CELLULAR AND GENE THERAPIES

To affirm that the pharmacy workforce serve key roles in the use of cellular and gene therapies (CGTs), spanning supply chain management, operational oversight, and clinical consultation on individual patients; further,

To recognize that CGTs are managed in the medication-use process; further,

To assert that health-system decisions on the selection, use, and management of CGTs are made through the formulary system; further,

To advocate for payment models that facilitate patient access, coverage, and reimbursement for CGTs with consideration of total cost of care; further, 

To advocate for manufacturer processes that decrease the burden and resources required for hospitals and health systems to use CGTs.

Rationale

Currently, cellular and gene therapies (CGTs) are defined as "Advanced Therapy Medicinal Products", comprising a large group of cellular types that are either alone or in combination with gene and tissue engineering technology. The U.S. Food and Drug Administration (FDA) recognizes cellular therapy products as cellular immunotherapies, cancer vaccines, and other types of both autologous and allogeneic cells for certain therapeutic indications, including hematopoietic stem cells and adult and embryonic stem cells. The FDA regulates CGTs as biological products, meaning they are considered therapeutics subject to standard drug regulations. The FDA recognizes human gene therapy seeks to modify or manipulate the expression of a gene or to alter the biological properties of living cells for therapeutic use. Together, CGTs are a rapidly growing and important area of medicine. The 2023 AJHP article Role of Pharmacy in Cellular-Based Therapy cites the need for pharmacists to take a leadership role in managing CGTs and delineates three major areas for pharmacy leadership: biologic drug management, multidisciplinary team coordination, and supportive care management. Additionally, the pharmacist, working collaboratively with the interdisciplinary team, should take the lead in ensuring successful use of CGTs (e.g., patient navigation, care coordination lead, proactive review, and assessment for eligibility and reimbursement, measuring and monitoring outcomes). Like other therapeutics, CGT agents should be managed as a part of the formulary system. As described in more detail in the ASHP Guidelines on the Pharmacy and Therapeutics Committee and the Formulary System, a fundamental characteristic of the formulary system is that all decisions are made based on evidence-based clinical, ethical, legal, social, logistical, philosophical, quality-of-life, safety, and economic factors that result in optimal patient care; include the active and direct involvement of physicians, pharmacists, and other appropriate healthcare professionals, as well representatives with expertise in finance, law, and informatics; and are not based solely on economic factors. 

However, as reported in the ASHP/ASHP Foundation Pharmacy Forecast 2024, the ultra-high expense of these therapies, coupled with uncertain reimbursement, warrants careful financial, service-line, and external partnership analyses. Pharmacy leadership, service-line stakeholders, and the pharmacy and therapeutics committee should collaborate with health-system finance experts to gauge budget impact and measure financial risk associated with the provision of CGTs. Pharmacy should be integral in the development of procedures regarding storage, prescribing, dosing, preparation, labeling, dispensing, transport, safe and compliant administration, clinical decision support tools, and disposal when working with CGTs. To ensure the accuracy of the dose, product, and labeling, pharmacists should have the ability to verify the product when it’s prepared in the pharmacy and should be involved when order sets or labeling procedures are developed.  Well-known challenges are presented by the use of these agents in structuring clinical decision support tools. These agents are often measured in volumetric dosing (e.g., vector genomes per kilogram), and their documentation often requires use of exponents. Therefore, ASHP recognizes, as part of the medication-use process, the need for innovation in electronic health records and pharmacy workflow systems so that these doses can be displayed accurately while avoiding the use of free text in the electronic health record, which may lead to dosing and entry errors. Safety checks, including robust double check systems, should be in place to avoid errors due to compounding and order entry. Finally, advocacy for patient access to, full coverage of, and reimbursement for CGTs is necessary to develop new capabilities and enable pharmacy services to adapt to these new ultra-high-cost therapeutic innovations. 

Public and private payers lack coverage policies and restrictions for CGTs. Many payers use traditional pricing models, such as fee-for-service or utilization management tools, to manage CGT but these models are not suitable for ultra-high-cost therapies. Some hospitals may lack economies of scale to support CGTs and may choose to opt-out of providing them to patients due to insufficient reimbursement. For instance, many hospitals consistently lose revenue on CAR T-cell therapy due to the high readmission rates within 72 hours that are then tied to the diagnostic related groups. CGTs are time intensive therapies, requiring hospitals to take on financial risk. Hospitals should be paid at cost plus and reimbursement, which should not be dependent on readmission factors due to CGT drug-related events. Several payers plan to leverage reinsurance (e.g., annuity payments) as well as increase their use of value- and outcomes-based contracting. However, legal and regulatory barriers currently prevent or limit the use of innovative, value-based payment models. One value-based agreement under consideration ties reimbursement to value and durability, such as CGT developers reimbursing payers when therapy does not provide sufficient benefit. This approach has the potential to incentivize manufacturers to develop effective therapies, while also ensuring patients receive the best possible treatment. Reimbursement and pricing challenges faced by CGT are complex and require innovative solutions. Value-based arrangements and reinsurance are potential models that could help address these challenges.