The topic of custom implants and instruments generates excitement about the potential of new and innovative technology, especially for 3D printed devices. Numerous terms—including "patient-matched," "patient-specific," "customized," and "custom"—have been used to describe implants and instruments that are tailored to a specific patient's anatomy.
In the United States jurisdiction, however, the term "custom device" has a specific regulatory implication, which can create confusion about device-definitions and regulations.
Recently, the U.S. Food and Drug Administration (FDA) issued guidance regarding custom device exemptions. The guidance document summarizes how FDA typically regulates devices that are tailored to patient anatomy—so-called patient-matched or patient-specific devices—as follows:
"It is worth noting that FDA reviews, clears, and approves for marketing many patient-specific devices (also referred to as patient-matched devices). Patient-specific devices are, in general, ones in which ranges of different specifications have been approved or cleared to treat patient populations that can be studied clinically.
The guideline document goes on to state that "premarket submissions for such devices are sometimes referred to as 'envelope' submissions because their approval or clearance covers the entire range of specifications data they contain to support. The final manufacturing of these devices can be delayed until physicians provide imaging data or other information to the manufacturer to finalize device specifications within cleared or approved ranges. As a result, such devices are specifically tailored to patients."
In summary, patient-matched and patient-specific devices are fully regulated by the well-known 510(k) and premarket approval (PMA) pathways. This ensures the application of patient safeguards available under FDA's risk-based approach.
Examples of patient-specific and patient-matched medical devices include surgical cutting guides, joint arthroplasty implants, and trauma implants. For example, innovative, patient-matched guides manufactured by 3D printing are commercially available in the United States for the placement of pedicle screws in the thoracolumbar spine (Fig. 1) and for total knee arthroplasty (Fig. 2).
Having identified patient-specific devices as following a traditional regulatory pathway, the FDA guidance uses the example of a patient-specific arthroplasty device to draw an important distinction in language between patient-specific and custom devices, as follows: "For example, a manufacturer of an ankle replacement device could submit a 510(k) to cover a range of specifications for different system components to accommodate multiple patients with different anatomical characteristics. While some in industry have sometimes colloquially referred to these devices as 'customized,' they are not custom devices meeting the Food, Drug and Cosmetic Act custom device exemption requirements unless they comply with all of the criteria of section 520(b). Marketing applications are required for these device types because the devices and patient populations can be defined and studied."
This definition implies that a truly custom device is one for which the patient population cannot be defined and studied because the population is too small or the requirements are completely unique to one patient. Under certain circumstances, such devices may be partially exempt from some aspects of regulation.
Custom devices and custom device exemption
The same FDA guidance document clarifies when truly custom devices are partially exempt from regulatory requirements because the patient population cannot be identified and studied. The impetus for the guidance was the 2012 Food and Drug Administration Safety and Innovation Act, which required the implementation of changes to the custom device exemption and introduced the following three new concepts applicable to custom devices:
- the device is created to comply with the order of an individual physician
- multiple units are not to exceed five (5) per year
- annual reporting requirements must be met for such devices
The critical requirement for exempt custom devices is that no more than five units of a particular device type are manufactured per year. Specifically, this is interpreted to mean five new custom device patients per year, so bilateral devices are not counted twice.
Similarly, multiple implants manufactured for the same patient are not counted, so long as only one is implanted and the rest are discarded. Also, revisions of custom devices may not be counted against the tally so long as the revision fits the custom device criteria as well.
An example given by FDA of a potentially exempt custom device is a total hip replacement for a patient who has skeletal dysplasia resulting in short stature and deformity. Currently marketed implants would not address the patient's unique anatomy, and the population of patients with this condition would be too few to study. Another example would be a male patient who is 7' 2" tall and requires a total disk arthroplasty.
It is important to note that partial exemption from clinical studies for custom devices may be warranted due to the inability to define or study the patient population, however, such devices are still subject to multiple stringent regulations, including the following:
- quality system regulation
- design controls
- medical device reporting
- corrections and removals
- registration and listing
Compassionate and humanitarian use
A device that is currently unapproved or not cleared may be undergoing an investigational device exemption (IDE) trial. Such a trial will be authorized by the FDA for a specific patient population defined by a set of inclusion and exclusion criteria.
Under limited circumstances, a patient who is not a candidate for a custom implant may be able to receive the investigational implant, despite being outside the study population, as a one-time exception. This is termed compassionate use, also known as single patient/small group access. Importantly, the criteria for such use are narrow and include the presence of a serious disease for which there is no alternative treatment and prior approval from FDA for a device currently undergoing an IDE trial for some other indication.
Another regulatory pathway for small populations is the humanitarian use device. These devices are designed to treat diseases that affect fewer than 4,000 individuals per year in the United States. The rationale for this pathway is that a manufacturer's investment could exceed its returns for a small population.
To qualify for a humanitarian device exemption, the manufacturer submits to the FDA documentation similar to a traditional PMA application. Certain aspects of the efficacy criteria may be waived to mitigate the burden of full-scale, pivotal, phase III clinical trials. However, all other regulatory requirements apply, making the humanitarian-use designation distinct from a custom device or compassionate use.
S. Raymond Golish, MD, PhD, MBA, is chair of the AAOS Biomedical Engineering Committee. He can be reached at email@example.com
- U.S. Food and Drug Administration: Custom Device Exemption - Guidance for Industry and Food and Drug Administration Staff. 24-Sep-2014. [Accessed 05-Mar-2016].
- Krishnan SP, Dawood A, Richards R, Henckel J, Hart AJ: A review of rapid prototyped surgical guides for patient-specific total knee replacement. J Bone Joint Surg Br 2012;94(11):1457–1461. doi: 10.1302/0301-620X.94B11.29350.
- Center for Devices and Radiological Health (CDRH): Investigational Device Exemption (IDE) - IDE Early/Expanded Access." [Accessed 13-Mar-2016].
- CDRH: Humanitarian Device Exemption. [Accessed 13-Mar-2016]