Contributed By Shook Hardy & Bacon LLP
The Food and Drug Administration’s (FDA's) Office of Prescription Drug Promotion (OPDP) reviews prescription drug advertising and promotional labelling to ensure the information contained in these promotional materials is not false or misleading. OPDP's mission is “to protect public health by ensuring that prescription drug information is truthful, balanced and accurately communicated.” OPDP has implemented a comprehensive surveillance, enforcement and education programme to address advertising and promotion. OPDP continues to encourage improved communication of labelling and promotional information in order to aid healthcare professionals and consumers. FDA has issued an array of guidance documents to help regulated industry to comply with the regulatory advertising and promotion framework in a variety of communication settings that are outlined in more detail below.
Background on Prescription Drug Promotion Regulatory Framework
The Federal Food, Drug, and Cosmetic Act (FDCA) and Title 21 of the Code of Federal Regulations Part 202 (21 CFR Part 202) primarily govern prescription drug advertising and promotion. Both delineate how pharmaceutical companies can promote prescription drugs to healthcare professionals and consumers. In order to assist the industry and consumers further, FDA has issued many guidance documents over the years, which provide its current thinking on several topics related to prescription drug and medical device promotion.
One of the most crucial requirements of prescription drug promotion in the USA is that companies promote only uses that are 'on label' or consistent with the FDA-approved Prescribing Information (PI). The term 'off label' generally refers to promotion of a product for uses that are inconsistent with the FDA-approved labelling or PI. This 'off label' information may provide additional information regarding the dosing or administration of the drug, other indications for disease treatment or possibly an extension of patient populations that were not part of the original approval. As per FDA regulations, all prescription drug promotion must be consistent with the following: (i) FDA-approved PI, (ii) be truthful and non-misleading, (iii) contain a fair balance of product benefits and risks, and (iv) include material information. 'Material information' refers to anything that may be critical for a patient or healthcare provider to know before or while using a drug that would help to ensure safe and effective use of the product.
Currently companies are required to submit to the FDA every promotional document – including printed, television and website advertisements – at the “time of initial dissemination.” Companies must submit promotional activity for a particular drug product on Form FDA-2253. Furthermore, each ad must contain a variety of elements, such as cited evidence for all claims, a “fair balance” of the benefits and risks of the drug, and any Black Box warnings. OPDP reviews promotional materials submitted at the time of initial dissemination on Form FDA 2253, as well as through routine surveillance and the Bad Ad Program. The Bad Ad is an outreach programme designed to educate healthcare providers about the role they can play in helping the agency to ensure that prescription drug advertising and promotion is truthful and not misleading by providing an e-learning course and case studies. It also allows healthcare providers to report unlawful activity to the agency.
The Evolution of Communication, Social Media and Internet Challenges
Due to the rapid increase of promotion through real-time social media outlets, many pharmaceutical and medical device companies have pondered how to adapt FDA’s current regulatory framework for traditional print advertising in a variety of digital formats. Many internet/social media platforms allow for real-time and continuous communications and interactions (eg, blogs, microblogs, social networks, online communities and live podcasts), while other platforms do not provide a means for interactive content to be posted. In November 2009, FDA held a Part 15 public hearing to gather comments and questions from its stakeholders on how FDA can best provide guidance on the promotion of FDA-regulated medical products using the internet and social media tools.
As a result, FDA released four guidance documents for drug and medical device companies looking to communicate online through social media. In the first of its guidance documents, entitled 'Internet/Social Media Platforms with Character Space Limitations – Presenting Risk and Benefit Information for Prescription Drugs and Medical Devices', FDA provides recommendations for the presentation of risk and benefit information for drugs or devices using the internet and social media sources with character space limitations, such as Twitter.
The second guidance document, entitled 'Internet/Social Media Platforms: Correcting Independent Third-Party Misinformation About Prescription Drugs and Medical Devices', provides insight and recommendations on how manufacturers, packers and distributors of prescription drugs and medical devices should respond to misinformation related to a firm’s own FDA-approved or cleared products when that information is created or disseminated by independent third parties on the internet or through social media. FDA provides suggested approaches a firm may use once it decides to correct the misinformation voluntarily.
The third guidance document, entitled 'Fulfilling Regulatory Requirements for Postmarketing Submissions of Interactive Promotional Media for Prescription Human and Animal Drugs and Biologics', provides FDA’s current thinking regarding how various entities, including third parties, can fulfil regulatory requirements for post-marketing submissions of interactive promotional media (eg, blogs, microblogs, social networking sites, online communities and live podcasts) for their FDA-approved products. The guidance describes what companies must report and how they can submit their materials for review to OPDP. FDA prudently recognised that interactive media often possess “unique technological features and offer novel presentation and content features that set them apart from print.” The guidance states that any material posted to a social media site controlled directly or indirectly by a firm must be submitted for review. FDA further provided examples of influence such as editorial control, preview or review privilege, or collaboration with the poster of the information.
The fourth guidance document, entitled 'Responding to Unsolicited Requests for Off-Label Information About Prescription Drugs and Medical Devices', offers recommendations about how manufacturers and distributors of prescription human and animal drug products and medical devices can respond to unsolicited requests for information about unapproved or uncleared indications or conditions of use (off-label information) related to their FDA-approved or cleared products. This includes requests made directly and privately to firms and requests made in public forums, including through emerging electronic media. This guidance also provides many scenarios that may be encountered and how best to respond with the requested information. FDA is clear that if its recommendations are adhered to that it does not intend to use such responses as evidence of the firm’s intent, that its product may be used for an unapproved or uncleared use.
All the above guidance documents provide recommendations for communications in a variety of non-traditional venues while providing tools to adhere to governing regulations as they pertain to appropriate promotion and advertising of regulated medical products.
Best Practices: Communication of Information Not Contained in a Product’s FDA-Approved Labelling
This past June, FDA also issued two final guidance documents that address how pharmaceutical companies can convey information that is not contained in the FDA-approved labelling to certain audiences, as long as the information communicated is consistent with the FDA-approved label. These guidance documents were developed to resolve longstanding ambiguity in FDA’s approach to regulating communications that concern drug impacts that are not expressly described in the drug’s approved labelling.
The first of the two guidance documents, 'Drug and Device Manufacturer Communications With Payors, Formulary Committees, and Similar Entities – Questions and Answers', provides Agency responses to a series of questions commonly posed by members of the pharmaceutical industry regarding their communications with industry payors, formulary committees, drug information centres and other similar entities (collectively, 'payors'). FDA acknowledges the complexities of communicating with these organisations, which often seek a wide range of information that may overlap with, but also differ from, the information contained in the FDA-approved labelling and the information that FDA reviews in making its approval decisions. This guidance document does not concern direct-to-consumer advertising, or advertising to prescribers who make individual prescribing decisions. It instead provides clear guidance to companies “about open, responsible communication with payors... with the purpose of informing market participants developing contracts that include value-based arrangements how to communicate information about how a drug might impact outcomes that are important to purchasers like a health plan or hospital, but is not an endpoint that is expressly described in the drug’s approved labeling.”
The first of the guidance document’s two parts concerns communication of healthcare economic information (HCEI) regarding approved uses of an approved product to payors. HCEI is any analysis that identifies, measures, or compares the economic consequences, including the costs of the represented health outcomes, of the use of a drug to the use of another drug, to another healthcare intervention, or to no intervention. Such information is often invaluable to payors in making appropriate coverage and reimbursement decisions, and this part provides important recommendations to ensure that HCEI is communicated in a truthful and non-misleading way, and is accompanied by the appropriate background and contextual information to allow payors to make informed decisions.
Where HCEI is consistent with the approved labelling, or where it “relate[s] to the disease or condition, the manifestation of the disease or condition, or symptoms associated with the disease or condition in the patient population for which the drug is indicated in the FDA-approved labeling,” FDA will first consider whether the HCEI contains any material differences (eg, new or increased risks, different dosing or use regimens, different endpoint, more-limited or targeted patient populations) from the approved labelling. If it does not, the pharmaceutical company must clearly and prominently provide – or provide conspicuous access to – appropriate background and contextual information. Where HCEI does materially differ from the approved labelling, pharmaceutical companies should provide “a conspicuous and prominent statement describing any material differences between” the HCEI and the approved labelling.
The second part of this guidance document concerns communications to payors about unapproved drugs or unapproved uses for approved drugs. FDA enumerates seven 'types' of information that it does not intend to enforce against when presented to payors and where the information is unbiased, factual, accurate and non-misleading. Such information should be presented alongside the following: (i) a clear statement that the product or use is not approved and that the safety or effectiveness of the product or use has not been established; (ii) certain information related to the stage of product development; and (iii) where the communication concerns an unapproved use of an approved product, a prominent statement disclosing the indication(s) for which FDA has approved the product and a copy of the most current FDA-required labelling. In addition, where a communication includes a factual presentation of study results, those results should not be selectively presented and should include a description of the material aspects of study design and methodology, and a disclosure of the material limitations related to the study design, methodology and results.
The second guidance document, 'Medical Product Communications That Are Consistent With the FDA-required Labeling – Questions and Answers', concerns the communication of information not contained in a product’s FDA-required labelling, but that may be consistent with that labelling (product communication), including in promotional materials. Product communications that are consistent with the FDA-required labelling are limited to information about the approved uses of a pharmaceutical product. The guidance document presents a series of questions and answers that provide clarity regarding the Agency’s thinking when determining whether the product communications are consistent with the approved labelling.
To do this, the guidance sets forth three factors that the Agency considers when making this determination. Product communications are not consistent with the approved labelling if any of the following is true: (i) the product communication concerns a use or application of the product outside its approved indication(s), patient population, directions for handling/use, or dosing or regimen/administration; (ii) the product communication suggests a use or application of the product that increases the potential for harm to health relative to the information reflected in the approved labelling; and (iii) the approved labelling does not present adequate information (eg, regarding potential or expected risks, effects, unique considerations) to provide the appropriate context that would allow the product to be used safely and effectively as suggested by the product communication.
The guidance document continues to provide illustrative examples and additional detail that will assist manufacturers in determining whether their product communications are, in fact, consistent with the FDA-approved labelling.
These guidance documents are each significant because they further refine for pharmaceutical companies the ways in which they can ensure that all communications – whether to payors, consumers, or other healthcare professionals – are truthful, factual, non-biased and non-misleading.
Possible Consequences of False and Misleading Promotion
OPDP reviews promotional materials submitted at the time of initial dissemination, through routine surveillance as well as through the Bad Ad Program. If OPDP discovers promotional materials to be violative, it may issue regulatory correspondence in the form of an Untitled Letter or a Warning Letter. Both types of enforcement action letters identify the various violations OPDP has found in the promotional materials, which often include the following: false or misleading risk presentation, false or misleading claims about efficacy, and lack of adequate directions for use.
In 2018, OPDP issued seven advertising and promotion enforcement letters, four of which addressed internet-based promotional materials. This is more than half of the enforcement letters issued, signalling that the FDA is addressing inappropriate promotional activities in a variety of settings, including traditional print and internet-based materials, video and oral statements. It is now up to the industry to incorporate the best practices and recommendations of the final guidance documents to avoid FDA enforcement correspondence in the future.