Product Labeling Requirements

Published by Steven Niedelman

Question: How do product labeling requirements differ between medical devices and pharmaceuticals?

Answer: The FDA has stringent regulations regarding the labeling of medical devices and pharmaceuticals.1 The principle difference in the labeling requirements between medical devices and pharmaceuticals is the comparative complexity of the requirements. While makers of both products must craft labeling in accord with FDA regulations as to the provision of certain information (e.g., name and place of manufacturer) and the withholding of other information (e.g., off-label uses), the required information for pharmaceuticals is more finite than the diverse landscape of medical devices allows. Pharmaceutical labeling requirements are the same across drugs, regardless of their intended treatment and only varying slightly depending on whether they are obtained by prescription or available over-the-counter. In contrast, given the heterogeneity of medical devices and the myriad different devices on the market, appropriate labeling may differ significantly among devices and is largely dependent on what environment the devices will be used. For example, as opposed to medical devices for which instructions for use are an integral part of labeling and vary widely by device, prescription drugs are generally taken orally and though dosage may vary, instructions for use are generally unnecessary. Accounting for this, the FDA has required a litany of very specific information to appear in all the labeling of all drugs and biologics, and has left more room for discretion in the labeling of medical devices.

The requirements for prescription drug labeling can be found in 21 CFR Part 201.2Prescription drug labeling must meet three general requirements. Specifically, the labeling must:

contain a summary of essential scientific information needed for the safe and effective use of the drug;
be informative and accurate and neither promotional in tone nor false or misleading in any particular; and
be based whenever possible on data derived from human experience.

The “essential scientific information” the first requirement refers to includes a statement of identity, a declaration of net quantity of contents, and a statement of dosage. It is also important to note that these requirements are ongoing for the life of the product, and not just at the time of bringing the drug to market. That is, in order to be in accord with the second requirement, “the labeling must be updated when new information becomes available that causes the labeling to become inaccurate, false, or misleading.” (21 CFR § 201.56(a)(2).) Furthermore, the FDA-approved patient labeling must be reprinted following the prescription drug labeling or accompany the prescription drug labeling. This labeling information, detailed in 21 CFR 201.57, includes highlights of prescribing information followed by full prescribing information. Full prescribing information includes: (1) boxed warning; (2) indications and usage; (3) dosage and administration; (4) dosage forms and strengths; (5) contraindications; (6) warnings and precautions; (7) adverse reactions; (8) drug interactions; (9) use in specific populations (e.g., pregnant woman, children, and the elderly); (10) drug abuse and dependence; (11) information on overdosage; (12) description; (13) clinical pharmacology; (14) nonclinical toxicology; (15) clinical studies; (16) references; (17) how supplied/storage and handling; and (18) patient counseling information. Format requirements can be found in 21 CFR § 201.57(d).

For medical devices, labeling requirements are found in 21 CFR Part 801. First, like drugs, the label of a device in package form shall specify conspicuously the name and place of business of the manufacturer, packer, or distributor. Next, the labeling must contain a statement of intended uses. The intended uses “refer to the objective intent of the persons legally responsible for the labeling of devices.” (21 CFR § 801.4.) The next requirement of adequate labeling of medical devices is for the inclusion of adequate directions for use. The FDA defines these as "directions under which the layman can use a device safely and for the purpose for which it is intended." If applicable, such instructions for use should include:

statements of all conditions, purposes, or uses for which such device is intended, including conditions, purposes, or uses for which it is prescribed, recommended, or suggested in its oral, written, printed, or graphic advertising, and conditions, purposes, or uses for which the device is commonly used;
quantity of dose, including usual quantities for each of the uses for which it is intended and usual quantities for persons of different ages and different physical conditions;
frequency of administration or application;
duration of administration or application;
time of administration or application, in relation to time of meals, time of onset of symptoms, or other time factors;
route or method of administration or application; and
preparation for use, i.e., adjustment of temperature, or other manipulation or process.

The prominence of the required label standards is dealt with in 221 CFR § 801.15.

A medical device is considered misbranded if (a) its labeling is false or misleading in any particular; and unless (b) its label bears, to the exclusion of any other nonproprietary name, its established name, prominently printed in type at least half as large as that used thereon for any proprietary name; and (c) its labeling bears adequate instructions for use and such adequate warnings against use in those pathological conditions or by children where its use may be dangerous to health, or against unsafe dosage or methods or duration of administration or application, in such manner and form, as are necessary for protection of users.

Unlike pharmaceuticals which are typically used directly by consumers either orally or by other means, many devices are designed solely for physicians based on their education, training and experience to treat patients correctly, such as x-ray machines, excimer laser, endoscopes, among many others. Adequate directions for such devices could not be written for safe lay use. In those situations, device manufacturers are exempt from providing adequate directions for safe lay use by complying with the prescription device labeling requirements in 21 CFR 801.109. Prescription devices other than surgical instruments, must bear 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 he practices to use or order the use of the device;

Prescription devices must still bear identifying label information, but their instructions for use provides information suitable for use by physicians to properly treat patients with devices. Some prescription devices as well have a consumer element, such as prescription contact lenses that will require labeling for physicians regarding proper indications and fitting, also labeling for the consumer about the care and use of their lenses. In those situations, manufacturers must consider labeling designed for proper use by the healthcare professional, as well as labeling designed for understanding by the layman on how to care for or properly use their prescription device.

As healthcare in the United States increasingly shifts away from healthcare facilities, more and more devices traditionally used in hospital settings are being used in home healthcare environments. This may present challenges for some manufacturers who are now faced with providing adequate directions for safe lay use of devices that may have not been designed with the consumer in mind.

In addition to the regulations set forth in 21 CFR Part 801 on medical device labeling, the FDA has provided several guidance documents to assist with the drafting of medical device labels and accompanying instructions for use. These include: (1) Write it Right: Recommendations for Developing User Instruction Manuals for Medical Devices Used in Home Health Care, August 1993; (2) Device Labeling Guidance #G91-1, 1991; and (3) Human Factors Principles for Medical Device Labeling, September 1993.

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[1] “Labeling” as it is used here (and by the FDA) is a broad term and is inclusive of, for example, brochures, pamphlets, and “Dear Doctor” letters.

[2] The requirements for over-the-counter drugs vary slightly and can be found in 21 CFR 201.60-80.

Steven Niedelman serves as lead quality systems and compliance consultant to the FDA & Life Sciences practice team at the law firm of King & Spalding.

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