Working with the Campbell Alliance Group, Inc., the Center’s newly published report, Assessing the Impact of Risk Evaluation and Mitigation Strategies (REMS) Requirements on the Pharmaceutical Supply Chain, documents the impact of the REMS mandate on manufacturers (brand, generic, biologic and small-molecule drugs); distributors (traditional wholesale, specialty and self-distributing specialty pharmacy); and providers (physicians, nurses, patient advocates and retail and specialty pharmacists). Using interviews and secondary data, this timely research presents opportunities, challenges and recommendations for process improvement and, for the first time, offers insights into the economic impact of REMS.

Background
REMS originates with the 2007 FDA Amendments Act, which authorized FDA to require REMS from manufacturers to ensure that the benefits of a drug or biological product outweigh its risks.

These strategies reflect FDA-approved manufacturer mitigation objectives and can be described as simple or complex programs that are broken down into four components. “Simple” REMS employ one or more of the first two components: medication guides for patients and communications plans to educate healthcare professionals. “Complex” REMS add elements to assure safe use (ETASU)—such as training, certification and registries documenting compliance; and systems to implement the ETASU. All strategies require assessment tactics and timetables to measure the strategies’ mitigation effectiveness (Fig. 1). More than 175 drugs currently have REMS; the most recent requirement being a class-wide mandate for long-acting and extended-release opioid products.

 

Industry guideposts
Assessing the Impact reviews the four stages of a REMS program (planning, implementation, monitoring and assessment) to illustrate how key supply chain stakeholders are affected. Even simple REMS were noted to present supply chain issues that are time-consuming and carry the potential to adversely affect patients. For example, it was noted that the manner in which a medication guide is formatted, distributed and understood can help or hinder its use and therefore its viability as a mitigation tool.

The study offers lessons learned noting that distributors, dispensers and providers all wish to be involved in the design and implementation of REMS programs. This appeal underscores their desire to provide input into the program, obtain sufficient time to develop internal training to ensure smooth program execution and time to test each system prior to product launch. Interviews with manufacturers revealed a growing willingness to work with downstream partners while advancing with the design of new REMS programs.

Stakeholder perspectives
To understand the issues associated with as well as the costs and benefits of REMS from a supply chain perspective, each interview participant was asked to prioritize their concerns.
Sample groups of manufacturers, distributors and healthcare providers provided comments on concerns or priorities in administering REMS programs. All study participants expressed reservations about delays that ultimately may hinder patient access to drugs. Distributors, who have a concern for meeting manufacturer expectations, would prefer to be more involved in program planning. Providers have a concern for unreimbursed costs, and express a desire for standardization of processes, especially in cases where dozens of different programs—all with different requirements—impact the prescribing and dispensing processes.

The study’s economic analysis indicates REMS requirements are costly to the supply chain and underscore the need for additional research into REMS program costs, including those that are hidden, unforeseen and not reimbursable through current business practices and government benefit programs. Assessing the Impact includes separate sections reviewing tasks and associated of REMS for manufacturers, distributors and healthcare providers. These data were based on interviews and documentation from:

Manufacturer:
• Medical Affairs
• Brand management
• Trade relations
• Safety
• Regulatory
Distributors:
• Specialty pharmacy/distributor
• Hub services
• Wholesaler/distributor (serving retail)
Healthcare providers:
• Physician
• Nurse
• Pharmacist

For manufacturers, costs are divided between setup and monthly maintenance. Each line item ranges from a low of $5K-250K, to a high of $100K-500K. Development times range from 20 to 120 days, depending on the task. For distributors, line items range from “minimal” to $5K-$1M (indicative of the wide range of data reporting that can be required). Healthcare provider economics are evaluated on the basis of time estimates to complete various tasks; for example, physicians’ patient counseling is 10-15 minutes (per patient), while physician certification can require an hour. Fuller details are available in the report.

Case studies
Assessing the Impact presents case studies to underscore the complexity of REMS programs that were developed for three commercial products: generic isotretinoin (the iPLEDGE program); Amgen’s Nplate (romaplostim) (the NEXUS program); and GSK’s Promacta (eltrobopag) (the CARES program). These cases, selected to provide insight to both the specialty and retail segment of the pharmaceutical supply chain, reveal lessons learned and the importance of communication among supply chain participants. Each case details the flow of product, money and information, as well as entities requiring registration and discusses program management.

Finally, the research provides recommendations on future enhancements for REMS, as well as other insights that are helpful to anyone seeking to understand the potential impact of REMS on the pharmaceutical supply chain. Key findings highlight the need for supply chain collaboration, the need to build on the experiences past REMS and the need for uniformity in programs, operating procedures, data management and communications. PC

BOX:
The report Assessing the Impact of Risk Evaluation and Mitigation Strategies (REMS) Requirements on the Pharmaceutical Supply Chain is available for purchase. For more information, contact Tonya Martin of the Center for Healthcare Supply Chain Research at tmartin@hdmanet.org. 



ABOUT THE AUTHOR
Karen Ribler is Executive Vice President & COO for the Center for Healthcare Supply Chain Research (Alexandria, VA; 703 885 0256). Previously, she was president of KJR Consulting, and from 1990 to 1998, executive VP and COO of the National Food Brokers Assn. Educational Foundation. Ribler holds graduate degrees from Northwestern University.

The Center for Healthcare Supply Chain Research is a 501(c)(3) non-profit charitable organization that serves as the knowledge partner of the Healthcare Distribution Management Association (HDMA). The Center’s mission is twofold: to conduct research and disseminate information that will enhance the knowledge base, efficiency and effectiveness of the total healthcare supply chain; and to provide thought leadership to further enhance the safety and security of the healthcare supply chain through future-focused study and programming.