Labelling and promoting a device in the United States
In the United States a device's label is what is on it and its labelling is everything else, advertising included, and the rules on device promotion are far less explicit than a medicine's. A device is cleared for the use its labelling states, and a name, an advertisement, a website or a hyperlink that suggests another use can leave it misbranded or in breach of the labelling regulations. The abbreviation IFU stands for three different things.
Regulators of device labelling and advertising
The FDA regulates device labelling under the Federal Food, Drug, and Cosmetic Act, but it regulates advertising in partnership with the Federal Trade Commission (FTC), the agency that stops unfair, deceptive or fraudulent practices in the marketplace. Two device-labelling writers judged in 2019 that knowing which agency to contact confuses and frustrates consumers and companies alike, and that even the FDA has difficulty keeping up with the new issues that arise every day.
Label and labelling
Put simply, anything on the device, attached to the unit, box, case, package or wrapper, is the label, and everything else, including the Instructions for Use, promotion and advertising, is labelling.
An appellate court held that most, if not all, advertising is labelling, because the Act defines labelling as all printed matter accompanying any article and Congress did not exclude advertising from that definition. Because advertising is treated as accompanying material, the FDA regards any bias shown toward a product as advertising or promotion, and so as labelling, and depending on the device's class or risk the advertising comes under the scrutiny of the FTC as well as the FDA.
The three meanings of IFU
IFU is used for three different things, and they are not interchangeable. Instructions for Use is any means a manufacturer uses to convey how to use the device safely and effectively, such as directions on the back of a Tyvek pouch, printing on the shaft of an instrument, printed material in the box or packaging, a quick-start guide, or an instruction or training video. Indications for Use, the sense also common in pharmaceuticals, means the reasons or situations in which a device should be used. A product's intended use is sometimes called Intended for Use, perhaps because the statement of intended use has to sit at the front of the Instructions for Use, operator's manual or user manual. The statement of intended use is not an IFU, however, but a regulatory tenet: it states what the label, and the FDA, say the device is used for.
Device labelling compared with drug labelling
Strict and rigorous naming and labelling conventions govern drugs and biologics, but no such clear-cut conventions exist for devices, so in labelling methodology the two have few similarities. In the view of two device-labelling writers in 2019, the device labelling regulations have limitations because they are tailored not to specific device indications but to the vague and varying notion of intended use.
Device promotion differs from drug promotion most noticeably in the absence of decisive regulation, and also in the product life cycle and how often products are modified, in manufacturers' interactions with health care providers, in the need for product training and in reimbursement methods. As of 2019, apart from the appellate ruling that advertising is labelling, FDA guidance on device advertising was minimal, whereas 21 CFR Part 202 set extensive and detailed requirements and prohibitions for drug advertising. The promotional guidance for devices was limited and far less explicit than 21 CFR Part 202, and the proactive requirements that apply to drugs did not necessarily apply to device promotion.
Set side by side in an illustrative comparison that is not all-inclusive and is subject to change and interpretation, drug and device labelling requirements differ as follows. The naming authorities for drugs are the Office of Prescription Drug Promotion and the Division of Medication Error Prevention and Analysis, and for devices there is none. A drug's name cannot be changed, while a device's can, through the FDA's Federal Unified Registration and Listing System. A drug label carries a National Drug Code with the address and contact information, and a device label carries the address and contact information. Indications for use and intended use are on a drug's label, and selection-for-use testing and warnings, precautions and contraindications are required. For a device, indications for use, selection-for-use testing and warnings, precautions and contraindications are optional, some of them depending on the risk level, and a statement of intended use within the Instructions for Use may be required, depending on the risk class (Class I, II, III or unclassified).
Device regulation has historically trailed drug regulation, and labelling is no exception. Two device-labelling writers hoped in 2019 that drug practices such as full disclaimers, public advertising disclosures of probable side effects, and conditions of use would come to apply to devices, and saw the greatest challenge for devices as the massive range of products and technologies that require regulation. In their view the FDA must also keep up with new device technologies and their ever-evolving terminology, and whether it can remained to be seen.
Benefit terms graded by risk class
Without black box warnings or full disclosure of potential side effects, device companies advertise higher-risk products with yellow-zone terms that describe or imply clinical benefits, based on the device's classification, or risk. Take Device X, a Class II phototherapy device that kills certain acne-causing bacteria on the skin. Describing it as a cure for acne would be red zone, because the statement is inaccurate and deceptive and breaches labelling regulation. Treat, as in Device X is used to treat acne, is an improved, yellow-zone term. Manage, as in Device X may be used to manage mild to moderate acne, is a green-zone term, the ideal standard for device promotion, because that sentence is accurate, truthful and unlikely to cause harm.
Intended use and misbranding
The FDA approves or clears a product for the specific intended use its labelling describes. Where the evidence shows that a company's actual intended use differs from it, the product is deemed misbranded, which can lead to civil or criminal penalties.
Under section 502 of the Act, misbranding occurs when advertising or promotion, labelling and naming included, is false or misleading in any way. It also occurs when a label lacks required information, such as the generic name in type at least half the size of the trade name, an abbreviated statement of intended use, a description of the device's components, and its warnings, contraindications, side effects and cautionary statements.
Device names
A device's name is also its label. Device naming is discretionary, however, and with no foundational metrics, wide and unclear boundaries and a gargantuan product range, it is a matter of the subjectivity of the review panel of the Center for Devices and Radiological Health (CDRH) and of its inference of implied claims. For example, names such as TumorBuster and NeuroCure did not receive CDRH approval, and the most evident of the issues raised was that they suggest an intended use, to cure, mitigate or treat a diseased or damaged state, whatever the validity of the claim. Innovation in device technology, and the vocabulary generated to describe it, outpace the ability of regulators to establish a naming methodology, but a name is still a label and so can be false, misleading or even a threat to public health.
A drug name such as ViraCalm would be disallowed without acceptable clinical data supporting the inference of viral inactivation, yet the FDA cleared a device of that name, described as the world's first non-invasive, zero side-effects treatment device for genital herpes, although no such indication or supporting data existed. The device had been cleared for the symptomatic relief and management of chronic intractable pain and the adjunctive treatment of post-surgical and post-traumatic pain. In 2012 the CDRH sent its maker, NeuroMed Devices, a warning letter for claims outside the device's cleared use. The CDRH had earlier asked, and the company had agreed, to revise the name to remove any implied reference to the treatment of herpes, and had asked it to remove genital herpes from the indications for use; the letter concluded that the claims on the company's website rendered the device misbranded and adulterated.
Hyperlinks and other published statements
A company that links to sites promoting off-label use of its devices, through unevaluated clinical benefits or unsubstantiated claims, misleads its customers and breaches device labelling regulations, which can lead to disciplinary action from the FDA, the FTC or both. More generally, a drug or device company may not make statements that are incorrect or create a false impression, intentionally or not, in its advertising, its packaging or any product information it publishes, testimonials on websites and social media included. Whether the sponsor intended to mislead makes no difference: any representation that creates a misleading impression breaches labelling regulations.
FDA and FTC review of device promotion
The FDA reviews device advertising and promotion by reading the labelling and any publicly available information from any source. Its compliance reviewers read journal articles, periodicals and product web pages and search the internet for how companies describe their devices and how consumers use them, and they attend trade shows and conferences to hear how company representatives explain and promote a device's intended use, giveaways included. An FDA agent can also visit a company's facilities for inspection at any time and without warning. The agency sets its enforcement priorities by risk, so the riskier the product, the more attention it receives and the tighter its enforcement. It works with the FTC's consumer protection arm to monitor device advertising whatever the class, but promotion of experimental or investigational devices, and of approved products for off-label use, which the FDA views as misbranding, is strictly prohibited.