Risk management in the drug industry changed forever in September 2007 when the Food and Drug Administration Amendments Act (FDAAA) was signed into law. The FDAAA granted the FDA explicit authority to require a Risk Evaluation Mitigation Strategy (REMS) to order safety labeling changes, to require post-marketing studies, and to impose civil monetary penalties for violations of REMS provisions. The REMS requirement was developed from earlier RiskMAP guidelines to ensure that the benefits of a product outweigh its risks in actual use. REMS tools can include medication guides, restrictions on distribution and comprehensive communication plans.

“The concept of risk management for pharmaceuticals changed the dynamic of drug development and approval,” says nationally recognized regulatory expert Wayne Pines, CCC Advisory Board Chair and former FDA associate commissioner. “An effective REMS program not only provides greater assurance to the FDA that a drug will be used safely, it also enables the FDA to approve drugs that might not have been approved before, given concern they would not be used safely. Getting these drugs approved is a great challenge, but also a great opportunity for industry.”

This new approach to risk management reflects a shift in roles for both the FDA and drug companies which historically focused on product safety based on doctors’ using drugs according to the approved labeling. Under REMS, safety concerns are addressed in a much more comprehensive way.

REMS regulations require that companies conduct risk assessments during the clinical testing phase and include those risk data in the new drug application, along with a REMS program if one is needed.

The REMS Compliance Challenge

Part of what makes REMS compliance so challenging is the comprehensive and ongoing nature of REMS programs. The FDAAA authorized the FDA to declare an approved product misbranded (and thus ineligible for marketing) if the company fails to follow an approved REMS, including complying with the required periodic assessments. Additionally, the FDA may require post-marketing studies for some products under REMS or can delay product approval if it deems the submitted REMS to be insufficient.

Sometimes a REMS program may add significant complexity to marketing high-risk products when restrictions limit the kinds of healthcare professionals who can a prescribe a drug, the training and registration of these individuals, conditions as to the specific settings in which the drug can be administered, and the continuous tracking of all these components for compliance.

However, REMS should be viewed by companies “not as a burden, but as an opportunity to position a drug for maximum best use,” states Pines. “Industry must view REMS positively and not just as something that is legally mandated. Ultimately, REMS represent an opportunity to proactively manage the communication of critical information.”

Communication Professionals Must be Proactive

Clearly, the adoption of a REMS increases a company’s responsibility to communicate risk information accurately, effectively and in a proactive and timely manner. Furthermore, the REMS requirement needs its own communication plan so that the medical and pharmacy communities and patients will understand why special provisions are required for a particular product. This prevents the “black eye syndrome” in which key stakeholders interpret a REMS as a brand deficit. Marketing communication professionals should be prepared to address tough questions regarding a REMS once it is announced. If a REMS is required after a product has been approved and is already on the market, communication professionals need to be prepared to address questions from the media and from advocacy groups, in addition to physicians and patients.

A key condition of the REMS provision within the FDAAA is that an assessment of the implemented REMS program must be submitted to the FDA at 18 months, three years, and again at seven years. For the proactive marketing professional, these mandated milestones can serve as ideal opportunities to reinforce a company’s commitment to providing the safest drugs available and to managing risk across the entire lifetime of a drug.

A Collaborative Effort

REMS is not just one function’s responsibility. Global executives must actively communicate across cross-functional teams—from R&D and clinical to legal, regulatory and compliance—to manage risk throughout all drug development phases. This includes marketing communication teams who can help highlight the necessity for and implementation of REMS to diverse stakeholders, for example:

  • All company employees involved in drug marketing, especially the field sales force that communicates directly with physicians, must be educated on the details and value of a REMS program for each product. This ensures that both its implementation and its follow-up execution are seamless.
  • Physicians and patients, including those from diverse cultures, must comprehend the required REMS and the associated messages.
  • Investor relations professionals must also carefully craft communications targeted to potentially fearful investors.

REMS and Other Safety Strategies are Growing

Risk management must be on everyone’s radar these days, given the ever more complicated regulatory environment, and REMS is only one of the FDA’s efforts. The agency has publicly acknowledged that risk communication is a key component in the effective management of medical product risks. Pharmaceutical companies operating within the jurisdiction of the FDA have great responsibility to manage risk at every stage of their business, from early discovery of a drug to post-marketing communications.

Sidebar: Answers to Commonly Asked REMS Questions

Will a REMS add time to the FDA approval process, or can a well-designed REMS streamline the approval process?
The approval process should not be unduly delayed if companies do their due diligence, including assessing REMS best practices. This can be accomplished by reviewing cases where drugs have implemented risk management or risk minimization programs (e.g., Lotronex, Xyrem), as well as drugs currently with REMS (e.g., Entereg and Xenazine). Companies need to ensure that the REMS is compatible with established distribution, procurement and dispensing systems. And of course, a company must have an open and ongoing dialogue with the FDA.

Will or do post-approval marketing tactics change with REMS?
Companies with REMS should not have to change marketing goals if they have been committed to fairly balanced promotion and comprehensive education for their promoted drugs from the outset of the communications continuum.

What are the basic “best practice” steps in developing a REMS?

1. Start Early: Begin discussing risks in the pre-clinical phase.
2. Think Long-term: Never forget that measurement of the success/failures of a REMS program must be submitted to the FDA no later than at 18 months, at three years, and then again at seven years.
3. Involve Communication Experts: To date, communications pros have not been fully integrated into REMS planning teams. This is inefficient and unproductive because REMS are essentially communications programs at the very highest level. Risk information must be understood and result in safer use outcomes. Companies should invite corporate communications, marketing communications and other messaging veterans to the strategic planning table when REMS are being designed.

How does a REMS affect different sectors of the industry (marketing, clinical, sales, drug patent, drug development)?
Internal stakeholders need to work hand-in-hand to effectively define and act on critical points for risk management. That’s why the biggest change and challenge for these diverse sectors is learning to collaborate early and often.

  • Ilyssa Levins

    Ilyssa Levins is President and Founder of Center for Communication Compliance (CCC). Ilyssa helps manufacturers and their promotional agencies save time, money and manage risk, when promoting drugs and devices. She combines her regulatory compliance, marketing communications, and change management expertise to help clients achieve their goals.


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