Introduction to Regulatory Considerations when Launching VR Solutions in the U.S.

Guest Contribution to VRforHealth

“Introduction to regulatory considerations when launching VR solutions in the US” is the first of a series of contributions from external experts excited to participate in the educational mission of VRforHealth. If virtual reality technology is consolidating its status for wellness and therapeutic uses, it is thanks to the efforts of academic researchers and clinicians, start-ups creating solutions, patients participating in research, regulatory officials who are reviewing the efficacy and tolerance of these solutions. We welcome guest authors from the “village” it takes to advance these new solutions.

The authors of this article are Hélène Louys and Pol-Antoine Hamon. Hélène Louys is a Doctor of Pharmacy and a lawyer, with 15 years of practical experience in both the regulation of health products globally and the practice of health law. Pol-Antoine Hamon is a hospital pharmacist and MBA with 20 years of experience in health product market access.

In this article, the authors describe the regulatory framework for commercializing VR solutions in the US. It includes: device categorization, application procedures, related definitions and the (rare) examples.

As our readers are aware, Virtual Reality (VR) is a technology that recreates an immersive or 3D environment through the combination of advanced software, hardware and design. VR can bring direct clinical benefits to people suffering from multiple conditions including pain, anxiety and other mental health challenges, and rehabilitation, as is demonstrated on the VRforHealth website in the curated video section.

VR solutions are considered medical devices in both the United States and Europe. What is a medical device?

If a VR solution is a device from a regulatory perspective, let’s define that term. “Device” is defined as an instrument, apparatus, implement, machine, contrivance, implant, in vitro reagent, or other similar or related article, including any component, part, or accessory, which is:
1.     recognized in the official National Formulary, or the United States Pharmacopeia, or any supplement to them,
2.     intended for use in the diagnosis of disease or other conditions, or in the cure, mitigation, treatment, or prevention of disease, in man or other animals, or
3.     intended to affect the structure or any function of the body of man or other animals, and which does not achieve its primary intended purposes through chemical action within or on the body of man or other animals and which is not dependent upon being metabolized for the achievement of its primary intended purposes.[1]
Secondly, medical devices are categorized in 3 classes: Class I, Class II and Class III [2]. Each class is defined by the intended use of the device and the indications for use. [3] The choice of the class is very important, as it will also determine how to proceed to market with the device[BS1] [LHI2].

Table from FDA: devices, regulatory controls and submission types (5)

The two major pathways of application procedure are pre-market notification (510(k)) and pre-market approval (primarily for class III devices). For a low or moderate risk device, the De Novo process[BS3] [LHI4]  may be an option. The De Novo application allows a sponsor to submit a request to the FDA to classify a device for which that sponsor believes there is no predicate device, without first submitting a 510(k) notification.

A 510(K) is a premarket submission made to FDA to demonstrate that the device to be marketed is as safe and effective, that is, substantially equivalent, to a legally marketed device (section 513(i)(1)(A) FD&C Act) that is not subject to premarket approval.

A predicate device (PD) is a medical device that may be legally marketed in the U.S, and used as a point of comparison for new medical devices seeking approval through FDA’s 510(k) premarket clearance pathway.
Regarding the content of the device dossier, the general requirements are:
–        Design control (each manufacturer of any class III or II and potentially class I shall establish and maintain procedures to control the design of the device[4]);
–        Non Clinical testing;
–        Clinical evidence;
–        Labeling.

VR solutions belong to Class II as demonstrated below. To illustrate the market submission options, we will focus on the first two and so far, only VR solutions authorized by FDA[BS5] [LHI6] [LHI7] .

EaseVRx, now RelieVRx, from AppliedVR is is the first therapeutic VR solution to be approved by the FDA, as a prescription-use immersive, virtual reality system intended to provide adjunctive treatment, based on cognitive behavioral therapy skills and other evidence-based behavioral methods for patients (age 18 and older) with a diagnosis of chronic lower back-pain (defined as moderate to severe pain lasting longer than three months). The device is intended for in-home use for the reduction of pain and pain interference associated with chronic lower back pain[6].

The FDA reviewed it through the De Novo premarket review pathway. In order to classify RelieVRx in class I or II, the proposed class had to succeed in terms of the regulatory controls[7] (see table above) [BS8] [LHI9] that would provide reasonable assurance of the safety and effectiveness of the device for its intended use[BS10] [LHI11] .
After reviewing the information submitted in the De Novo request, the FDA determined that, for the previously stated indications for use, RelieVRx can be classified as a class II device with the establishment of special controls for class II.
This action creates a new regulatory classification, which means that subsequent devices of the same type with the same intended use may go through the FDA’s 510(k) premarket process, wherein devices can obtain marketing authorization by demonstrating substantial equivalence to a predicate device[8].

It is also interesting to note that RelieVRx had been granted breakthrough device designation. The Breakthrough Devices Program offers manufacturers an opportunity to interact with the experts of the FDA Center for Devices and Radiological Health CDRH[9] through different program options to efficiently address topics as they arise during device development, evaluation and pre-market review. With status, manufacturers receive timely feedback and can expect a prioritized submission review[10].

In 2021, the CDRH granted 13 devices breakthrough designation. It reflects the dedication of the CDRH staff in helping industry bring innovative devices to market. It will be interesting to see in the coming years how many VR therapies will be authorized now that there is a predicate device (RelieVRx).
The second VR solution authorized to-date by FDA is InVisionOSTM. While it is a VR preoperative planning tool. and not a therapeutic solution, it is important to be aware of this FDA authorization. InVisionOSTM[BS12] [LHI13]  software automatically converts the patient’s computed tomography (CT) scan from any PACS system into a 3D reconstruction within seconds. Surgeons can then use the Oculus Quest 2 to view, manipulate and isolate relevant anatomical areas prior to performing the actual surgical procedure[11]. 
FDA issued on November 10, 2021, a 510(k) clearance for this pre-operative planning tool which is a pre-market notification process by which the FDA “clears” a medical device for marketing. In the premarketing notification process, the device sponsors must establish that their device is “substantially equivalent” to a legally marketed device. The legally marketed device to which equivalence is drawn, is known as the “predicate” device.

The device is subject to general provisions of the Act to be marketed which include requirements for annual registration, listing of devices, good manufacturing practice, labeling, and prohibitions against misbranding and adulteration[12].
The regulatory considerations do not stop once the VR solutions are marketed. Manufacturers, distributors, importers have obligations relative to quality systems requirements or Good Manufacturing Practices (GMP) but also relative to packaging and labeling requirement, vigilance and advertising.

Denise Silber, VRforHealth, thanks our guest authors for their contribution!

Footnoted References

[1] Section 201(h) of the Federal Food, Drug and Cosmetic Act (FD&C Act)
[2] 21 CFR Part 860
[3] FD&C Act 513, [360c], Classification of devices intended for human use; devices classes
[4] 21 CFR 820.30
[6] Classification order, EasyVRx, DEN210014
[7] General controls are regulatory requirements described in the following sections of the FD&C Act: 501 (Adulterated devices), 502 (Misbranded devices), 510 (Registration of producers of devices), 516 (Banned devices), 518 (Notifications and other remedies), 519 (Records and reports on devices), and 520 (General provisions respecting control of devices intended for human use).
Special controls are regulatory requirements for class II devices. FDA classifies into class II devices for which general controls alone are insufficient to provide reasonable assurance of the safety and effectiveness of the device, and for which there is sufficient information to establish special controls to provide such assurance.Special controls are usually device-specific and include: Performance standards, Postmarket surveillance, Patient registries, Special labeling requirements, Premarket data requirements, Guidelines.
[8] FDA News release, November 16, 2021: FDA authorizes marketing of virtual reality system for chronic pain reduction
[9] The US FDA regulates medical devices to assure their safety and effectiveness. The primary FDA center for managing the regulatory operations pertaining to medical devices is the Center for Devices and Radiological Health (CDRH). CDRH consists of several suboffices within FDA that are structured to manage different classes of medical devices.
[10] CDRH-2021- Annual Report
[12] InVisionOSTM, 510(k) clearance