United States: The Interplay Between The FDA Regulatory Process For Medical Devices And Patent Law – FDA Premarket Review Of Medical Devices

1. Introduction

The medical device industry plays a crucial role in developing new medical technologies that can improve the ability to diagnose and treat illnesses. The United States is the world's largest medical device market. Like prescription drugs in the U.S., medical devices are regulated by the Food and Drug Administration (FDA). The regulatory process for medical devices is designed to balance two goals: 1) promoting novel and better devices; and 2) ensuring that the medical devices allowed to be introduced to the market are safe and effective.

Like many other competitive industries that rely on innovation, patent protection is crucial for medical device companies. Obtaining a patent that covers a medical device awards the manufacturer a limited monopoly to market the device and allows them to recover the high upfront costs incurred during the R&D and regulatory review.  Many medical device companies have separate teams dealing with FDA regulatory issues and patent protection. In certain circumstances, even sophisticated organizations may fail to adequately consider the interplay between the FDA regulatory process and patent law to safeguard their intellectual property rights. This article presents a brief overview of the FDA regulatory scheme of medical devices to provide the context for patent considerations. In the next article, we will discuss some implications FDA submissions may have on medical device patent rights, with some strategic considerations for medical device companies.

II. FDA's premarket review of medical devices

A. Risk-based classification and corresponding regulatory pathway

Medical devices encompass numerous devices, including diagnostic instruments, surgical tools and equipment, drug and food delivery devices and systems, vital sign monitoring equipment, prostheses and implants, and many others. The first step toward obtaining FDA permission to market is the classification of the medical device. The FDA categorizes medical devices into three classes – Class I, II, or III – based on their risks to the user, summarized in Table 1 below.

Table 1. Risk-based classification and corresponding regulatory pathway for medical devices.

It is important for the medical device company to decide on a proper classification of a new device early on because the classification will determine the regulatory pathway that, in many ways, determines the time and cost necessary (including the type and rigor of preclinical and clinical evidence) to obtain FDA permission to market.

The medical device company itself can determine classification by using the FDA's product classification database (https://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfpcd/classification.cfm) or by finding the matching description of the device in FDA's regulations on the classification of different types of devices. If the medical device company would like a formal device determination or classification from the FDA, the medical device company can consider submitting a formal request for information to the FDA.

Almost all Class I devices and some Class II devices are exempt from 510(k) clearance, subject to certain limitations. Most Class II devices require 510(k) clearance, and almost all Class III devices and some Class II devices require Premarket Approval Application (PMA). PMA is far more cumbersome than 510(k) clearance and is usually both expensive and time-consuming. This is because considering the high risk of injury or death associated with Class III devices, PMA requires extensive investigation and clinical trials to demonstrate a Class III device's safety and effectiveness. Therefore, certain medical device companies prefer the 510(k) pathway, as reflected by FDA's filing statistics—each year, the FDA receives approximately 40-80 PMAs and about four thousands 510(k)s. In other words, 510(k) clearance dominates the market entry of U.S. medical devices.

B. 510(k) clearance dominates the market entry of U.S. medical devices

1. 510(k) in a nutshell

The 510(k) is a premarket submission made to FDA to demonstrate that the new device to be marketed is as safe and effective, that is, substantially equivalent, to a legally marketed device. A legally marketed device is a device that (1) was legally marketed prior to May 28, 1976, or (2) was reclassified from Class III to Class II or I, or (3) was found substantially equivalent through the 510(k) process. The legally marketed device is also referred to as a "predicate device." Once the FDA determines the new device is substantially equivalent to a predicate device, the new device can then be marketed in the U.S. This determination is usually made within 90 days based on the information submitted by the submitter.

A claim of substantial equivalence does not mean the new and predicate device needs to be identical. A device is substantially equivalent if, in comparison to a predicate device, it either:

1. has the same intended use as the predicate device; and has the same technological characteristics as the predicate device; or
2. has the same intended use as the predicate device; and has different technological characteristics and does not raise different questions of safety and effectiveness; and the information submitted to FDA demonstrates that the device is as safe and effective as the predicate device.

Based on information submitted by the 501(k) applicant, FDA first determines that the new and predicate devices have the same intended use and any differences in technological characteristics do not raise different questions of safety and effectiveness. FDA then determines whether the new device is as safe and effective as the predicate device by reviewing the scientific methods used to evaluate differences in technological characteristics and performance data. This performance data can include clinical data and non-clinical bench performance data, including engineering performance testing, sterility, electromagnetic compatibility, software validation, biocompatibility evaluation, among other data.

2. 510(k) submission and availability to the public

The 510(k) submission must include a summary that must be in sufficient detail to provide a basis for determination of substantial equivalence with a predicate device. For example, the summary must include an identification of the predicate device to which the submitter claims equivalence and a summary of the technological characteristics of the new device in comparison to those of the predicate device. Furthermore, if the new device has undergone a "significant change or modification" that could significantly affect the safety or effectiveness of the device, then the 510(k) submission must include supporting data to show what the effects of the modification might be.

When the 510(k) application is cleared, the FDA publishes the decision on their website. The FDA also publishes the 510(k) summary by the fifth of the month following clearance, and further supporting information is available upon request made to the FDA under the Freedom of Information Act (FOIA).

C. PMA in a Nutshell

PMA is the most stringent regulatory pathway and PMA approval is given after FDA determines that the PMA contains sufficient valid scientific evidence to reasonably assure that the device is safe and effective. Because of the high risk of injury or death to the user, most Class III devices must undergo the PMA pathway. Many of these devices are first-of-a-kind devices made by innovative medical device companies.

The PMA must include data and scientific analysis based on sound scientific reasoning to support the safety and effectiveness of the device. For example, the PMA application must include a summary of the nonclinical laboratory studies with the device and supporting data and information. The PMA application must also include a summary of the clinical investigations involving human subjects with the device and supporting data. Further, the PMA application must include a concluding discussion demonstrating that the data and information in the application constitute valid scientific evidence and provide reasonable assurance that the device is safe and effective for its intended use. The concluding discussion should present benefit and risk considerations related to the device, including a discussion of any adverse effects of the device on health and any proposed additional studies or surveillance the applicant intends to conduct following approval of the PMA.

The FDA review of a PMA can take up to 6 months, and may take longer. FDA will notify the public of its decision to approve a PMA by making available, via FDA's Devices Approved page (https://www.fda.gov/medical-devices/recently-approved-devices/2020-device-approvals), a summary of the safety and effectiveness data upon which the approval is based. The summary will include information about any adverse effects of the device on health. The announcement also provides the applicant and other interested persons an opportunity for administrative review of the FDA approval. On a quarterly basis, FDA will publish a list of approvals announced during that quarter in the Federal Register. When a notice of approval is published, data and information in the PMA file will be available for public disclosure.

Because of the extensive nonclinical and clinical investigations required to prepare a PMA and the rigorous scientific review by the FDA, the PMA pathway is time-consuming and costly. However, the PMA pathway does offer additional protection to innovative medical device companies in that medical devices approved under the PMA pathway cannot be used as a predicate in a 510(k). This ensures follow-up devices from competitors have the same high threshold to cross before entering the market.

III. Conclusion

This article provides a brief overview of FDA's classification and corresponding premarket review process for medical devices. Navigating the FDA premarket review process is a challenge faced by medical device companies, who typically employ or consult with a group of specialized personnel to prepare and file FDA regulatory submissions. However, for medical devices, patent law and FDA regulatory review process can have considerable interplay. In the next article, we will discuss some implications 510(k) submission may have on medical device patent rights and patent infringement, with some considerations for 510(k) submission.

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