1. General – Medicinal Products

1.1 What laws and codes of practice govern the advertising of medicinal products in your jurisdiction?

Prescription Drugs

In the U.S., prescription drug advertising is primarily governed by the Federal Food, Drug, and Cosmetic Act (FDCA) and U.S. Food and Drug Administration (FDA) regulations and guidance. In certain circumstances, the U.S. Federal Trade Commission (FTC), as well as individual states, retain jurisdiction over aspects of prescription drug advertising as well (e.g., guarantees, pricing claims, limited-time offers, etc.).

The FDCA sets out broad requirements for prescription drug promotion and authorises the FDA to promulgate related regulations. See, e.g., 21 U.S.C. §352(n). The FDA regulations expand on these requirements in the FDCA, adding details to the statutory framework. See 21 C.F.R. §202.1. The FDA has also developed various non-binding draft and final guidance documents relating to a variety of issues in prescription drug advertising, ranging from direct-to-consumer broadcast advertisements to appropriate risk communication in advertising and social media. The FDA has significant discretion in enforcing the FDCA and its implementing regulations to protect the public health of patients prescribed prescription drug products, although the breadth of the FDA's authority with respect to truthful and non-misleading claims that go beyond approved labelling has been called into question by First Amendment case law.

Non-Prescription Drugs

Most non-prescription or "over-the-counter" (OTC) drugs in the U.S. are sold under the terms of regulatory monographs sanctioning a range of specific ingredients, claims and directions for use permitted in such products, without requiring FDA approval. Some are switched from prescription to OTC status, and, more rarely, directly approved for sale OTC. While the FDA regulates the labelling of non-prescription drugs, it does not regulate the advertising; that responsibility largely rests with the FTC, with the exception of certain OTC drugs approved under new drug applications. The FTC has broad authority to address the deceptive or unfair advertising of such OTC drug products. Under 15 U.S.C. §§52–57, the dissemination of false or deceptive advertisements likely to induce the purchase of food, drugs, devices, or cosmetics is unlawful and subject to enforcement by the FTC.

1.2 How is "advertising" defined?

"Advertising" includes any descriptive matter issued or caused to be issued by the manufacturer, packer, or distributor with respect to the drug. See 21 U.S.C. §352(n). Advertising, however, does not include "labelling" as defined in §321(m). Id. While "advertising" and "labelling" are legally distinct concepts under U.S. law, both advertising and promotional labelling are subject to specific FDA regulatory requirements, and both are required to be truthful and not misleading. Advertising is distinct from labelling in that it need not "accompany" the actual product either physically or textually. Nonetheless, various controversies have erupted over whether particular modes of dissemination of information about drug products are properly considered labelling or advertising under the FDCA, such as communications on the Internet.

1.3 What arrangements are companies required to have in place to ensure compliance with the various laws and codes of practice on advertising, such as "sign off" of promotional copy requirements?

While U.S. law does not impose specific requirements on manufacturers to put "sign off" procedures in place, both the FDA and the Department of Health and Human Services Office of Inspector General, which oversees the integrity of government healthcare programmes, have indicated that they expect manufacturers to have an internal review process to ensure that advertising and promotional materials comply with U.S. law and industry Codes of Practice. U.S. government authorities have indicated that they consider an internal, inter-disciplinary sign-off process for promotional materials (in which legal, scientific/medical, compliance and regulatory personnel take part) to be an important part of a manufacturer's compliance programme, and such processes have been required as part of enforcement settlements incorporating Corporate Integrity Agreements. Certain state laws may also arguably require corporate policies of this nature. Generally, once advertising materials are vetted through an internal process, they are then sent to the FDA through the process described in question 1.5.

1.4 Are there any legal or code requirements for companies to have specific standard operating procedures (SOPs) governing advertising activities or to employ personnel with a specific role? If so, what aspects should those SOPs cover and what are the requirements regarding specific personnel?

The industry codes promulgated by the Pharmaceutical Research and Manufacturers of America (PhRMA) and other organisations encourage the development of appropriate processes to maintain compliance, but in large part such SOPs are driven by the range of potential enforcement risks relating to drug promotion. Such SOPs generally govern the review of promotional materials for accuracy, balance, consistency with approved labelling, and compliance with other laws, such as the Anti-Kickback Statute, which would address the fraud and abuse aspects of payments and transfers of value associated with promotion, market research, and other commercial activities.

Under the terms of settlements with the Department of Justice and the states, and industry best practice, most pharmaceutical companies have established internal compliance frameworks, which require review processes and the reporting of violations for further investigation and action. Such SOPs should generally address issues such as (a) who participates in the review (typically commercial, regulatory, medical and legal or compliance representatives), (b) adherence to FDA and other applicable requirements and standards, such as appropriate balance and risk communication, (c) internal escalation processes when consensus cannot be reached on a promotional piece, and (d) submission to the FDA as required under applicable law.

1.5 Must advertising be approved in advance by a regulatory or industry authority before use? If so, what is the procedure for approval? Even if there is no requirement for prior approval in all cases, can the authorities require this in some circumstances?

As a general matter, prescription drug advertisements do not need prior approval by the FDA prior to dissemination. See 21 U.S.C. §352(n). However, upon initial dissemination, all advertisements must be submitted to the FDA Center for Drug Evaluation and Research Office of Prescription Drug Promotion (OPDP) using Form FDA 2253. See 21 C.F.R. §314.81(b)(3)(i). OPDP will also offer comments on advertisements submitted prior to publication, although that can significantly delay use of the materials. See 21 C.F.R. §202.1(j)(4). Manufacturers often submit to review proposed advertisements and promotional labelling intended for use in association with a newly approved drug. In the case of accelerated approval products, which are approved based upon surrogate markers for effectiveness with post-market study requirements, all promotional materials (including advertisements) intended for dissemination within 120 days of approval must be submitted to the FDA during the pre-approval period. See 21 C.F.R. §314.550. Post-approval, promotional materials for such "subpart H" products should be submitted 30 days prior to first use. In certain circumstances – such as under a consent agreement resulting from an injunction – pre-approval of advertising may be required as part of an enforcement action.

1.6 If the authorities consider that an advertisement which has been issued is in breach of the law and/or code of practice, do they have powers to stop the further publication of that advertisement? Can they insist on the issue of a corrective statement? Are there any rights of appeal?

The FDA responds to violations of its advertising regulations through both informal and formal administrative processes. In instances where a manufacturer has voluntarily sought the FDA's comments on a proposed advertisement (or promotional labelling), the FDA may provide a response in the form of suggested guidance through informal communication. In such cases, manufacturers are encouraged but not legally required to accept all of the FDA's comments (though the FDA may take the position that it has placed the manufacturer on notice of a potential violation).

Where the FDA has determined that an advertisement may be or is false or misleading or otherwise violative, it may act by sending the manufacturer either an "untitled" letter or a Warning Letter. Generally, untitled letters set forth the FDA's objections to a particular advertisement and the reasons as to why the Agency believes it may violate applicable laws or regulations. Such letters ask for a response from the manufacturer and results in a dialogue with the FDA to resolve the matter to the Agency's satisfaction.

Warning Letters are generally issued when either a manufacturer has failed to comply with the FDA's requested action in an untitled letter, or where the FDA has determined that a violation has in fact occurred, particularly instances in which the violation is particularly egregious. Warning Letters set forth the particular reasons why the FDA believes the promotional material has violated the applicable laws or regulations. Warning Letters serve as notice for the manufacturer that the FDA may take further enforcement action. Warning Letters also serve as formal notice to an officer of a corporation that a violation of the FDCA has occurred, in the event that subsequent enforcement action is taken against the corporation or an individual officer. Such letters often seek specific corrective action, such as through advertising to correct the violative material or letters to healthcare practitioners.

In the last several years, the FDA has significantly curtailed its use of Warning and untitled letters in this area, focusing on cases involving investigational products, significant safety issues, or clearly false and misleading claims. It is generally believed that this change in enforcement posture is partially a result of changes in First Amendment case law, which, as discussed herein, significantly limits the FDA's ability to deem truthful and non-misleading information as violative.

At the time that an untitled letter or a Warning Letter is issued, the prescription drug to which the violative advertisement refers to can be deemed potentially misbranded. Since distribution of an adulterated or misbranded drug can be a criminal act, manufacturers are required to withdraw and/or correct the violative advertising to the satisfaction of the FDA. Manufacturers may dispute the allegations in the untitled or Warning Letter, or seek to negotiate the scope of required corrective action with the FDA. However, subject to exceptions, the current case law generally does not deem Warning Letters to be final agency action, making it difficult to sue the FDA immediately upon receipt of a Warning Letter. Companies may pursue informal and formal dispute resolution processes, and ultimately could attempt to sue the FDA if they believe the Agency's enforcement theory is arbitrary and capricious or not authorised by law, e.g., unconstitutional under First Amendment speech protections. The FDA has the option of pursuing further enforcement actions at any time, such as seeking an injunction against the company in question, or pursuing a criminal action. Such measures can also be pursued against responsible corporate officials. Third parties may also take action against companies, such as by bringing action under the False Claims Act alleging that a violative promotional activity induced claims for payment for the product under government healthcare programmes.

To read the full article, please click here.

Originally published by ICLG.com.

The content of this article is intended to provide a general guide to the subject matter. Specialist advice should be sought about your specific circumstances.