Editor’s Note: The promotional review process requires a critical balance between ensuring materials achieve business goals and complying with regulatory constraints. There often can be friction on the promotional review committee (PRC) between the marketing team and participants representing medical, legal and regulatory issues. But in the end, everyone has the same core objective—optimizing commercial success while keeping the company safe.
How can you reduce conflict on the PRC and work together efficiently across different functions to achieve a common goal? What are the Food and Drug Administration (FDA) regulations you need to keep top of mind when evaluating messaging—and how does the Federal Trade Commission (FTC) come into play for life sciences advertising? What are best practices for “fighting fair” on the PRC—and reaching the optimal result? Manatt provided the answers at a recent webinar, presented through PharmaVOICE. In part 1 of our article summarizing the webinar, below, we discuss PRC procedures, the legal/regulatory framework, the players and their roles, PRC best practices, and recent warning and untitled letters. Watch for part 2 of our summary in the December “Health Update,” providing an overview of FTC law; the interaction between the FTC, FDA and state attorneys general; and a review of pertinent cases.
Promotional Review Standard Operating Procedures (SOPs)
It is critical for every PRC to have SOPs to follow that clearly define the roles and responsibilities of each member, as well as explain the escalation process, if the PRC fails to reach agreement. The SOPs also should identify standing and adjunct members, as well as who owns the PRC from an administrative standpoint (typically the regulatory representative who sends out meeting information and reminders). In addition, the SOPs should set timelines for sending documents prior to the next meeting, specify what will be stored in the electronic or paper review systems, and define the process for the regulatory team to submit documents to the Office of Prescription Drug Policy (OPDP).
Legal and Regulatory Considerations for PRCs
PRCs play a crucial role in reviewing materials to ensure legal, regulatory and medical compliance prior to external or internal use. The most important statutes for the PRC are the Food, Drug, and Cosmetic Act (FDCA) and Title 21 of the Code of Federal Regulations (Title 21), which primarily govern prescription drug advertising promotions.
The FDA approves drugs for specific indications and prohibits manufacturers from promoting a drug “off label” (for any unauthorized use). In addition to prohibiting off-label marketing, the FDCA requires that all advertising and promotional materials be consistent with approved prescribing information, be truthful and not misleading, include all material information, and present a fair balance of information about the drug’s benefits and risks. Failure to adhere to the provisions of the FDCA and Title 21 may cause a drug to be deemed “misbranded.” Violations also can be punishable by both civil and criminal penalties.
PRCs also need to consider the Anti-Kickback Statute (AKS), which makes it illegal to offer or pay, directly or indirectly, “remuneration” (defined as anything of value) to a healthcare professional or customer to induce him or her to prescribe, order or recommend products or to reward past purchases or use of products reimbursed, in whole or in part, by a federal healthcare program. Many types of materials could potentially implicate the AKS, such as patient assistance programs and physician speaker programs, so it is important to be cautious and heed regulatory counsel. It also is important to stay on top of new and evolving developments, such as recent First Amendment cases asserting the ability to discuss topics outside the label due to free speech and scientific exchange considerations.
In addition, PRCs should be following the two FDA guidance documents that were released in June 2018:
- Medical Product Communications That Are Consistent with the FDA-Required Labeling—Questions and Answers (referred to as the CFL Guidance) and
- Drug and Device Manufacturer Communications with Payors, Formulary Committees and Similar Entities—Questions and Answers.
Again, failure to review materials properly and follow relevant regulations and guidance can lead to significant consequences, including the need for a corporate integrity agreement or a warning letter.
Typical PRC Players and Their Roles and Responsibilities
The differing roles on the PRC can often lead to conflict. Following are the typical players on the PRC, along with their key responsibilities:
- Marketing. The marketing role focuses on creating optimal messaging and promotional and sales materials to maximize sales and prescriptions. Marketing team members tend to be creative, assertive and think outside the box.
- Medical. The medical reviewer is charged with reviewing materials and references to ensure that the data and claims accurately reflect label and source materials from the medical/clinical perspective. Medical reviewers tend to be conservative, scientifically and clinically oriented, and focused on data.
- Regulatory. The regulatory reviewer reviews materials to ensure the language accurately ties to the label and that the materials are fairly balanced in presenting both benefit and safety information. He or she also is responsible for submitting materials to the FDA/OPDP. Regulatory reviewers tend to be detail oriented, risk averse and focused on following the rules.
- Legal. The legal reviewer also reviews materials to ensure they are on label, so there is some overlap with the regulatory reviewer role. In addition, the legal reviewer identifies issues that could raise legal concerns, such as potential problems with false claims or the AKS. Legal reviewers tend to be assertive and detail oriented and, depending on their experience, may also be conservative and risk averse.
A Deep Dive into the Legal, Medical and Regulatory Reviewer Roles
We are going to take a deeper dive into the legal, medical and regulatory reviewer roles to ensure the distinctions are clear. Understanding the roles of each PRC team member limits conflict and fosters appreciation for the value that every participant brings to the review process.
Legal reviewers must confirm that the materials are in compliance with all relevant federal, state and local laws, as well as with company policies. They also must ensure that there is a fair balance between benefit and risk information, that the information presented is not false or misleading, and that the images or graphics are appropriate for the target population. In addition, they must check the appropriateness of any comparative claims under applicable regulations and legal principles. Comparative claims can be a problematic area. It is critical that any comparative claims can be backed up by solid data from actual head-to-head studies. Other responsibilities include ensuring that:
- Information is presented in the appropriate context, based on the target audience (such as internal, professional or patient), the content, and the medium being used for dissemination (such as print, TV or social media).
- Trademarks, copyright and other intellectual property are used appropriately.
- Non-FDA legal issues are considered (such as fraud and abuse laws, the AKS or reimbursement regulations).
Ultimately, the legal reviewer is responsible for limiting the company’s exposure to liability.
Medical reviewers must confirm that any information presented is medically and scientifically accurate, clinically and statistically relevant, and presented in the appropriate context and level of detail. If marketing pulls portions of information from the label, the medical reviewer must ensure that it is clear from a medical standpoint, consistent with the label and an accurate reflection of study results.
Medical reviewers also must ensure that any references used to support claims are appropriate (i.e., reflect adequate and well-controlled studies) and applicable (i.e., are based on clinical studies and not extrapolations from nonclinical data). In addition, they must check that any statements around clinical trial data match the actual results. Finally, they must confirm that images or graphics are appropriate for the target population, are on label and are medically accurate.
Regulatory reviewers must ensure that all materials comply with FDA laws, regulations and published guidance. It is critical that they are fully up to date on all regulatory requirements, from font size to fair balance—and that they are aware of any recent warning and untitled letters that may give additional guidance. In addition, they confirm that the balance between risk and benefit information is distributed throughout the materials—and that both safety and efficacy information are given appropriate prominence.
In addition, they check that the information presented is not false or misleading. They also assess images and graphics to be sure they are appropriate for the target populations and are on label in terms of conveying information about dosing, treatment and outcomes.
Regulatory reviewers analyze comparative claims to ensure they are supported by substantial evidence. They also are responsible for making sure that PRC members are aware of any label changes and relevant regulatory actions. Finally, they are responsible for guiding the PRC in making the strategic decision about whether to submit certain materials for preapproval and comments to the OPDP or to wait and submit materials in conjunction with their use in the field.
PRC Best Practices: Managing Conflicts and Playing Fair
To be effective, PRC members must remember that they are on the same team and share the same goal—to create materials that effectively promote the product in a manner that is compliant with applicable regulations and company policies. It is essential that all PRC members are focused on achieving the balance between meeting business objectives and keeping the company safe.
It is critical for reviewers to understand and respect marketing’s role of being creative and coming up with ideas that optimize the product’s attributes. Marketing has the difficult job of differentiating the product from competitors in the marketplace. It is equally critical, however, for marketing to recognize and respect the roles of the legal, medical and regulatory reviewers to keep the company safe by ensuring that all marketing materials are on label, fairly balanced and medically and scientifically accurate.
When issues do arise, how can everyone work together to mitigate conflicts? It helps to start by identifying the overarching goal of the campaign and the specific piece in question. A shared understanding of goals can help members see things from each other’s perspectives and recognize the value that each brings to the discussion.
In addition, rather than saying a blanket “no,” try to come up with alternative suggestions that get the group to a “yes”—other options for achieving the agreed-upon goals while still being compliant. Seek to find common ground first—to say “we agree on all these things but this one specific aspect may need to be changed.” Through any discussion, it is important to maintain a professional tone, be respectful and avoid taking things personally.
Other approaches that help PRC members work together efficiently from different perspectives include:
- Working together up front on a core claims review to limit conflict and discussion at meetings
- Reaching agreement on alternative language for certain topics, as similar issues present themselves across different materials
- Providing comments and revisions prior to live PRC meetings, so reviewers are aware of each other’s feedback
- Letting marketing prioritize issues to make live meetings more productive
- Establishing trust and friendship by connecting on a personal level through social events or other gatherings outside the PRC context
- Meeting early and often, recognizing that stress levels ramp up as approval and launch dates get near
- Managing stress by being prepared—and having issues and materials vetted ahead of deadline
Even when PRCs make every effort to work together, they sometimes hit an impasse. If that happens, it can be most effective to elevate the issue to a senior decision maker to make the final call. This approach can limit the conflict by allowing a neutral party to decide. When escalating a conflict, it is important that the issue not be presented as asking the decision maker to “pick a side.” Information on the issue should be shared objectively, identifying both the opportunities and the risks.
Overcoming Challenges of Co-Promotions
Co-promotions can be particularly challenging, as they involve working with PRCs across different companies that may have different levels of risk tolerance. It can be very helpful to get to know co-promotion counterparts in offline discussions before the first PRC meeting, so each party can understand any differences between the organizations. It also can help the process run more smoothly to address ground rules and set expectations early, as well as to meet in person and establish relationships prior to heavy activity. Creating a level of trust, finding common ground and setting shared goals all help to ensure a more effective and productive co-promotion process.
When dealing with a co-promotion partner, it also is important to be sure the internal PRC team is fully aligned—and to pick any battles with the partner carefully. If there is a conflict that can’t be avoided, make sure to respect counterparts on the partner’s PRC and try to understand their viewpoints. If agreement can’t be reached, escalate the issue to a senior business executive to facilitate the decision-making process.
Recent Warning and Untitled Letters
Recent warning and untitled letters can provide valuable insight to help guide PRC decisions. Examples include:
- Direct-to-consumer (DTC) print and banner ads made misleading claims about the brand’s risks and efficacy. The print ad provided evidence that the brand was intended for a new use for which it was not approved. These actions led to a warning letter and claim of misbranding.
- A webpage focused only on the efficacy of products without fair balance, leading to a warning letter.
- A Facebook post sponsored by the manufacturer of a boxed warning drug included only efficacy information with no representation of safety risks. The implication that there were no risks led to a warning letter and claim of misbranding.
- A DTC video of an interview with a company spokesperson aired on TV and the web—and failed to include information on the product’s risks. An untitled letter deemed the video “false and misleading” and led to a claim of misbranding.