By Matthew R. Maltese, The Pennsylvania Pediatric Medical Device Consortium, and Daniel Henrich, Archimedic
As a society, we seem to regard the lives of children as more innocent, precious, and worthy of protection than those of adults. This superior valuation of child well-being is not limited to people with children of their own, or those in attendance at pediatric device conferences: in an ongoing MIT study of human perspectives on how autonomous vehicles should behave in the event of an unavoidable collision, respondents regularly indicate the vehicle should be programmed to spare child passengers or pedestrians over adults.[i]
However, the medical device marketplace for children does not reflect these values. There are far fewer pediatric devices than adult devices on the market, meaning one of the most vulnerable patient populations also is one of the most underserved.
In many instances, this reality forces pediatric specialists to find alternative uses for adult devices to treat their patients. One example is a pediatric cardiologist using an adult biliary stent off-label to treat a four-year-old patient with congenital heart disease.[ii] A device designed specifically for that application would, of course, be preferable, but pediatric specialists have to make do, even if the available devices were approved by the FDA to treat a different condition in an adult population.
While devices designed for adults often are repurposed and adapted to treat children out of necessity, this off-label model comes with significant disadvantages. Adult devices often are ill-fitting in pediatric applications and, while physicians follow best practices, consult available literature, and take precautions to protect their patients, the safety and efficacy of devices used off-label has not been established through normal regulatory processes. Innovation or even design iteration of off-label devices is limited, as convincing investors to support a novel device with no regulatory or reimbursement pathway is challenging, to say the least.
Obstacles to Development, Testing, Regulatory Approval, And Reimbursement
The challenges of developing devices specifically for children are primarily market-driven. Objectively, we may believe children deserve access to the best and latest healthcare technologies, but the patient population of children with a particular condition (i.e., the market size) is comparatively small. This is not to say that viable business models do not exist for small medical intervention markets; certainly, compelling value propositions have been developed and come to fruition in orphan drugs.[iii] How to stimulate such an innovation and discovery storm in small medical device markets is an ongoing debate.[iv]
In addition to market challenges, some pediatric device concepts present unique technical challenges that can slow the development, testing, and approval process. A child may depend on a device to perform for a much longer time than an adult patient, and under different — often more active — conditions. A child’s growth also may pose a problem for the device’s function over time, especially an implantable device. Materials may be required that can stretch or be absorbed by the body, but this may not always be possible. Once implanted, a device’s performance may need to be monitored for years before its long-term safety and efficacy can be documented.
These challenges can make it difficult to offset the costs of developing, testing, obtaining regulatory approval for, manufacturing, marketing, and distributing new pediatric devices. Devices for larger adult patient populations typically are more appealing — especially to an institutional investor with a fiduciary duty to its clients — since they offer lower risk and promise higher return due to market size and time-to-market factors.
The good news is that a number of trends are emerging, and initiatives are underway within the industry and at FDA, that focus on enabling pediatric device innovation and smoothing some of the bumps in the road to market.
Pediatric Device Consortia
To help spur innovation in the pediatric device space, the FDA started the Pediatric Device Consortia Grants Program in 2009, with several pediatric device consortia spawned around the United States. In Fiscal Year 2018, the program funded five nonprofit consortia around the U.S. with grants of $6 million (up from $3.6 million in FY2013).
The consortia function in unique ways suited to the approach and capabilities of each member, but also share common characteristics. The first is a common mission to bring new pediatric devices to market to address unmet clinical need. The method to achieve that mission varies by consortium but, in general, each consortium a) oversees disbursement of seed funds to device innovators through an open competition, and b) provides expert advisement and in-kind services to assist innovators along the commercialization pathway.
Such advisement and services include assistance with clinical trials, regulatory strategy, value proposition validation, grant-writing, prototyping, and testing. Each consortium is made up of industry and medical experts, who evaluate the merits of individual proposed projects and assist with decisions and commercialization.
Real-World Evidence (RWE)
As we collect, store, and analyze more data through the healthcare chain, the use of real-world evidence —“information on health care that is derived from multiple sources outside typical clinical research settings, including electronic health records...and data gathered through personal devices and health applications.”[v] — is gaining momentum throughout the device industry, which could pave the way for additional, faster approvals of devices intended for pediatric populations and indications, as well as inform innovators designing new pediatric devices and device trials.
Both the FDA and industry players see the promise of these initiatives. In the past three years, FDA has issued two guidance documents on RWE[vi] and its applications to pediatric devices.[vii] RWE also was the theme of the 2018 Pediatric Device Innovation Symposium, hosted by the Children’s National Sheikh Zayed Institute for Pediatric Surgical Innovation.
Though the use of RWE comes with its own challenges (e.g., conformance to data quality, reliability, and privacy standards), the RWE initiative holds promise for pediatric device and drug developers as we explore more ways to collect and use healthcare data to inform clinical and regulatory practices.
Humanitarian Device Exemption
Similar in many ways to the FDA Orphan Drug program, the Humanitarian Device Exemption (HDE) provides a shorter regulatory pathway for devices intended to treat rare diseases or conditions (8,000 or fewer cases per year in the U.S.). This program exempts devices from certain effectiveness (but not safety) evidence requirements of the FD&C Act.
While there exist limitations to this program, HDE still provides a way to bring devices to market for very small (often pediatric) patient populations that would otherwise be commercially unviable.
Additive Manufacturing / 3D Printing
Additive manufacturing (AM), more commonly known as 3D printing, is changing the way medical devices are produced within and beyond the pediatric sector. Rather than maintaining an inventory of devices in every possible permutation of size and shape, manufacturers and hospitals can invest in on-demand manufacturing.[viii]
Using 3D printers, devices can be produced in a growing number of materials, at comparatively low cost, and in very small quantities. Devices even can be customized to a particular patient (i.e., “patient-matched devices”), which can be especially helpful in applications like prostheses, where needs vary greatly between patients and change rapidly as a child grows.
According to FDA guidance issued in late 2017, “AM has the advantage of facilitating the creation of anatomically-matched devices,” as well as facilitating the creation of device structures “that would not be easily possible using traditional (non-additive) manufacturing approaches.”
That said, the newness of AM-produced devices, and their lack of clinical history, introduce certain unknowns into the highly controlled process of device manufacturing. Specifically, the FDA’s 2017 guidance notes that the “innovative potential of AM may introduce variability into the manufacturing process that would not be present when using other manufacturing techniques.”[ix]
Though advances are being made, many of the initiatives above are in their infancies, with much more progress needed before we can declare them successful. Solving the problems of pediatric device commercialization will take more great ideas and initiatives than those discussed above. We need clinicians, engineers, entrepreneurs, impact investors, regulators, and legislators working in concert to build on our progress in this area. All of these players, and others, must come together to develop creative solutions to overcome the market challenges that derail so many promising pediatric device projects in today’s environment.
This article is based on a Archimedic podcast interview between Matthew Maltese and Daniel Henrich about pediatric device innovation; you can listen to the conversation here.
About the Authors
Matthew R. Maltese is the Founding Executive Director of the Pennsylvania Pediatric Medical Device Consortium, where he works to support early stage pediatric device teams as they progress towards commercialization. He is also Chief Innovation Officer at X-Biomedical, a medtech startup.
Daniel Henrich is Director of Marketing at Archimedic (formerly Smithwise), where he works to educate industry members about medical product development and how Archimedic can help their organizations advance healthcare through breakthrough medical technologies.
About The Pennsylvania Pediatric Medical Device Consortium
The Pennsylvania (formerly Philadelphia) Pediatric Medical Device Consortium connects Children’s Hospital of Philadelphia (CHOP) with the McGowan Institute for Regenerative Medicine and sciVelo, both based at the University of Pittsburgh. This new partnership comes on the heels of a five-year, $5 million grant renewal from the Consortium’s sponsor, the U.S. Food and Drug Administration. The mission of the PPDC is to support the development and commercialization of promising medical devices that address unmet clinical needs in children.