What Foreign IVD Manufacturers Need to Know Before Submitting to the FDA
Updated: 5 days ago
By David Petrich, Landrich Group Co-Founder and VP of Quality and Regulatory
Understanding Requirements to Access the U.S. Medical Device Market
The U.S. market for in vitro diagnostics and medical devices is the largest in the world. It accounts for roughly 46 percent of global medtech sales. For foreign manufacturers, it is also one of the most complex regulatory markets to enter. The U.S. Food and Drug Administration (FDA) is the national regulatory agency responsible for protecting public health and advancing healthcare innovations. The FDA device and IVD (In Vitro Diagnostics) requirements differ in important ways from other major regulatory systems, such as the CE marking in the European Union and the PMDA review process in Japan.
The FDA classifies IVDs and medical devices into three classes (Class I, II, III) based on risks to users and ties the premarket pathway directly to risk classification and statutory requirements. It does this through a structure and regulatory processes significantly different from other countries or jurisdictions.
This article provides an overview of key actions for foreign manufacturers who are preparing to enter the U.S. diagnostic market. If you are an IVD, CDx (Companion Diagnostics), or other medical device maker, this will prepare you with a plan for the next steps to formulate your U.S. market entry strategy.
Understanding U.S. Regulations and Taking the First Step
The first step in any effort to enter the U.S. medical device and diagnostic market is the selection of a U.S. Agent. The U.S. Agent requirement emerged as the FDA expanded oversight of imports in the 1990s and 2000s. Regulators needed a legally responsible contact within U.S. jurisdiction to facilitate registration, listing, medical device reporting, and foreign inspections, especially when direct communication with an overseas manufacturer was impractical. For more information on selecting a U.S. Agent, please check our article U.S. Agent Requirements for Foreign Medical Device Manufacturers: A Plain-English Guide.
Choosing the Appropriate Regulatory Pathway for Your Device
FDA categorizes IVDs and medical devices into three classes based on risk:
Class I: lowest risk, generally exempt from premarket review. This includes general laboratory and diagnostic tools, such as pipettes, non-sterile specimen collection containers, and general instruments such as microcentrifuges.
Class II: moderate risk, typically cleared through the 510(k) premarket notification process. This approval path requires demonstration of substantial equivalence to a legally marketed valid predicate device. 510(k) devices account for a large share of the U.S. diagnostics market. Examples include automated chemistry analyzers and immunoassay systems from EU and Japanese manufacturers. These are used in clinical laboratories for routine panels such as liver function tests, lipid profiles, and infectious disease serology. Other high-volume products in this category are point-of-care glucose meters and strips marketed by multinational firms with manufacturing sites outside the U.S.
Class III: highest risk, generally requires Premarket Approval (PMA) based on clinical evidence of safety and effectiveness. Devices in this category include IVDs whose results have a critical impact on treatment decisions or public health. Examples from foreign manufacturers in this category include certain companion diagnostic assays for targeted oncology therapies developed by EU‑ or Asia‑based companies. Other devices in the Class III category include high‑risk blood screening assays for HIV, hepatitis, and other transfusion‑transmitted infections manufactured outside the U.S. and supplied to American blood centers.
It is important to understand that for the FDA, risk class and premarket pathway are related but not identical concepts. Class I devices are often exempt from premarket review. Most Class II devices enter through the 510(k) process, which relies on equivalence to a predicate. Class III devices typically require Premarket Approval (PMA), which demands comprehensive modules for non-clinical data, manufacturing information, device labeling, and a clinical evidence package. Class III devices require pre-market approval and a FDA pre-approval inspection. Most Class I devices are exempt from pre-market approval, and Class II devices are cleared by the FDA if substantial equivalence to a legally marketed predicate device is demonstrated. Another viable route to market authorization in the U.S. is the De Novo pathway, taken from the Latin for “new” or “from the beginning.”
Unlike the EU IVDR and most Asian regulatory systems, the FDA created this DeNovo pathway solely to reclassify truly novel low‑ to moderate‑risk devices into Class I or II when no predicate exists, instead of defaulting them to Class III. This is a contrast to the IVDR approval process in the European Union, where novel IVDs still follow the same risk‑based classes (A–D) and notified‑body conformity assessment routes. It is also different than markets such as China, where they move through the standard Class II/III registration pathways, rather than a special “first of kind” route that recalibrates risk class.
Most IVD submissions to the FDA from foreign manufacturers are 510(k)s. The 510(k) process requires identifying a valid predicate device that is already legally marketed in the U.S. and has similar intended uses and equivalent technological characteristics. If no predicate exists, De Novo classification may be the appropriate pathway. An experienced U.S. Agent can assist foreign manufacturers to develop a U.S. regulatory strategy and determine whether to submit a product through the 510(k) or De Novo process as the most efficient and effective way to gain market authorization.
What the FDA Expects that is Different from Other Markets
In preparation for U.S. market entry, sometimes foreign manufacturers will understandably reference past experiences in Europe or other regulatory systems. This is an area for caution, since several FDA requirements have no direct equivalent in EU IVDR or other regulatory systems.
One example of this is Quality Management. The FDA requires a documented quality management system. This means that your company has a structured set of procedures, records, and responsibilities that describe how you design, manufacture, test, release, and monitor your devices. It also assumes that all of this is documented, controlled, and followed in your company’s daily operations.
Quality Management is governed through the FDA’s Quality System Regulation (21 CFR 820) and the new Quality Management System Regulation (QMSR). This includes documented processes for design control, purchasing, production, corrective and preventive actions, complaint handling, and management review. All of this must align with ISO 13485:2016 as a foundation. So, if your company already complies with ISO 13485, you are in a good position. However, you will still need to understand U.S.-specific requirements.
A prominent example of this is the Unique Device Identifier (UDI) classification process. This code in the U.S. has two components: a device identifier that lists the model/version of the device and a production identifier, which has information such as the lot, serial number, and expiration date. This system has evolved differently from comparable identification systems in Europe Union, Japan, and China, which are in different stages of maturity and phased implementation. Other examples include processes for complaint handling and additional traceability documentation for certain high-risk products such as implantables and life-support devices.
For manufacturers outside the U.S. who are familiar with the CE marking system in Europe, it is important to understand how this differs from the FDA process. In Europe, CE marking shows that a manufacturer has gone through a required conformity assessment to declare the product compliant for sale in that region. In a conformity marking system like CE, the company needs to provide evidence that it meets the rules and then labels the product. In the U.S. market, the FDA typically requires a company to go through a pre-market authorization system, asking for permission to sell the product. This means the company must use the correct regulatory pathway, such as 510(k), De Novo, or PMA, and then get explicit approval before marketing the device.
A recurring issue we see is when manufacturers with experience in Europe treat an IVDR Class C designation as proof that an IVD will be a “moderate risk” Class II device in the US through the standard 510(k) process. The FDA has classified some assays that are Class C under IVDR (such as certain genetic and infectious‑disease tests with major treatment implications) as Class III devices requiring PMA. This decision criterion was based on the potential impact of these devices on individual patient management and public health, regardless of the EU classification. When foreign manufacturers do not realize this until their initial interaction with FDA, they often face significant unplanned work to generate PMA‑level clinical evidence.
Clinical Evidence: Where Foreign Manufacturers Often Fall Short
For 510(k) submissions, FDA typically requires analytical and clinical performance data. For IVDs, this means studies demonstrating that the device performs as claimed in the U.S. intended use population. This is important to understand, as foreign manufacturers often have limited data from interactions with patients in the U.S. because their products are premarket.
“Intended use population” is the term used to define the group of patients and clinical settings for which your device is designed and described in the U.S. labeling. Examples of intended use population could be “adult patients being evaluated for acute chest pain in emergency departments” or “individuals 18 years and older being tested for chronic hepatitis C infection in hospital and reference laboratories.
This does not mean that clinical performance data generated outside the U.S. is invalid. It is often acceptable. The key qualifier is that the study population, specimen collection, and testing conditions must be representative of U.S. clinical practice. The FDA may also be willing to accept a specific percentage of U.S. versus foreign specimens and/or Real World Evidence (RWE) through its Q-Sub (or pre-submission) process, which may substantially reduce the cost and time for collecting and analyzing clinical evidence.
It is important to be as accurate as possible. If your U.S. product label claims that an assay is intended for use in symptomatic adults in emergency departments, studies conducted only in healthy volunteers at a single outpatient clinic are unlikely to reflect the real‑world population, specimen types, and pre‑analytical conditions FDA expects for that intended use.
A study conducted entirely in a specific regional population, or using specimen storage conditions that differ from U.S. laboratory standards, may not satisfy FDA's evidence requirements for a U.S. label.
Additionally, the FDA may require comparator data against a device that is the U.S. standard of care. Comparator data is the evidence from the reference test or standard you compare your device to in a clinical study. It shows whether your device performs as well as, better than, or differently from the accepted benchmarks. This may differ from the comparator used in the EU or other market submissions. In the EU, a legally marketed CE-marked device is typically used for performance evaluation studies, but that device may not be marketed or available in the U.S.
The leadership team at the Landrich Group has decades of experience conducting global trial work. We have found that one of the most consistent success factors has been designing global IVD studies with the U.S. market in mind from the first protocol draft.
In practice, this means a few things:
Selecting at least some sites in healthcare systems whose practice patterns, lab infrastructure, and patient mix closely resemble U.S. settings, even when the sponsor’s initial commercial focus is outside the U.S.
Aligning specimen collection, handling, and storage procedures to CLIA‑typical U.S. laboratory standards, so that bridging to an eventual FDA submission does not require repeating analytical or clinical performance work.
Confirming with FDA via pre‑submission the design of analytical and clinical studies and which U.S.‑marketed valid legal predicate, comparator assays, or ‘gold standard’ reference methods will be acceptable, then building those into the initial global protocol rather than running a separate, U.S.‑only comparator trial later.Across multiple 510(k) and De Novo programs, this approach has allowed sponsors to leverage a single, well‑designed global dataset to satisfy EU, U.S., and other major regulators, rather than maintaining separate evidence packages for each region.
The Value of the Pre-Submission Meeting
Before designing clinical studies intended to support a U.S. submission, the pre-submission process offers an excellent opportunity to check the suitability of your foreign clinical study designs and evidence for FDA approval.
FDA's pre-submission program allows manufacturers to ask specific questions about submission content, study design, and regulatory strategy before filing. FDA will provide written feedback on existing evidence, proposed study designs, intended use claims, and submission strategy. This significantly reduces the risk of filing a submission with requirement gaps. It is a key tool to budget required work to file an initial 510(k) or De Novo submission, avoiding costly re-runs and supplemental studies.
Under FDA’s Q‑Submission program, sponsors can request written feedback or a meeting (teleconference or face‑to‑face) to discuss questions related to the regulatory pathway. This includes clarifications regarding device description, intended use language, analytical and clinical study design, and the structure of the future marketing submission.
Conclusion
The U.S. regulatory pathway for IVD and medical device manufacturers does not forgive mistaken assumptions carried over from experience in other major markets in Europe and Asia.
For instance, a misunderstanding of the device classification criteria can turn a 510(k) submission into an unplanned PMA. Clinical data that satisfied competent authorities in the EU may not be sufficient for the FDA’s intended use population requirement. A U.S. Agent who acts as a mere messenger, without a deep understanding of the U.S. regulatory function, can delay or derail your submission. These are real risks that many foreign manufacturers have encountered in their first FDA encounter without the support of an experienced U.S.-based partner.
Studying the distinctive characteristics of U.S. medical device regulation with the support of a seasoned expert allows a foreign device maker to proceed with confidence to key steps in submission. The cost of correcting mid-submission problems, such as generating PMA-level clinical evidence, reconstructing study designs, and restarting pre-submission conversations, is always multiple times what it costs to get things in place for the first filing and interaction with the FDA.
CTA:
Landrich Group is based in the San Francisco Bay Area and supports IVD and device manufacturers across California and globally. If you are a non-U.S. IVD or CDx manufacturer planning a U.S. submission in the next 12–18 months, Landrich Group offers a focused U.S. Market Entry Readiness Review. We can assess your device classification, evaluate your existing clinical evidence against FDA's intended use population requirements, identify your pre-submission priorities, and deliver a structured roadmap for your first 12 months of FDA interactions. This way you have a solid plan in place before you commit resources to a submission strategy that may need to change. Contact us to schedule an initial consultation.
