医)、“veterinarian(兽医)，或填写根据执业所在州的法律获得执业许可的任何其他执业者的描述性名称，以使用或订购使用该设备。 | |
| (5) For a reagent, appropriate storage instructions adequate to protect the stability of the product. When applicable, these instructions shall include such information as conditions of temperature, light, humidity, and other pertinent factors. For products requiring manipulation, such as reconstitution and/or mixing before use, appropriate storage instructions shall be provided for the reconstituted or mixed product which is to be stored in the original container. The basis for such instructions shall be determined by reliable, meaningful, and specific test methods such as those described in § 211.166 of this chapter. | 5) 对于试剂，适当的储存说明，足以保护产品的稳定性。在适用的情况下，这些指示应包括诸如温度、光照、湿变等条件和其他相关因素的信息。对于需要操作的产品，如使用前的重组和/或混合，应提供适当的储存说明，用于诸存在原容器中的重组或混合积。此类指令的依据应由可靠、有意义和特定的测试方法来确定 | |
| (6) For a reagent, a means by which the user may be assured that the product meets appropriate standards of identity, strength, quality and purity at the time of use. This shall be provided, both for the product as provided and for any resultant reconstituted or mixed product, by including on the label one or more of the following: | 6) 对于试剂，一种使用户能够确信产品在使用时符合适当的特性、强度、质量和纯度标准的方法。对于所提供的产品和由此产生的任何再生或混合积，应在标签上包括以下一项或多项内容: | |
| (i) An expiration date based upon the stated storage instructions. | (i)根据所述储存指示确定的有效期。 | |
| (ii) A statement of an observable indication of an alteration of the product, e.g., turbidity, color change, precipitate, beyond its appropriate standards. | (ii)一份声明，说明产品有明显超出其适当标准的变化，例如混浊度、颜色变化、沉淀物 | |
| (iii) Instructions for a simple method by which the user can reasonably determine that the product meets its appropriate standards. | (iii)说明一种简单的方法，使用户可以合理地确定该产品符合其适当的标准。 | |
| (7) For a reagent, a declaration of the net quantity of contents, expressed in terms of weight or volume, numerical count, or any combination of these or other terms which accurately reflect the contents of the package. The use of metric designations is encouraged, wherever appropriate. If more than a single determination may be performed using the product, any statement of the number of tests shall be consistent with instructions for use and amount of material provided. | 7) 对于试剂，应声明其组分净含量，以重量或体积表示，或以数字计数，或以这些或其他准确反映包装内含量的术语的任何组合表示。在适当情况下，应鼓励使用公制名称。如果可以使用该产品进行多次测定，则测试次数的说明应与使用说明和提供的材料量一致。 | |
| (8) Name and place of business of manufacturer, packer, or distributor. | (8) 制造商、包装商、经销商的名称、营业场所。 | |
| (9) A lot or control number, identified as such, from which it is possible to determine the complete manufacturing history of the product. | (9) 可据此确定产品的完整制造历史的批号或控制编号。 | |
| (i) If it is a multiple unit product, the lot or control number shall permit tracing the identity of the individual units. | (i)如果是多单元产品，批号或控制号应允许识别到单个单元。 | |
| (ii) For an instrument, the lot or control number shall permit tracing the identity of all functional subassemblies. | (ii) 对于仪器，批号或控制号应允许识别所有功能性子组件。 | |
| (iii) For multiple unit products which require the use of included units together as a system, all units should bear the same lot or control number, if appropriate, or other suitable uniform identification should be used. | (iii)对于需要将所含单元作为系统一起使用的多单元产品，所有单元应酌情使用相同的批号或控制号，或使用其他适当的统一标识。 | |
| (10) Except that for items in paragraphs (a) (1) through (9) of this section: (i) In the case of immediate containers too small or otherwise unable to accommodate a label with sufficient space to bear all such information and which are packaged within an outer container from which they are removed for use, the information required by paragraphs (a) (2), (3), (4), (5), (6) (ii), (iii) and (7) of this section may appear in the outer container labeling only. | 10) 就本节(a)(1)至(9)项所指的条款而言: (i)如果内包装太小，或因其他原因而无法容纳有足够空间载列所有此类资料的标签，且内包装还有外包装的情况下，则本节(a)(2)、(3)、(4)、(5)、(6)（ii）(iii) 和第(7)项所要求载列的资料，可仅在外容器标签上载列。 | |
| (ii) In any case in which the presence of this information on the immediate container will interfere with the test, the information may appear on the outside container or wrapper rather than on the immediate container label. | (ii)在任何情况下，如果内容器上的信息会干扰测试，则信息可以出现在外容器或包装上，而不是内容器标签上。 | |
| (b) Labeling accompanying each product, e.g., a package insert, shall state in one place the following information in the format and order specified below, except where such information is not applicable, or as specified in a standard for a particular product class. The labeling for a multiple-purpose instrument used for diagnostic purposes, and not committed to specific diagnostic procedures or systems, may bear only the information indicated in paragraphs (b) (1), (2), (6), (14), and (15) of this section. The labeling for a reagent intended for use as a replacement in a diagnostic system may be limited to that information necessary to identify the reagent adequately and to describe its proper use in the system. | （b）伴随每种产品的标签，例如包装说明书，应在一个地方用以下格式和顺序的列出以下信息，除非这些信息不适用或者按照特定产品类别的标准规定。对于用于诊断目的的多用途仪器，且不用于特定的诊断程序或系统，其标签可仅标明本节(b)(1)、(2)、(6)、(14)和(15)段所指明的信息。对于用作诊断系统替代品的试剂的标签其信息可仅限于足以识别该试剂并在系统中正确使用该试剂的信息。 | |
| (1) The proprietary name and established name, i.e., common or usual name, if any. | 1) 专有名称和既定名称(通用名称或惯用名称)(如有) | |
| (2) The intended use or uses of the product and the type of procedure, e.g., qualitative or quantitative. | 2) 产品的预期用途和程序类型，例如定性or 定量。 | |
| (3) Summary and explanation of the test. Include a short history of the methodology, with pertinent references and a balanced statement of the special merits and limitations of this method or product. If the product labeling refers to any other procedure, appropriate literature citations shall be included and the labeling shall explain the nature of any differences from the original and their effect on the results. | 3）测试的总结和说明。包括方法学简短历史，并附有相关参考资料，并对该方法或产品的特殊优点和局限性作出平衡的陈述。 如果产品标签提及任何其他程序，应包括适当的文献引文，标签应解释与原件的任何差异的性质及其对结果的影响。 | |
| (4) The chemical, physical, physiological, or biological principles of the procedure. Explain concisely, with chemical reactions and techniques involved, if applicable. | 4）测试原理: 测量程序的化学、物理、生理学或生物学原理。简明扼要地解释，包括所涉及的化学反应和技术(如果适用)。 | |
| (5) Reagents: | 5) 试剂： | |
| (i) A declaration of the established name (common or usual name), if any, and quantity, proportion or concentration or each reactive ingredient; and for biological material, the source and a measure of its activity. The quantity, proportion, concentration or activity shall be stated in the system generally used and recognized by the intended user, e.g., metric, international units, etc. A statement indicating the presence of and characterizing any catalytic or nonreactive ingredients, e.g., buffers, preservatives, stabilizers. | （i）已确定名称(通用名称或惯用名称)的声明(如果有的话)，以及数量、比例或浓度或每种活性成分;对于生物材料，其来源和活性的衡量标准。数量、比例、浓度或活性应以预期用户普遍使用和承认单位形式表示，例如公制、国际单位等。说明存在任何催化或非反应性成分(如缓冲剂、防腐剂、稳定剂)并说明其特征的声明。 | |
| (ii) A statement of warnings or precautions for users as established in the regulations contained in 16 CFR part 1500 and any other warnings appropriate to the hazard presented by the product; and a statement “For In Vitro Diagnostic Use” and any other limiting statements appropriate to the intended use of the product. The limiting statement appropriate to the intended use of a prescription in vitro diagnostic product shall bear the symbol statement “Rx only” or “RX only” or the statement “Caution: Federal law restricts this device to sale by or on the order of a ___”, the blank to be filled with the word “physician”, “dentist”, “veterinarian”, or with the descriptive designation of any other practitioner licensed by the law of the State in which the practitioner practices to use or order the use of the device. | (ii)规定的用户警告或预防措施声明，以及与产品所含危害性相适应的任何其他警告; 及“For In Vitro Diagnostic Use”声明、与产品预期用途相适应的任何其他限制性声明、与处方体外诊断产品的预期用途相适应的限制性声明应带有“Rx only”或“RX only”的符号声明； 或:联邦法律限制该设备“Caution: Federal law restricts this device to sale by or on the order of a_”的声明，空格处填写physician”(医牛)、“dentist”(牙医)、“veterinarian(兽医)，或填写根据执业所在州的法律获得执业许可的任何其他执业者的描述性名称，以使用或订购使用该设备。 | |
| (iii) Adequate instructions for reconstitution, mixing, dilution, etc. | (iii)关于复溶、混合、稀释等的适当说明。 | |
| (iv) Appropriate storage instructions adequate to protect the stability of the product. When applicable, these instructions shall include such information as conditions of temperature, light, humidity, and other pertinent factors. For products requiring manipulation, such as reconstitution and/or mixing before use, appropriate storage instructions shall be provided for the reconstituted or mixed product. The basis for such instructions shall be determined by reliable, meaningful, and specific test methods such as those described in 搂 211.166 of this chapter. | (iv)适当的储存说明，足以保护产品的稳定性。在适用的情况下，这些指示应包括诸如温度、光照、湿变等条件和其他相关因素的信息。对于需要操作的产品，如使用前的重组和/或混合，应提供适当的储存说明，用于诸存在原容器中的重组或混合积。此类指令的依据应由可靠、有意义和特定的测试方法来确定 | |
| (v) A statement of any purification or treatment required for use. | (v)使用所需的任何纯化或处理的说明。 | |
| (vi) Physical, biological, or chemical indications of instability or deterioration. | (vi)不稳定或恶化的物理、生物或化学迹象。 | |
| (6) Instruments: | 6) 仪器 | |
| (i) Use or function. | (i)使用或功能。 | |
| (ii) Installation procedures and special requirements. | (ii)安装程序和特殊要求。 | |
| (iii) Principles of operation. | (iii)操作原则。 | |
| (iv) Performance characteristics and specifications. | (iv)性能特点及规格: | |
| (v) Operating instructions. | (v)操作说明 | |
| (vi) Calibration procedures including materials and/or equipment to be used. | (vi)校准程序，包括将使用的材料和/或设备。 | |
| (vii) Operational precautions and limitations. | (vii)操作注意事项和局限性。 | |
| (viii) Hazards. | (viii\)危害。 | |
| (ix) Service and maintenance information. | (ix) 服务和维护信息。 | |
| (7) Specimen collection and preparation for analysis, including a description of: | (7)样本采集和分析准备，包括对下列事项的说明: | |
| (i) Special precautions regarding specimen collection including special preparation of the patient as it bears on the validity of the test. | (i)收集标本的特别预防措施，包括对病人的特殊准备，因为这对试验的有效性有影响。 | |
| (ii) Additives, preservatives, etc., necessary to maintain the integrity of the specimen. | (ii)保持标本完整性所必需的添加剂、防腐剂等。 | |
| (iii) Known interfering substances. | (iii)已知干扰物质。 | |
| (iv) Recommended storage, handling or shipping instructions for the protection and maintenance of stability of the specimen. | (iv)为保护和维持样本的稳定性而建议的储存、搬运或装运说明。 | |
| (8) Procedure: A step-by-step outline of recommended procedures from reception of the specimen to obtaining results. List any points that may be useful in improving precision and accuracy. | (8) 程序: 从接收样本到获得结果的建议程序具体步骤。列出任何有助于提高精确度和准确性的要点。 | |
| (i) A list of all materials provided, e.g., reagents, instruments and equipment, with instructions for their use. | (i)提供的所有材料清单，如试剂、仪器和设备并附有使用说明。 | |
| (ii) A list of all materials required but not provided. Include such details as sizes, numbers, types, and quality. | (ii)所有所需但未提供材料的清单，包括尺寸、数量、类型和质量等详细资料。 | |
| (iii) A description of the amounts of reagents necessary, times required for specific steps, proper temperatures, wavelengths, etc. | (iii)说明必要的试剂量、具体步骤所需的时间、适当的温度、波长等。 | |
| (iv) A statement describing the stability of the final reaction material to be measured and the time within which it shall be measured to assure accurate results. | (iv)说明待测最终反应物料的稳定性及为确保准确结果而应测定的时间的陈述。 | |
| (v) Details of calibration: Identify reference material. Describe preparation of reference sample(s), use of blanks, preparation of the standard curve, etc. The description of the range of calibration should include the highest and the lowest values measurable by the procedure. | (v)校准的细节：确定参考材料。描述参考样品的制备，空白的使用，标准曲线的制备等。校准范围的描述应包括该程序可测量的最高和最低值。 | |
| (vi) Details of kinds of quality control procedures and materials required. If there is need for both positive and negative controls, this should be stated. State what are considered satisfactory limits of performance. | (vi)质量控制程序和所需材料的详细情况。如果需要阴阳质控，应予以说明。说明什么是令人满意的性能限度。 | |
| (9) Results: Explain the procedure for calculating the value of the unknown. Give an explanation for each component of the formula used for the calculation of the unknown. Include a sample calculation, step-by-step, explaining the answer. The values shall be expressed to the appropriate number of significant figures. If the test provides other than quantitative results, provide an adequate description of expected results. | (9) 结果：解释计算未知值的过程。对用于计算未知值的公式的每个组成部分进行解释。包括一个样本计算，逐步解释答案。值应表示为适当的有效数字。如果试验提供非定量结果，则应提供对预期结果的充分描述。 | |
| (10) Limitation of the procedure: Include a statement of limitations of the procedure. State known extrinsic factors or interfering substances affecting results. If further testing, either more specific or more sensitive, is indicated in all cases where certain results are obtained, the need for the additional test shall be stated. | (10) 程序的局限性:包括程序的局限性说明、说明影响结果的已知外部因素或干扰物质。如果所有获得特定结果的病例都表明需要更具体或更敏感的进一步测试，则应说明进行额外测试的必要性。 | |
| (11) Expected values: State the range(s) of expected values as obtained with the product from studies of various populations. Indicate how the range(s) was established and identify the population(s) on which it was established. | (11) 预期值(参考区间): 说明从各种人群的研究中获得的预期值的范围。说明范围是如何建立的，并确定其建立的基础人群。 | |
| (12) Specific performance characteristics: Include, as appropriate, information describing such things as accuracy, precision, specificity, and sensitivity. These shall be related to a generally accepted method using biological specimens from normal and abnormal populations. Include a statement summarizing the data upon which the specific performance characteristics are based. | (12)具体性能特征: 酌情包括描述准确度、精密度、特异度和敏感度等信息，并与使用来自正常和异常人群的生物标本的公认方法相关联。包括总结具体性能特征所依据的数据的声明。 | |
| (13) Bibliography: Include pertinent references keyed to the text. | (13) 参考文献: 包括与正文相关的参考文献。 | |
| (14) Name and place of business of manufacturer, packer, or distributor. | (14)制造商、包装商或分销商的名称和营业地点。 | |
| (15) Date of issuance of the last revision of the labeling identified as such. | (15) 标签最新版本及其签发日期 |
备注：本次内容仅分享常规的情况，特殊产品如ASR，OTC test sample collection systems for DOA的要求如您有需求可以联系国瑞中安进行详细咨询。
