A new guidance document published by the US Food and Drug Administration's (FDA) Center for Devices and Radiological Health (CDRH) updates the agency's thinking on how to ensure that medical devices are safe and effective for pediatric populations.
Historically, many medical devices and other medical products have been developed for adults, which constitute the largest market segment for many products. Many of those devices were approved based on data obtained from testing in adults, but few were backed by use data in pediatric patients, meaning healthcare providers and regulators had little data to determine if a product was safe or effective for use in children.
Regulators and legislators have taken a number of steps over the years meant to improve the quality and quantity of pediatric data they receive from sponsors of medical devices. In 2001, the passage of the Children's Health Act established requirements for protecting pediatric participants in clinical trials.
In 2007, Section 515A of the Food and Drug Administration Amendments Act (FDAAA) required any sponsor of a premarket application (PMA), humanitarian device exemption (HDE) or product development protocol (PDP) to submit information to FDA regarding how many pediatric patients are affected by the disease or condition their product is intended to treat.
And in 2013, Title V of the Food and Drug Administration Safety and Innovation Act (FDASIA) established new requirements intended to ensure that pediatric studies are actually completed.
But FDA's new guidance document, Premarket Assessment of Pediatric Medical Devices, focused on yet another law: the Medical Device User Fee and Modernization Act (MDUFMA) of 2002.
MDUFMA included provisions intended to promote the development of pediatric devices, such as exempting products intended to treat pediatric conditions from user fees, requiring pediatric experts to serve on advisory committees "where appropriate," requiring guidance on the types of information needed to assure the safety and efficacy of pediatric devices, and guidance on protecting children who participate in device trials.
FDA's guidance is intended to clarify three points, it said:
- to help define the pediatric population and pediatric use for medical devices
- to help identify the types of information needed to provide reasonable assurance of the safety and effectiveness of medical devices intended for use in the pediatric population
- to help define the guiding principles and protections sponsors should consider for pediatric subjects in device clinical trials
For example, the guidance defines pediatric subgroups as newborns (birth to one month of age), infant (1 month to two years), child (two to 12 years) and adolescent (12 through 21). While FDA conceded that including 21-year-olds in its definition was controversial and in some senses "arbitrary," it said that doing so "may be useful for some devices and device clinical trials."
"The subject's weight, body size, physiological development, neurological development, and neuromuscular coordination may often be more appropriate indicators than chronological age," the agency wrote.
Other sub-populations include patients with a low birth weight (less than 2.5 Kg), very low birth weight (less than 1.5 Kg), and preadolescents (11-13 years). These populations should be addressed in device labeling "as applicable," FDA said.
Much of the guidance focuses on the data sponsors of devices need to generate to actually illustrate that their products are safe for pediatric patients.
In general, FDA says, that evidence isn't conceptually different than that collected for adults. Companies will still need to assess the devices clinically and implement regulatory controls with respect to biocompatibility, sterility, environmental factors, and manufacturing.
But where pediatric trials differ is with the patients themselves. As the saying goes: Children are not tiny adults. They have markedly different physical characteristics, and companies need to take into account height, weight, growth, development, diseases, hormonal influence, anatomical/physiological differences, maturity, activity and immune status.
However, "Given the wide spectrum of devices, the necessary pre-clinical testing may vary considerably," FDA notes in its guidance. For example, some devices-new ones approved via the PMA pathway-will require new clinical evidence. Others, such as those cleared through the premarket notification pathway, will not. FDA said it is committed to the "least burdensome" principle of testing, which it explicitly stated applies to pediatric device testing.
For example, some devices are simply modified slightly to accommodate pediatric needs, such as an airway tube that is narrower than the adult version. "To support the modifications, the manufacturer should conduct a risk analysis of the changes and develop methods to adequately address or mitigate the identified risks," FDA explained. "This may require verification testing alone, or validation testing may be needed in the intended pediatric population."
Companies should also operate in such a way as to mitigate the risks to any children during development and testing.
The guidance also delves into how to take "unique host characteristics," such as age and size, into account, and lists dozens of factors to consider.
Labeling, study design considerations and trial protection procedures are also discussed at length.
Premarket Assessment of Pediatric Medical Devices