Regulatory Pathway Defines the Need for a Clinical Study

by | May 11, 2021 | ClinReg Strategy

You are developing a medical device that addresses a clinical need, but how do you get it into the hands of physicians to improve the lives of patients? In this article, we discuss the most common FDA pathways to market clearance and share a few insights to help you determine the optimal regulatory path for your device.

Intended Use, Indications for Use & Product Classification

Before you can select your optimal regulatory pathway, it is necessary to determine your product classification and associated risk level. To begin, you will need to define how your product addresses a clinical need. The intended use is the general purpose of the device or its function. The indications for use statement describes the disease or condition the device will diagnose, treat, prevent, cure or mitigate. This statement defines the patient population for which the device is intended.

The nuances in these statements are important. If they are too general, they may over-simplify your product and not clearly explain its use; however, if they are too specific, they may narrow your potential patient population and may require supporting clinical data. The FDA guidance document General/Specific Intended Use provides useful information on defining your intended use and indications for use statements.

Next, you will need to align your product intended use and indications for use statements with established classification categories in the Code of Federal Regulations (CFR). The FDA Device Classification Panels web page and the FDA classification database will help you determine the appropriate classification for your product and the associated risk level of Class I (low), Class II (intermediate), or Class III (high).

FDA Medical Device Regulatory Pathways & Clinical Data Requirements

The FDA Center for Devices and Radiological Health (CDRH) oversees medical devices and provides multiple pathways for achieving market authorization. While there are several exemptions, this blog post focuses on the three most common regulatory submission pathways, namely: 510(k), premarket approval (PMA), and De Novo.

In a nutshell, a 510(k) relies on showing comparability to existing technology and often does not require clinical data. A PMA almost always requires some form of clinical data, and a De Novo is a hybrid of the two, so clinical data may or may not be required. An overview of these submission types is provided in Table 1, followed by a deeper dive into each submission type.

Table 1. Most Common FDA Submission Types
510(k) [or exempt] or De NovoPMA
ClassificationClass IClass II Class III
ControlsGeneral controls, with provisions pertaining to:
• Adulteration (bad product)
• Misbranding (unsupported claim)
• Registration & listing
• Premarket notification (510(k))
• Banned devices
• Notification & repair, replacement & refund
• Records & reports
• Restricted devices
• Good manufacturing practices (GMP)
General + special controls, the latter of which are usually device-specific and may include the following:
• Performance standards
• Postmarket surveillance
• Patient registries
• Special labeling requirements
• Guidelines
• Premarket data requirements
o Bench, biocompatibility, & animal
o Clinical (if applicable)
General and special control are insufficient to provide reasonable assurance of safety and effectiveness; PMA required
Clinical data required?NoSometimes (10-15%)Almost always


The premarket notification, commonly referred to as a 510(k) submission, is the FDA pathway for medical devices that are low to moderate risk. The 510(k) clearance is granted when it is demonstrated that a subject device is “substantially equivalent” to a predicate device. In other words, a 510(k) relies on data that shows comparability to currently marketed product with the same intended use and fundamental technology.  

In addition to general controls, which are applicable to all products (class I, II and III), some types of 510(k)-eligible class II devices also require special controls. For example, the FDA has a class II special controls guidance document for certain percutaneous transluminal coronary angioplasty (PTCA) catheters. Special controls usually comprise requirements for device-specific performance standards, special labeling, preclinical test data, human clinical data, patient registries, and post-market surveillance.  

While many 510(k) submissions do not require human clinical data, some do. If the manufacturer of a predicate device to which you are demonstrating substantial equivalence used clinical data to support its 510(k) clearance, you may also need clinical data. Another scenario that may require clinical data is if you are expanding your indications for use from a general indication to a more specific indication.

Premarket Approval (PMA) 

The PMA process is required for class III devices and entails the highest and most stringent level of FDA oversight. A product is assigned to this category if it is life-supporting or life-sustaining; for a use that is of substantial importance in preventing impairment of human health; or if it presents a potential unreasonable risk of illness or injury.  

Regardless of whether your product is the first of its kind or a new version of an already established device type, if it fits in the PMA category, you will need data to demonstrate the clinical safety and effectiveness of your device. Paired with preclinical data, human clinical data is an essential component of PMA applications.  

If your class III device is both high risk and novel, keep in mind that you may need a series of clinical studies to establish the safety and effectiveness profile, starting with a first-in-human or other early feasibility clinical evaluation. 

De Novo 

The De Novo process, a hybrid of the 510(k) and PMA pathways, is ideal for low- to moderate-risk novel or innovative devices that do not have a viable predicate device option for a 510(k). A De Novo submission is granted if a “reasonable assurance of safety and effectiveness” can be demonstrated for the device. This may be achieved through preclinical bench, biocompatibility, and animal data. If your device is novel, a human clinical study may also be required. Note: this clinical data may be useful for product adoption in the field or as a barrier to market for competitors who could use your granted De Novo market authorization as their predicate device. 

As discussed in a previous blog post, the FDA pre-submission program is a great free and voluntary way to get feedback about your proposed regulatory pathway, your preclinical test plans, and your clinical study strategy, especially when it comes to more complicated devices, unique patient populations, and creative clinical study designs. FDA strongly recommends a pre-sub for those considering the De Novo pathway.  

Next Steps  

Regulatory pathways can be complex, and the strategy you choose has huge ramifications because it determines your product test requirements and clinical study needs. You’ll want to give careful consideration to this strategy at the beginning of your product development process.  

After you’ve selected your regulatory pathway and determined the need for human clinical data, it’s time to begin thinking about clinical study design. While some might think it is unfortunate that there are no hard and fast rules, we think this gray area affords you flexibility and control over your clinical strategy. Stay tuned for more BRIGHT Insights to aid in smart study design. 

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