The pathway of converting a therapeutic orthobiologic concept to a commercially available product is complex and requires input from a range of disciplines and expertise including research and development, management of the regulatory pathway, clinical study design and execution, adherence to a quality system, and eventually, reimbursement. There are now multiple products being used in clinical settings across a variety of musculoskeletal pathologies, with many addressing previously unmet clinical needs. Bringing these complex products to market can be laborious and very expensive, costing as much as several hundred million dollars before the first commercial unit is ever sold. Although the use of allograft tissues (primarily bone, tendons, ligaments, articular cartilage, and dermis) has served as a foundation to service many needs with only modest research and development expenses and regulatory oversight, cell therapy, recombinant growth factor technology, gene therapy, and combination products typically require a decade of development efforts before the first products are FDA approved and available for broad use. Understanding the key activities and hurdles to overcome as inventors and sponsor companies bring a concept through development and onto the commercial market will help clinicians and scientists make informed choices about where to invest their time and resources if they choose to participate in the introduction of new technologies.

The chapters in section 2 highlight the discipline, tenacity, and perseverance required by the product development process from scientific discovery through the FDA and into the clinic. In the field of orthopaedics, the pathways for demonstrating preclinical (as well as clinical) safety and efficacy are very well established and governed by a variety of clearly documented guidelines promulgated by the FDA and the US Code of Federal Regulations. Navigating these development hurdles is resource intensive, and at the very least requires several million dollars for a simple device cleared through the 510(k) pathway (eg, devices for soft-tissue reinforcement or bone void filling), but may require hundreds of millions of dollars for a novel biologic or combination product requiring a biologics license application or a premarket approval (eg, Carticel or Infuse BMP-2).

Even after successfully meeting the FDA’s requirements for market launch, the reimbursement landscape and requirements for getting paid must be considered. Therefore, careful development planning, and the creation of a commercialization strategy early in the process, is essential to determine whether the investment will meet the revenue and profitability objectives of those underwriting the project. With that in mind, ensuring that developers have a robust understanding of the product development process, or that they engage with partners who themselves have a keen understanding of the journey from “bench to bedside” will increase the likelihood of both clinical and commercial success. When meaningful technologic advancements are properly shepherded through the FDA (and other regulatory bodies), it is possible to make both important clinical contributions to the field of orthopaedics and create significant value for those who invest the time and money to succeed.

If an orthobiologic concept is thought to be useful as a product, the first priority is to map out a regulatory plan and product development process together with a cost assessment and revenue projections. This will provide an estimate of a return on investment that ideally becomes positive over time. The cost of bringing a product to market is highly dependent on the regulatory pathway necessary, and this early activity will help define the technologies that can and cannot be used for any given pathology or injury. For example, a product concept for a particular application
that requires a cell-based technology will require a substantial revenue stream to justify the high cost of product development, and if the projected revenue does not support a positive return on investment, then an alternative solution should be explored. The use of financial analysis for each product concept is an important component in determining the technologies appropriate for each envisioned clinical application. As a general rule, the simplest technical solution that meets the least rigorous but meaningful clinical outcome parameters serves as the target product profile rather than overcomplicating matters by attempting to develop a technically sophisticated solution. For example, if a simple scaffold material can support tissue repair adequately, but a genetically modified cell with a novel promoter construct that triggers a downstream signal cascade in the body can achieve a little better outcome, most seasoned product development experts would opt to pursue the simple scaffold.