Navigating the U.S. Food and Drug Administration (FDA) regulatory process can be one of the most challenging steps for medical device manufacturers aiming to enter the American market. Unlike the European system, where the CE marking process is guided by Notified Bodies under the Medical Device Regulation (MDR), the U.S. market is controlled by a centralised federal agency — the FDA. Understanding the different regulatory pathways — 510(k), De Novo, and PMA — is essential to selecting the right route for your product.

This article provides a practical guide for determining your FDA submission pathway, drawn from Educo Life Sciences’ training session US FDA Regulatory Strategies for Medical Devices & IVDs (Kathleen Harris, 2025).

 

Understanding FDA Device Classifications

Before choosing a submission route, you must first determine your device’s classification, which defines the level of regulatory control required to ensure safety and effectiveness.

The FDA recognises three classes under the Food, Drug, and Cosmetic Act (FD&C Act):

• Class I – General Controls: Low-risk devices such as wheelchairs or surgical gloves.
• Class II – General and Special Controls: Moderate-risk products like infusion pumps or surgical drapes.
• Class III – Premarket Approval (PMA): High-risk devices that support or sustain life, such as pacemakers or implantable heart valves.

Each class determines the extent of data, documentation, and FDA oversight needed. For instance, Class I devices may be exempt from certain manufacturing or pre-submission requirements, while Class III products undergo detailed scientific review.

In contrast to the European MDR, the U.S. system does not use Class IIa/IIb sub-categories. A product is either Class I, II, or III — simplifying the hierarchy but making accurate classification even more critical.

 

Step 1: Determine Your Product Classification

Your classification sets the foundation for your regulatory strategy. The quickest way to confirm it is through the FDA Product Classification Database, which identifies your product code, regulation number (21 CFR Parts 862–892), and whether it is exempt from certain controls.

If you are uncertain, the FDA offers a 513(g) Request for Classification. This formal process provides a binding determination of your device class within 60 days. As Kathleen Harris noted during training, “the 513(g) is there to protect you — it ensures that someone else in the agency can’t change their mind a year later”.

A typical 513(g) request costs US $7,301 (or US $3,650 for small businesses in FY 2025). For start-ups or new entrants to the U.S. market, this step can prevent months of uncertainty and costly misclassification.

 

Step 2: Check for Exemptions and Limitations

Many Class I and some Class II devices are exempt from 510(k) premarket notification. However, these exemptions come with strict limitations, detailed in section .9 of each 21 CFR regulation (e.g., 21 CFR 864.3600 for light microscopes).

For example:

• A basic light microscope is both 510(k) and GMP-exempt.
• But if software is added that interprets or transmits data, the exemption no longer applies.
• Similarly, if a product becomes sterile, it typically loses its exempt status.

As Harris highlighted, “All devices classified as exempt are subject to the limitations on exemptions. If you sterilise your product, it will not be exempt from GMP and it will not be exempt from 510(k)”.

Understanding these nuances prevents the common — and costly — mistake of assuming “Class I means no submission required.”

 

Step 3: Selecting the Right Regulatory Pathway

Once classification and exemptions are established, the next decision is which FDA submission route applies.

🔹 The 510(k) Pathway — Substantial Equivalence

A 510(k) is a premarket notification demonstrating that your device is substantially equivalent to an existing legally marketed device (known as the predicate).
Under Section 510(k) of the FD&C Act, manufacturers must notify the FDA of their intent to market a medical device and provide evidence of its safety and effectiveness compared with the predicate.

A key takeaway from the Educo training is that 510(k)s are cleared, not approved. Using the term “FDA approved” for a cleared product is illegal and can trigger enforcement action.

Typical timeline and cost:

• User fee (FY 2025): US $24,335 (US $6,084 for small businesses)
• Target review time: 90 days (average ≈ 163 review days in 2023)

Around 70 % of all devices entering the U.S. market follow this route.
The 510(k) process suits most Class II devices and some Class I products that are not exempt.

 

🔹 The De Novo Pathway — For Novel, Low-Risk Devices

If your device has no predicate but presents a low-to-moderate risk, the De Novo classification process provides a way forward.

This route allows you to submit a full technical package to FDA, including clinical and performance data, and propose how the device can be safely regulated under general and/or special controls.
If successful, the FDA will assign your product a new regulation number, effectively creating a new category that future manufacturers can cite as a predicate.

De Novo requests are becoming more common as biotechnology and AI-driven diagnostics expand beyond traditional device types.
In 2023, FDA cleared 17 De Novo requests, demonstrating how innovation is increasingly shaping U.S. regulatory policy.

Typical timeline and cost:

• User fee (FY 2025): US $162,235 (US $40,559 small business)
• Target review time: 150 review days

Harris summarised the process succinctly: “You are saying to FDA: this is innovative and new, but it’s not high-risk enough to be a Class III. Review our data and classify it appropriately”.

 

🔹 The PMA Pathway — For High-Risk, Class III Devices

Premarket Approval (PMA) is the most rigorous FDA pathway. It applies to Class III devices that support or sustain human life, are critical to health, or present potential risk of illness or injury.

Unlike 510(k), a PMA is a scientific and regulatory review to evaluate both safety and effectiveness. It includes clinical data, design validation, and manufacturing inspections.
PMA devices are formally approved by FDA — a legal distinction that grants additional liability protection to manufacturers.

Typical timeline and cost:

• User fee (FY 2025): US $540,783 (US $135,196 small business)
• Target review time: 180 review days (often 12–18 months overall)

Every new manufacturer submitting a PMA must undergo a PMA readiness inspection before the review begins. FDA then reinspects the facility at least once every 12 months, reflecting the high-risk nature of these products.

Examples include drug-eluting stents and HER2 IHC diagnostic systems, which require extensive evidence to demonstrate reliability and clinical benefit.

 

Step 4: Use Pre-Submission Tools to Your Advantage

The FDA encourages early engagement through several formal mechanisms:

• 513(g) Request – to confirm classification (as noted earlier).
• Request for Designation (RFD) – for combination products where drug, biologic, or device components overlap. This determines which FDA centre (CDER, CBER, or CDRH) leads the review.
  The RFD process takes 60 days and is free of charge.
• Q-Submissions / Pre-Subs – optional meetings with FDA reviewers to discuss testing strategies or documentation expectations.

Proactively using these tools helps companies avoid delays and demonstrates regulatory maturity.

 

Step 5: Prepare for Inspection and Post-Market Obligations

Once your product is cleared or approved, compliance doesn’t end there.

Manufacturing and Quality Systems

All Class II and III devices must comply with Good Manufacturing Practice (GMP) under 21 CFR Part 820, including design control, device history files, and validation activities.
Class I devices may be GMP-exempt, but any modification (such as sterilisation) removes that exemption.

Annual Establishment Registration and Listing

Every establishment that manufactures, imports, or distributes medical devices in the U.S. must register annually with FDA and list each device produced.
This requirement applies even to 510(k)-exempt devices.

• Fee (FY 2025): US $9,280 (no small business waiver).
• Renew every year between 1 October and 31 December.

Failure to renew or list accurately can lead to immediate marketing suspension.

 

Step 6: Plan Your Regulatory Budget and Timeline

Budgeting accurately for U.S. market entry is essential.
The table below summarises current FY 2025 FDA user fees and average review times:

Submission Type	Standard Fee (USD)	Small Business Fee (USD)	Typical Review Days
513(g) Request	7,301	3,650	60 days
510(k) Submission	24,335	6,084	163 review days
De Novo Request	162,235	40,559	150 review days
PMA Application	540,783	135,196	180 review days
Class III Annual Report	18,927	4,732	—
Establishment Registration	9,280	—	Annual

Source: FDA FY 2025 Medical Device User Fees; Educo Life Sciences training materials.

Note that fees increase annually on 1 October, so submissions should be filed within the fiscal year for which payment was made.

 

Choosing Wisely: Strategic Considerations

Selecting the correct FDA pathway is not merely a procedural step — it shapes your time-to-market, development budget, and regulatory risk profile.

Key strategic takeaways include:

• Start with classification: use FDA’s databases and, if unsure, the 513(g) request.
• Validate exemptions: always check section .9 limitations.
• Use predicates wisely: avoid referencing devices under recall.
• Engage early: pre-submission meetings build rapport with reviewers.
• Plan inspection readiness: quality documentation must meet 21 CFR 820 standards.

As Harris advised in the session, “The 510(k) process is the mechanism by which FDA puts you into their system to review you… but it’s your responsibility to know which path to take”.

 

Conclusion: A Strategic Approach to U.S. Market Entry

Bringing a medical device or in-vitro diagnostic to the U.S. market is a complex but navigable process when approached methodically.
Understanding how the FDA defines products, classifies risk, and determines submission routes enables companies to plan effectively, reduce delays, and demonstrate regulatory competence.

Whether your product follows the established 510(k) route, pioneers innovation via De Novo, or requires the rigour of a PMA, preparation, documentation, and early engagement are the keys to success.

Educo Life Sciences’ dedicated training courses help professionals master these steps — bridging regulatory understanding with practical application — so that teams can confidently achieve FDA clearance or approval and bring safe, effective medical technologies to patients worldwide.

Written by Educo Life Sciences Expert, Kathleen Harris

Kathleen Harris has over 30 years of experience in the Life Science and Pharmaceutical industries including as a regulator (USFDA). With degrees in Biology, Chemistry, and advanced degrees in Statistical Processes and Emerging Market Economics, she went to work for Bard Pharmaceuticals and Cook Biotech before working for the US Food and Drug Administration. Kathleen has since worked as Sr. Vice President of Regulatory and Quality for large multinational organizations. She started 2Harris consulting in 2014, offering comprehensive global regulatory strategies, ensuring seamless global product registration, and maintaining stringent quality compliance. Kathleen is a member of RAPS, ABHI, CLSI Standards Committee, AAMI, AvaMed and ACDI/VOCA.

This article was written using materials from the course, US FDA Regulatory Strategies for Medical Devices & IVDs