Unapproved and off-label use of drugs and devices: What dermatologists need to know

Legally Speaking

Rob Portman

Rob Portman is a health care attorney with Powers Pyles Sutter & Verville in Washington, D.C., and serves as General Counsel for the AAD and AADA.

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The Food and Drug Administration (FDA) regulates the safety and effectiveness of drugs and devices and approves these products for specific uses, purposes, or indications. To secure FDA approval for a drug or medical device, a manufacturer must demonstrate that its product is safe and effective for each of its intended uses. While the FDA does not directly regulate the practice of medicine, physicians may not use or advertise the use of unapproved drugs or devices except in very limited circumstances. By contrast, the so-called “practice of medicine” exception does permit physician “off-label” use of drugs and devices that have been approved for at least one indication.

Dermatologists prescribe or administer off-label uses of drugs and devices in their practice every day. In some cases, dermatologists may unwittingly make claims about the purpose or effectiveness of unregulated and unapproved health care products, like topical creams, enzymes, or other substances, that may qualify them as drugs or devices and thereby attract the attention of the FDA. The consequences of prescribing unapproved drugs or devices or violating the FDA’s rules for off-label uses can be severe. Dermatologists must, therefore, understand the FDA’s rules and be aware of the other risks associated with unapproved or off-label uses of drugs or devices.

Q: Can I bring a treatment approved in another country back with me and administer it to patients?

A: Dermatologists cannot prescribe or administer unapproved drugs or devices except in very limited circumstances.

The practice of medicine exception applies only to off-label uses of legally marketed drugs and devices. The FDA and courts have long taken the position that the exception does not apply to drugs or devices that have not been approved for any use. While it may seem obvious that physicians should not prescribe or administer unapproved drugs or devices, some physicians may have the misconception that the practice of medicine exception applies to unapproved drugs and devices, or that they can use a drug or device that has not been approved in the United States if it has been approved in another country. This is generally not the case.

Consequently, the FDA regularly issues letters to U.S. physicians, including many dermatologists, who purchase unapproved medications from foreign suppliers, including unapproved botulinum toxin, warning them that doing so is illegal. Thus far, the FDA has taken a relatively gentle approach toward physicians who import unapproved medications or devices, but the potential consequences for doing so can be severe. The FDA has the power to enjoin the use of illegal products or seize them. In addition, the Department of Justice may bring civil or criminal actions against individuals or entities that are disseminating unapproved drugs or devices.

There are some exceptions to the general rule against prescribing or administering unapproved drugs. For instance, physicians can use an unapproved drug or device for purposes of conducting a FDA-approved clinical study under an investigational device exemption (IDE) or an investigational new drug (IND) application.

Physicians may also administer unapproved drugs under the “personal use” exemption. But this exception applies only to individual patients who bring unapproved drugs or devices into the country for their personal use, not to physicians seeking to import unapproved drugs or devices for their professional use. The personal use exception derives from the agency’s enforcement discretion; the FDA emphasizes that while it may exercise this discretion in enforcing the law in individual cases, it is technically illegal to import unapproved drugs into the United States, and that such products may be seized or refused entry into the country at any time.[pagebreak]

Q: Can I market my private-label cosmetic products as regenerative or inflammation-controlling?

A: Dermatologists must be careful not to make claims that convert unregulated health care products into drugs or devices that require FDA approval.

Dermatologists who are administering and/or marketing topical creams, enzymes, or other health care products that have not been approved by the FDA must be very careful not to make claims that these products are intended to affect the structure or any function of the human body, as doing so will render them drugs under the Federal Food, Drug & Cosmetic Act. The same is true for claims that a device is intended for use in the diagnosis of disease or other conditions or in the cure, mitigation, treatment, or prevention of disease, or to affect the structure or any function of the body. In other words, don’t make claims about the purpose or effectiveness of a product that will force the FDA to treat it as a drug or device.

The FDA has not been shy about issuing warning letters when companies have claimed a product regenerates skin cells, rebundles or stimulates collagen production, controls inflammation, boosts the activities of the genes, or stimulates the production of youth hormones and cell regeneration. If a dermatology practice is making similar claims on its website about unapproved health care products, it may attract similar scrutiny from the FDA.

Q: What about off-label prescribing? That’s allowed, isn’t it?

A: Dermatologists can prescribe or administer off-label uses of drugs or devices under the practice of medicine exception.

Congress, the courts, and the FDA all recognize a “practice of medicine” exception to the general prohibition on the marketing of off-label uses. The exception, which is based on the understanding that the states and not the federal government regulate the practice of medicine, allows physicians to use approved drugs and devices in the treatment of their patients without interference from the federal government. It also reflects the understanding that off-label uses often reflect or are dictated by the prevailing standard of care. This means that dermatologists are free to prescribe or administer drugs or devices for off-label uses without worrying about violating FDA regulations. However, there are number of other legal considerations that should be taken into account before doing so.

Dermatologists must be very careful not to promote off-label uses to the general public.

While physicians are free to prescribe or administer off-label treatments to their patients, the FDA does not permit physicians to promote off-label uses of drugs and devices to the general public. That said, a physician advertisement of a medical procedure that involves an off-label use of a drug or device should not be within the FDA’s jurisdiction, as long as the advertisement does not promote the off-label use of the drug or device itself, but instead focuses solely on the medical procedure. For instance, biologic agents have become widely used in the treatment of moderate to severe psoriasis and psoriatic arthritis. If a dermatologist uses a biologic for an off-label procedure, the dermatologist should be able to advertise the procedure, but not the specific type or brand of biologic.

Note that the dermatologist’s advertisement (or website promotion) would still be in the purview of the Federal Trade Commission and state attorneys general to ensure that the content is not false and misleading. To this end, any statements made by the practice must be capable of substantiation through objective medical evidence.[pagebreak]

Whether or not a communication regarding an off-label use is covered by the practice of medicine exception or constitutes an illegal promotion will depend on the particular facts and circumstances. This raises the question whether purely educational information on an off-label use posted on a physician’s website or in a brochure in a physician’s office would constitute an illegal promotion. Any attempt to penalize such communications would likely raise serious First Amendment issues, especially if the physician has no relationship with the manufacturer of the drug or device that is being used off-label, the information disseminated is not false and misleading in any way, and the content has educational value.

Dermatologists can be held responsible for promoting off-label uses on behalf of manufacturers for which they serve as consultants.

As previously noted, manufacturers cannot promote off-label uses except in certain limited circumstances. Where physicians are acting on behalf of drug or device companies in communicating information about off-label uses of specific products, the agency will treat them as agents of the manufacturer subject to the same rules and penalties and not protected by the practice of medicine exception. Whether a physician is acting on behalf of a manufacturer in promoting an off-label use will depend on all the facts and circumstances.

Q: Can manufacturers promote off-label use of their drugs?

A: Manufacturers must follow strict rules about promoting off-label use. Dermatologists should understand these rules before assisting manufacturer dissemination of medical information about off-label uses.

Congress has passed legislation and the FDA has issued regulations that outline the circumstances under which manufacturers may disseminate information on the safety, effectiveness, or benefit of an off-label use to physicians, other health care practitioners, pharmacy benefit managers, health insurance issuers, group health plans, or a federal or state agency. Under these rules, a drug manufacturer can provide peer-reviewed articles on off-label uses to physicians and others covered by the rules if the manufacturer meets certain requirements, such as submitting to the FDA a supplemental new-drug application for the new use, and supplying a copy of the information to the FDA 60 days before providing the information to physicians. The manufacturer can respond to a physician’s unsolicited request for information by supplying peer-reviewed articles or text books.

In 2012, a federal court ruled that a manufacturer’s truthful speech about off-label uses is protected by the First Amendment from FDA regulation. However, a manufacturer’s non-speech actions to promote off-label use are not protected by the First Amendment. In addition, the manufacturer’s speech may be used as evidence of the company’s intent to promote off-label uses.

Presumably, a physician who is paid by a manufacturer to write an article on an off-label use would be subject to the same rules as the company with respect to the dissemination of that article. By contrast, a physician who writes the same article, but has no financial or contractual relationship with the company, should be covered by the practice of medicine exception. In either case, the article itself would likely be protected by the First Amendment as long as it did not contain false and misleading statements about the drug or device.

Q: Can I give lectures about off-label use?

A: Dermatologists can discuss off-label uses at CME events, but disclosure of this fact is recommended.

The FDA has issued guidelines on manufacturer support of CME that relates to the sponsoring company’s products or competing products. The guidelines allow the manufacturer to sponsor such CME as long as the CME activity is independent and nonpromotional, and the company has no influence on the program content or planning.

The Accreditation Council for Continuing Medical Education (ACCME), the primary accrediting body for CME activities in the U.S., has issued Standards for Commercial Support that require CME sponsors to ensure that the content and speakers of seminars funded by industry are independent and not unduly influenced by corporate sponsors. At one point, these standards required presenters at CME events to disclose whether a presentation included discussion of any off-label uses. This disclosure is no longer required under ACCME standards, but it is still recommended, particularly if an educational activity is sponsored by a company whose products will be discussed at the seminar.[pagebreak]

Physicians who speak at CME events about off-label uses of drugs or devices should similarly be protected under the First Amendment for truthful speech, but not for their non-speech actions to assist manufacturers in encouraging physicians to use a drug or device for unapproved indications.

Q: Will prescribing drugs off-label increase my malpractice risk?

A: Dermatologists should ensure that any off-label procedures or treatments they prescribe or administer are consistent with the prevailing standard of care and should obtain informed consent for the use of drugs or devices off-label, where appropriate.

As the FDA has noted in guidance for Institutional Review Boards and clinical investigators, “If physicians use a product for an indication not in the approved labeling, they have the responsibility to be well-informed about the product, to base its use on firm scientific rationale and on sound medical evidence, and to maintain records of the product’s use and effects.” Even then, there can be significant risks in using devices off-label, especially for uses that have not been subject to rigorous testing or long-term application. In such cases, the physician must be careful to obtain informed consent from patients whose treatments involve the off-label use of drugs or devices when such off-label use raises a material risk for the patient. Even if proper consent has been received, using drugs or devices for indications that have not been approved by the FDA and/or well-tested can increase the risk of bad outcomes, the filing of litigation, and findings of malpractice.

Generally, physicians should inform patients of all significant risks, benefits, and alternatives including the fact that use is off-label if such use raises a material risk in the outcome of the procedure. A physician should get written confirmation that the patient understands the information conveyed and needs to be involved in communicating consent information. However, where off-label treatments are routine, clearly constitute the standard of care, and raise no significant risk, there may be no need to mention them in the informed consent process.

Conclusion

Physicians generally may not prescribe or administer unapproved drugs or devices and should be careful not to make claims about unregulated health care products that will lead the FDA to conclude they are administering unapproved drugs or devices. By contrast, physicians have wide discretion to use drugs and devices for off-label indications, except for advertising or promotional activities on behalf of manufacturers. Physicians providing off-label treatments have an obligation to fully understand the risks and benefits of doing so and, where appropriate, to communicate these to their patients. The potential legal risks are significant, and physicians should be especially wary of industry relationships focused on promotion of off-label uses.

 

Reimbursement for off-label or experimental uses

The fact that a medical procedure happens to include an off-label use of a drug or device does not necessarily preclude reimbursement. In general, Medicare pays for drugs that are “safe and effective and otherwise reasonable and necessary.” According to the Medicare Policy Manual, Medicare pays for off-label uses on a case-by-case basis, depending on whether the treatment is “medically accepted, taking into consideration the major drug compendia (or drug reference guides), authoritative medical literature, and/or accepted standards of medical practice.” Physicians should check with their Medicare carrier if they have any doubts about whether Medicare will pay for a service that involves a significant off-label use of drug or device. They should also check their contracts with private payers to ascertain the payer’s policy on payment for off-label uses.

Patients generally cannot be charged for an investigational drug in a clinical trial under an investigational new drug application (IND) without the prior written approval of FDA. Medicare historically did not reimburse for items and services related to clinical trials because of their experimental nature. Since 2000, however, Medicare has reimbursed for routine patient care costs and costs due to medical complications associated with participation in clinical trials. So, if a physician is conducting a clinical trial that involves an unapproved or off-label use of a drug or device, Medicare should reimburse for the routine patient costs and costs of any complications. Here again, physicians would need to check with the relevant private payer to determine its policy on paying for treatment costs associated with a clinical trial that would be reimbursable outside the research context.

 

Key points

  1. Dermatologists cannot prescribe or administer unapproved drugs or devices except in very limited circumstances.
  2. Dermatologists must be careful not to make claims that convert unregulated health care products into drugs or devices that require FDA approval.
  3. Dermatologists can prescribe or administer off-label uses of drugs or devices under the practice of medicine exception.
  4. Dermatologists must be very careful not to promote off-label uses to the general public.
  5. Dermatologists can be held responsible for promoting off-label uses on behalf of manufacturers for which they serve as consultants.
  6. Dermatologists should understand the rules about assisting manufacturer dissemination of medical information on off-label uses.
  7. Dermatologists can discuss off-label uses at CME events, but disclosure of this fact is recommended.
  8. Dermatologists should ensure that any off-label procedures or treatments they prescribe or administer are consistent with the prevailing standard of care and should obtain informed consent for the use of drugs or devices off-label, where appropriate.

 

 

 

Sidebars

Reimbursement for off-label or experimental uses
Key points