In Vitro Diagnostic Devices (IVDs), FDA Classification and Regulatory Pathways Explained

In vitro diagnostic devices, commonly referred to as IVDs, play a critical role in modern healthcare by enabling the detection, diagnosis and monitoring of disease. These products inform clinical decision making across a wide range of settings, from central laboratories to point of care environments and, increasingly, the home. In the United States, IVDs are regulated as medical devices under the Federal Food, Drug and Cosmetic Act and are subject to a structured, risk based regulatory framework administered by the FDA. For manufacturers, understanding how IVDs are defined, classified and reviewed is essential for selecting the correct regulatory pathway, generating appropriate evidence and maintaining long term compliance.

What Is an In Vitro Diagnostic Device

An in vitro diagnostic device is a reagent, instrument or system intended for use in the diagnosis of disease or other conditions, or to determine the state of health, to cure, mitigate, treat or prevent disease or its sequelae. IVDs are intended for use in the collection, preparation and examination of specimens taken from the human body, such as blood, urine, tissue or saliva. Under section 201(h)(1) of the Act, these products meet the definition of a medical device and are therefore subject to FDA premarket and post-market controls. In addition to FDA oversight, most IVDs are also categorised under the Clinical Laboratory Improvement Amendments of 1988, known as CLIA, which governs laboratory testing complexity and operational requirements.

Why Classification Matters for IVDs

The classification of an IVD determines the regulatory controls that apply throughout the product lifecycle. Classification affects the premarket pathway, the type and volume of data required to support marketing authorisation, labelling obligations, quality system requirements and post market responsibilities. An IVD may be subject only to general controls, or it may also be subject to special controls or premarket approval, depending on its risk profile. Selecting the correct classification early in development is therefore a critical strategic step, as it directly influences development timelines, cost and regulatory risk.

How the FDA Classifies IVDs

IVDs are classified according to risk, considering the intended use of the test and the potential consequences of incorrect results. FDA broadly categorises devices as low, moderate, or high risk. For IVDs, risk is driven not only by the underlying technology but also by how the test results are used clinically and the impact of false positive or false negative results.

The FDA assigns devices to generic device types defined in the Code of Federal Regulations, primarily within 21 CFR Parts 862, 864 and 866. Each generic device type has an associated classification and sets of regulatory controls. Once a generic type exists, individual devices that fall within that definition are regulated in the same way. If a device does not fit within an existing classification, it is considered novel and initially defaults to Class III, unless the manufacturer successfully requests De Novo classification to establish a new Class I or Class II device type.

Key Determinants of IVD Classification

Before discussing the specific classes, it is important to understand the factors that drive classification decisions.

The intended use and indications for use define what the test is intended to do, such as diagnosing disease, screening asymptomatic populations, monitoring disease progression or predicting risk. The target condition and patient population also influence risk, for example whether the test is used for life threatening conditions or routine wellness monitoring.

The test method and technology are also relevant, including whether the test uses PCR, immunoassay, sequencing or other analytical techniques, the type of specimen analysed and whether results are qualitative or quantitative.

Finally, the context of use plays a major role. Tests intended for high complexity laboratories may present different risks compared to point of care or at home tests, where user training and environmental controls are more limited.

IVD Classification by Risk Class

IVDs are grouped into three regulatory classes.

Class I IVDs are generally low risk and are subject only to general controls. These include requirements for registration and listing, labelling, quality system compliance and adverse event reporting. Most Class I IVDs are exempt from premarket notification, although not all are. Approximately half of all IVDs listed with the FDA fall into Class I.

Class II IVDs are typically moderate risk and are subject to general controls plus special controls. Special controls are device type specific and may include performance standards, specific labelling requirements, validation requirements or post-market surveillance obligations. Most Class II IVDs require a 510(k) premarket notification demonstrating substantial equivalence to a legally marketed predicate device, although some Class II devices are exempt. Around 45 percent of FDA listed IVDs are Class II.

Class III IVDs are high-risk devices that support or sustain human life, are critical to preventing serious impairment of health or pose an unreasonable risk if they fail. These devices are subject to general controls and premarket approval, which is the most stringent level of FDA review. Only a small proportion of IVDs, approximately five percent, are Class III.

General and Special Controls

General controls apply to all medical devices, including IVDs, unless specifically exempted. These controls include labelling requirements, Medical Device Reporting (MDR), establishment registration, device listing and quality system requirements.

Special controls apply to certain Class II device types and are designed to provide reasonable assurance of safety and effectiveness. These may include performance standards, post-market surveillance requirements, patient registries, special labelling provisions, specific premarket data requirements or FDA guidance documents. Compliance with special controls is a prerequisite for clearance of a Class II IVD.

Recent Developments and Reclassification Trends

In January 2024, the FDA announced its intention to initiate the re-classification process for many IVDs currently regulated as Class III into Class II. This effort focuses particularly on infectious disease tests and companion diagnostic IVDs. The objective is to reduce regulatory burden by enabling use of the 510(k) pathway rather than PMA, while maintaining appropriate controls.

Although re-classified devices would still undergo premarket review and be subject to general and special controls, the shift could significantly reduce development cost and time to market. This initiative reflects a broader FDA trend toward risk-based regulation and increased reliance on special controls where appropriate.

Practical Steps to Determine IVD Classification

Manufacturers developing or evaluating an IVD should take a structured approach to classification.

The first step is to define the intended use and indications for use precisely, including the analyte, specimen type, target population, clinical context and how results will be used.

Next, the FDA Product Classification Database should be searched to identify whether a matching generic device type exists. If found, the database provides the regulation number, classification, product code and whether premarket notification is required or exempt.

If no matching classification exists, the device is novel and the manufacturer should consider whether a De Novo request is appropriate or whether PMA is likely required based on risk.

Once classification is identified, the applicable general and special controls or PMA requirements should be reviewed in detail to inform evidence generation and development planning.

Subsets of IVDs

Certain categories of IVD related products warrant specific consideration.

General purpose reagents are chemical reagents with general laboratory applications that are not intended for a specific diagnostic use. These products are typically classified as Class I and are usually exempt from premarket notification, provided they comply with general controls and labelling requirements.

Analyte specific reagents are antibodies, nucleic acid sequences and similar reagents that bind specifically to substances in a specimen and are intended for diagnostic applications. ASRs are regulated under specific provisions and have defined labelling and distribution requirements.

Pre Submissions for IVDs

The FDA Pre Submission (Pre-Sub) process, part of the Q Submission Program, provides an opportunity for manufacturers to obtain non-binding feedback from the FDA before submitting a marketing application. Pre-Subs are particularly useful for IVDs involving new technology, novel intended uses, unclear regulatory pathways, complex study designs or multiplex assays.

Benefits include:

• Early clarification of regulatory expectations
• Reduced risk of unnecessary studies
• Increased FDA familiarity with the device prior to formal review. 

Although voluntary, Pre Submissions are widely used and can significantly improve the efficiency of subsequent submissions.

Labelling Requirements for IVDs

IVDs are subject to additional labelling requirements under 21 CFR 809 Subpart B. Before marketing, manufacturers must ensure that labelling complies with these provisions, which address intended use statements, limitations, warnings, performance characteristics and instructions for use. Labelling must be consistent with the cleared or approved indications and supported by the submitted evidence.

LFH supports IVD manufacturers in navigating FDA classification, premarket pathways and post-market compliance. Our regulatory specialists help organisations define intended use, select appropriate pathways and build proportionate evidence strategies to support efficient and compliant market access in the United States.

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