Opening Doors, a sign with the US flag and the word "Store", inbetween the opening doors a cd with sparkles, symbolizing US Market Access

Market Access for Medical Software in the United States

Market access for medical devices in the USA differs considerably from the European model. In Europe the manufacturer declares the conformity of his products with the legal requirements. Medical devices in the USA are in the competence of the federal agency FDA (Food and Drug Administration). Within the FDA, the Center for Devices and Radiological Health (CDRH) is responsible for the premarket approval and monitoring of medical devices.

In this blog post we are explaining which ways of market access for medical software exist in the USA and how the FDA tries to make innovations possible despite regulation.

The following figure shows you an overview of existing routes for market access of medical devices in the USA.

Overview of U.S. Market Access Routes

Step1: Is my Software a Medical Device?

As in Europe, the manufacturer must first clarify whether the product is a medical device according to the legal definition. For this you compare the intended use of your product with the definition in the 21 U.S. Code § 321h of the FD&C Act:

“The term “device” […] means 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. The term “device” does not include software functions excluded pursuant to section 360j(o) of this title.”

This definition is not so different from the one for a medical device in the EU MDR. It is noteworthy that software is not explicitly mentioned but nevertheless included.

Particular interest should be directed on the introduction of software-related adoptions of the 21st Century Cures Act as part of the U.S. Digital Health program. In more detail, it holds

  • an updated procedure for recognition of standards by the FDA leading to faster adaption of the state of the art (technical, quality),
  • continuous de-regulation procedure for class I and II devices established leading to a higher flux in (innovative) device categories, involving a process to update the classification panels,
  • newly announced relevant guidelines (for 510(k) submission),
  • accessories classified on their own and
  • software that will be out of bounds for FDA under the act, i.e.
    • administrative-support software,
    • health lifestyle software,
    • electronic patient records,
    • software to transfer, store or display test lab data and other device data, and
    • clinical decision support software that is not intended to acquire, process, or analyze a medical image or a signal from an IVD or a pattern or signal from a signal acquisition system.

Step 2: What Risk Class Does my Medical Device Belong to?

The next step is – as in Europe – the risk classification of the product.

Note, that the assignment to class I, II or III (low to high risk) is not carried out by the manufacturer but by the FDA!

The FDA uses a list that was drawn up based on medical devices available on the market on 28 May 1976 for assigning a risk class to your device. The list is organized in 16 so-called “classification panels” (21 CFR, Parts 862-892). For each device you will find information as its description, use context and classification. If no assignment is possible, your device ends up automatically with class III.

Try it yourself and search the classification database for the name (or part of it) of your medical device.  For example, the search for “software” in the database field “device” results in 40 entries ranging mainly from class I to II.

Step 3: Select the Appropriate Route to Market Access

The risk class determines, how manufacturer can achieve FDA clearance for market access for their product. Usually, class I and II device without exemptions require a premarket notification (PMN, also called (510(k)) and class III devices need a premarket approval (PMA).

General controls apply for all risk classes except for exempted devices. These include premarket submission, registration and listing of the medical device, as well as compliance with current good manufacturing practice (CGMP). To which extend CGMP requirements have to be fulfilled depends also on the risk class.

Certain low risk medical devices are “exempted” by the FDA, i.e. these devices require no premarket notification and / or compliance with quality system requirements. You find a list of medical devices exempted from 510(k) and CGMP on the FDA website.

510(k) (PMN) for Low to Middle-Risk Medical Devices

In the center of the submission of a 510(k) notification is the demonstration of substantial equivalence to a predicate device, i.e. this device must have been marketed before 1976 or it was cleared by the FDA having the same intended use. Essentially, you must compare the performance characteristics of your device with the ones of the predicate device to prove substantial equivalence. A major advantage of this route is that you are usually not required to provide clinical data for the demonstration of device safety and effectiveness.

Note, that you as manufacturer select the predicate device, but the final decision is up to the FDA. 

This route is also open for already marketed medical devices that should be used for another indication or of which the design has significantly changed.

The manufacturer can choose between 3 types of PMN (510(k)):

  • the traditional,
  • the special, and
  • the abbreviated PMN.

Traditional 510(k) Submission

This 510(k) type for market access requires several elements identified in 21 CFR Part 807.87. Among others these include:

  • name of device,
  • description of the device,
  • comparison with predicate device(s),
  • intended use of the device, as well as
  • proposed label, labeling, advertisements for the device and directions for use.

Compared to the PMA process, 510(k) means less effort for the manufacturer:

  • Clinical studies are not required although pre-clinical data are usually included in the submission.
  • Premarket inspections by the FDA are not occurring.
  • Also, in case of unsafe or ineffective 510(k) medical devices the FDA cannot easily withdraw the clearance.

Moreover, the 510(k) process generates less costs for the manufacturer. Already the fees for the FDA review differ significantly between the different routes to market access.

Note: The FDA recently limited the extend on valid claims of a predicate device to a timeframe no longer than 10 years.

What Happens After the Traditional 510(k) Submission?

After conducting the review of the 510(k) submission the FDA may take different actions as depicted in the following figure.

Actions taken by FDA after 510k Submission

Abbreviated and Special 510(k) Submission for Faster Market Access

The intention of these routes is to simplify the 510(k) submission for certain medical devices. Taking the abbreviated 510(k) you must consider following special FDA guidance documents or even applying certain (recognized) consensus standards. The review process by the FDA takes only 60 days.

Do you have a modified medical device already cleared under the 510(k)? Then the special 510(k) may be interesting for you. You do not have to provide data in this submission, but you are obliged to include information about the actions taken for design control. This review process usually takes only 30 days.

Software Change of Existing Device are Sometimes up to 510(k) Submission

Software modifications of existing devices may significantly affect the safety or effectiveness of a device or change its intended use. Modifications that trigger a premarket submission introduce new or modify previously identified risks, relate to risk controls or affect significantly clinical functionality or performance. To find out whether a new 510(k) is necessary you should answer the respective questions of this FDA guidance.

Novel Medical Devices can Gain Market Access via De Novo

The “De Novo” route was introduced 1997 for novel medical device without a predicate device. Remember that these devices are usually designated to risk class III which is associated with significant efforts for market access. After submission of a traditional 510(k) you can request a re-classification of your device to I or II. Or you submit a De Novo without preceding 510(k). Anyway, note the corresponding FDA guidance!

Breakthrough Device Designation Program

Under the following circumstances the Breakthrough Device Designation may be granted by the FDA:

  • the device must represent a breakthrough technology,
  • there must be no approved or cleared alternatives,
  • the device must offer significant advantages over existing approved or cleared alternatives or
  • the availability of the device is in the best interest of patients.

As a result of the designation the manufacturer benefits from intensive interaction and guidance by the FDA. In particular, this can be helpful in combination with the “De Novo” route.

PMA for New and High-risk Medical Devices

The most elaborate route for market access is PMA. You must submit various items to obtain PMA approval for market access:

  • name of device,
  • description of the device (including market history),
  • intended use of the device,
  • description of manufacturing process,
  • reports with conclusions drawn from pre-clinical and clinical studies, and
  • proposed label, labeling, and advertisements for the device and directions for use.

Note, for conducting a premarket medical device clinical trial you must obtain an investigational device exemption (IDE).

In contrast to 510(k) premarket inspections by the FDA are occurring. It takes 45 days for the initial check for completeness by the FDA and another 75 days for the initial review. After this the FDA may involve an advisory committee. Often the total review time of 180 days is exceeded.

Note, that changes to medical device with PMA approval require the submission of PMA supplements.

Particularities in Software Premarket Submissions

The FDA has summarized the content of premarket submissions for software in a separate guidance document. It applies to all of the above described types. In general, the extend of the documentation to be submitted is proportional to the so-called “level of concern” (minor, moderate and major) of the software.

Future FDA Approach for Market Access of Medical Software

There is a need for new approaches for market access of medical software. Development differs significantly from other medical devices and, more important, new versions are released more quickly. Anyhow, in the case of adverse events a medical software can be revised much faster.

The FDA started in 2017 to develop the so-called Software Precertification (Pre-Cert) Program seeking to allow faster market access for new medical software and to assure safety and effectiveness at the same time.

Note, that the Pre-Cert program addresses only software as a medical device (SaMD) also called stand-alone software and not software being part of a hardware medical device.

A pre-requisite for the participation in the program is the demonstration of “culture of quality and organizational excellence” principles to the FDA.

Excellence Principles FDA Pre-Cert

Currently, it is unclear whether recognized consensus standards play a role in this respect.

Pre-certified companies shall gain market access for medical software without premarket review. Until now nine companies are participating in the pilot program and, thus, agreed:

  • allowing on-site FDA inspections,
  • providing information of their quality management, and
  • providing post-market surveillance data.

Note, that companies participating in the Pre-Cert Program benefit from reduced premarket requirements, but greater efforts must be made with the post-market surveillance.

Our perspective regarding Pre-Cert is that FDA finishes the development of the model in revision 2.0 by the end of 2019. After gaining experience, the model may be opened afterwards for new participants eventually.

Mobile Medical Apps

The FDA applies the same risk-based approach to medical apps as to other medical devices. The focus lies on apps as an accessory to a regulated medical device or on apps transforming a mobile platform into a medical device. In a recent guidance on medical apps the FDA differentiates between apps being a medical device or not and provides a regulatory overview.

If you are interested in market access of a medical app we advise you to check out the interactive tool of the U.S. Federal Trade Commission (FTC).

The Role of Recognized Consensus Standards

Beside developing own performance or consensus standards the FDA recognizes consensus standards developed by external standardization organizations. Manufacturers are encouraged to use consensus standards. You will find a database of recognized consensus standards on the FDA website. Currently, 87 standards are assigned to software. Not all standards are fully recognized, i.e. the application of these standards fulfills the requirements laid down by the FDA only partly. If you declare the conformity with consensus standards you need to include inter alia the following information according to an FDA guidance:

  • identify the applicable consensus standards,
  • specify the requirements of the respective consensus standards that were met,
  • where appropriate identify any non-applicable requirement or adaptations of the standard and specify existing differences between tested and to be marketed devices, and
  • provide name and address of involved laboratory or certification bodies.

Our Recommendations

In this article we have compiled the established and proposed new routes for market access of medical devices including software in the U.S. Our recommendations are:

  • Understand the fundamental differences between a real approval process in the USA and the European system.
  • Follow step by step the route for market access as indicated above.
  • Check whether certain activities and documentations for the market access in the USA and Europe resemble each other and can be addressed in one process in your company.
  • Constantly monitor the respective FDA databases for the release of new guidance documents and recognized consensus standards.
  • Be aware of post-market regulations for certain class II and III devices of the FDA.