Combination products may provide new opportunities over single-entity drugs and biologics for various stakeholders in the healthcare system. Patients may realize ease of use or improved adherence. Clinicians may prefer the novel delivery method and convenience. Sponsors may look to develop combination products due to enhanced efficacy and the benefits conferred to patients and clinicians. Sponsors may also benefit from the broadened opportunities for formulation strategies and lifecycle management. These opportunities are accompanied, however, by new regulatory, coverage, coding, pricing, and reimbursement considerations.

As combination products have become increasingly prevalent, the term has grown to encompass a wide range of product types. Even defining the term “combination product” can become challenging depending on the audience present. Clinically, a combination product consists of any two or more products within the same treatment regimen. According to the Food and Drug Administration (FDA), “a combination product is a product comprised of two or more different types of medical products (i.e., a combination of a drug, device, and/or biological product with one another).” The FDA defines nine categories of combination products and further distinguishes them based on several factors, such as how they are packaged. As a result, drug and device manufacturers have a multitude of options for the development of a single combination product, and each option will have implications for commercialization.

Combination Product Lifecycle Management

Due to the variability in the types of combination products that can be launched, manufacturers need to understand the upstream and downstream effects to ensure key decision points are identified early. Stakeholders should consider impacts across several periods of the product lifecycle.

• Coverage and Market Dynamics: The type of combination product that is developed, filed at the FDA, and launched has a significant and nuanced influence on market success.
• Reimbursement: Decisions regarding an FDA application and regulatory strategy for the combination product not only affect downstream coding but also provider or pharmacy reimbursement by payers, particularly if multiple formulations of a product are available on the market.
• Coding and Pricing: The type of FDA application filed may be a defining factor in the eligibility for unique coding and pricing for the product.
• FDA Filing: The design of clinical trials and evidence generation strategy and existing on-market formulations of an active ingredient will determine the pathways available for approval or licensure of a combination product (and, as a result, the regulations that apply to the combination product).
• Clinical Development: The targeted type of combination product may influence the design of clinical trials and the type of data that will be required by the FDA.

As outlined above, the factors influencing market differentiation demonstrate the need for sponsors to consider downstream commercialization factors early during clinical development.

Policy Impacts on Combination Product Lifecycle Decisions

Over the past decade, interest in combination products may have increased due to the clinical effectiveness and differentiation they offer relative to single-agent drugs and devices. Future investment in the space may be bolstered by the recent policies of the Inflation Reduction Act (IRA), particularly the Medicare drug price negotiation. The risk for Medicare negotiation later in a product’s lifecycle will change manufacturers’ approach to early clinical and FDA decisions. The development of combination products may simultaneously offer both improved patient access and a delay of negotiation pressures, though the extent of the IRA reprieve will be determined by further rulemaking and monitoring of the Centers for Medicare and Medicaid Services’ actions.

How Avalere Can Help

Avalere experts in regulatory strategy, drug pricing, market access, and the IRA can help you evaluate lifecycle management decisions, including understanding how policy changes impact your organization and your industry. To better prepare for and shape the changing healthcare landscape, connect with us.