The Ultimate Guide to the FDA Premarket Submission Process

Our Senior FDA Compliance Lawyers and Consultants Demystify the Pre-Market Submission Process

Many types of companies need to comply with the U.S. Food and Drug Administration’s (FDA) pre-market submission process. While not all FDA-regulated products require pre-market submissions, many do, and failing to make a required submission can lead to FDA scrutiny and costly penalties.

But, failing to make a required pre-market submission isn’t the only mistake that manufacturers, importers, and other companies need to avoid. Mistakes made during the pre-market submission process can have costly consequences as well. Avoiding these mistakes starts with identifying the relevant pre-market submission process and gaining a clear understanding of the rules, requirements, and prohibitions that apply.

Choosing the Correct Type of Pre-Market Submission

The FDA has six separate pre-market submission programs. Each of these programs is unique, and each is available for use under different circumstances. Here is a brief introduction to each program and the types of products it covers:

1. Pre-Market Notifications (510(k) Submissions)

The FDA’s premarket notification process allows medical device companies to bring new products to market without going through the FDA’s more rigorous pre-market approval (PMA) process, which is discussed below. Any Class I, II, or III device intended for human use that does not require premarket approval must submit a 510k submission unless exempt.As the FDA explains, a pre-market notification is the appropriate means of submission when the notification is sufficient to “demonstrate the device to be marketed is as safe and effective, that is, substantially equivalent, to a legally marketed device.” Class I, Class II, and Class III devices can all potentially be eligible for pre-market notification submissions (also known as 510(k) submissions), though determining the appropriate submission process for a device requires a case-by-case assessment.When using a 510k submission, marketers have to compare their device to a similar legally marketed devices, which qualify as predicates, and provide evidence that prove the device to be substantially equivalent. The device cannot be brought to market until the FDA issues a letter determining the device substantially equivalent to the devices legally marketed, or the predicates.

2. 510(k) Third Party Review Program Submissions

The FDA’s 510(k) Third Party Review Program is an available alternative to a traditional 510(k) submission in some cases. Specifically, Third Party Review is an option for “certain low-to-moderate risk medical devices,” which also requires a case-by-case assessment. As the FDA also explains, “Under the Third Party Review Program, a 510(k) submission for an eligible device may first be submitted to an accredited 3P510k Review Organization rather than directly to the FDA . . . . [and] 3P510k Review Organizations use the same criteria used by the FDA to review 510(k) submissions.” While 510(k) Third Party Review Program submissions are often quicker than traditional 510(k) submissions, the FDA ultimately makes the final decision based on the 3P510k Review Organization’s recommendations.

3. Pre-Market Approval (PMA) Applications

Pre-market approval (PMA) is required for most Class III medical devices and all new drugs manufactured and/or sold in the United States. Pre-market approval is a lengthy process that requires clear documentation of compliance with all applicable federal laws and regulations, including the FDA’s Current Good Manufacturing Practice (CGMP) regulations for pharmaceutical applications. As the FDA makes clear, “PMA is the most stringent type of device marketing application required by FDA . . . . [and] PMA approval is based on a determination by FDA that the PMA contains sufficient valid scientific evidence to assure that the device is safe and effective for its intended use(s).”

4. De Novo Classification Requests

The FDA’s De Novo classification request process allows medical device manufacturers to bring eligible Class I and II devices to market without a PMA submission even when there is no substantially equivalent device on the market. The FDA describes the De Novo classification request as a “risk-based classification process,” that is an option for Class I and II devices, “for which general controls alone, or general and special controls, provide reasonable assurance of safety and effectiveness for the intended use, but for which there is no legally marketed predicate device.” Manufacturers can use the De Novo submission process either: (i) without first submitting a 510(k) pre-market notification; or, (ii) after receiving a not substantially equivalent (NSE) notice from the FDA in response to a 510(k) notification.

5. Humanitarian Device Exemption (HDE) Submissions

The FDA’s Humanitarian Device Exemption (HDE) program applies to qualifying devices, including Humanitarian Use Devices (HUDs) that are, “intended to benefit patients in the treatment or diagnosis of diseases or conditions that affect or are manifested in not more than 8,000 individuals in the United States per year.” As the FDA notes, its review of HDE applications “has similarities to the review of PMA applications, with a few key differences.” Most significantly, HDE applications are exempt from the requirement to establish a reasonable assurance of effectiveness, which is required for all PMA applications.

6. Investigational Device Exemption (IDE) Submissions

The Investigational Device Exemption (IDE) to the PMA submission process is available for devices that are intended to be used strictly in clinical research. As the FDA explains, “[a] n approved IDE permits a device to be shipped lawfully for the purpose of conducting investigations of the device without complying with other requirements of the Food, Drug, and Cosmetic Act (FD&C Act) that would apply to devices in commercial distribution.” However, the FDA’s Good Clinical Practices (GCP) still apply to the device.

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Navigating the Relevant Pre-Market Submission Process

As noted above, each of the FDA’s pre-market submission procedures is unique, and each could fill an “Ultimate Guide” of its own. For purposes of this Ultimate Guide, however, we’ll cover the basics of deciding which pre-market submission process to use and how to begin the submission process:

• Identifying the Most Appropriate Pre-Market Submission Process – In some cases, companies will have the ability to choose between multiple pre-market submission processes. Choosing the most advantageous process based on the nature of the device (among other pertinent considerations) is key to coming to market as quickly and cost-effectively as possible. 
• Identifying All Relevant Federal Laws and Regulations – Once a pre-market submission process has been chosen, the next step is to identify all federal laws and regulations that are relevant to that particular submission process. 
• Developing and Implementing Submission-Oriented Compliance Policies and Procedures – With a clear understanding of the applicable laws and regulations, the company can then develop custom-tailored policies and procedures that are focused specifically on meeting the relevant submission requirements. 
• Documenting Compliance with All Pertinent Statutory and Regulatory Requirements – Along with meeting all pertinent statutory and regulatory requirements, documenting this compliance is also essential for avoiding issues with the FDA (and resolving any issues, if necessary). 
• Preparing the Pre-Market Submission – Next comes preparing the pre-market submission itself. This, too, is a complex process that requires a custom-tailored and detail-oriented approach based on a clear understanding of all relevant rules and requirements. 
• Preparing to Work with the FDA (or 3P510K Review Organization) – After filing their submissions, companies should be prepared to work with the FDA (or 3P510K Review Organization) throughout the pre-market review process. 
• Addressing Any Issues and Closing the Pre-Market Submission Process – Finally, companies should work with their counsel to resolve any issues that arise and close the pre-market submission process. Once the process is complete, they will then need to focus on managing post-market compliance on an ongoing basis. 

Will the FDA Conduct an Inspection?

The FDA conducts inspections as part of the pre-market review process in some (but not all) cases. If the FDA will be conducting an inspection in connection with your company’s pre-market submission, it will be critical to ensure that your company and personnel are thoroughly prepared. At Oberheiden P.C., our lawyers and consultants have extensive experience guiding companies through all stages of the pre-market submission process—including FDA inspections—and we can provide the advice and insights you need to help ensure that the process goes as smoothly as possible.

FAQs: Finding Success with FDA Pre-Market Submissions