In-Vitro diagnostics (IVD) are products that are reagents, instruments, or systems that can detect diseases or other conditions and monitor a person’s overall health to help cure, treat, or prevent diseases.

The classification of an IVD determines the appropriate premarket process for approval. The FDA classifies IVD products into Class I, II, or III based on the associated risk.


Level of risk


Class I

Low to moderate risk

  • Complement reagent
  • Phosphorous test systems
  • E. coli serological reagent

Class II

Moderate to high risk

  • Immunological test system
  • Glucose test system
  • Coagulation instruments

Class III

High risk

  • Automated PAP smear readers
  • Nucleic acid amplification devices for tuberculosis


You can determine the classification by searching the FDA database using related search terms or identifying a similar device with the same intended use and technology. The 3-letter product code and 7- digit regulation number can be helpful for identification. If the classification cannot be determined, you can use the 513(g) process by the FDA.

Approval for Class I IVDs

Most of the Class I IVDs are exempted from the FDA requirements for premarket notification (510k) and Premarket Approval (PMA)

Approval for Class II IVDs

Most Class II IVDs are approved through the Premarket notification or 510(k) process. A 510(k) is a premarket submission made to the FDA to demonstrate that the diagnostic devices to be marketed are at least as safe and effective, Substantially Equivalent (SE), to a legally marketed one. For IVDs, the review of a 510(k) includes an evaluation of the analytical performance characteristics of the new device compared to the predicate, including:

  • The bias or inaccuracy of the new device
  • The imprecision of the new device
  • The analytical specificity and sensitivity

A step-by-step process for preparing and submitting a 510(k) application is carried out by the manufacturer, and the FDA user fee is paid. If the device is deemed cleared in the 510(k)-review process, the submitter receives an SE letter, and the device will be listed in the 510(k) FDA database. If a non-high-risk IVD with no predicate is shown, it may be reviewed and placed under a Class I or Class II under a De-Novo submission classification.

Approval for Class III IVDs

Most Class III devices are subject to the Pre-Market Approval (PMA) process, wherein the diagnostic technology to be marketed cannot be considered substantially equivalent to the existing technology. A PMA application is submitted per FDA guidance, and a user fee is paid. Upon approval, FDA issues a PMA approval letter and posts it online.

The foreign manufacturer must appoint a US agent representative as a local point of contact with the US FDA, irrespective of the risk class of the device.

Labeling Requirements

IVDs have additional labeling requirements under 21 CFR 809, Subpart B, In Vitro Diagnostic Products for Human Use. Before a manufacturer obtains marketing authorization for an IVD product, they must label it according to the regulations.

After the required clearance, grant, or approval of the IVD, the manufacturer must register the establishment and list the IVD in FURLS system. The manufacturer must pay an annual fee to maintain its establishment registration.

Approval for Companion Diagnostics (CDx)

An IVD companion diagnostic device provides information essential for the safe and effective use of a particular therapeutic product. A companion diagnostic, or CDx, informs the use of personalized treatment options for advanced cancer patients by identifying FDA-approved treatment options that may be appropriate based on the unique drivers of their cancer. The US FDA follows a risk-based approach for the approval of companion diagnostics. The level of risk will determine if the IVD companion diagnostic requires a PMA or a 510(k).

The US FDA reviews each CDx device within the context of the corresponding therapeutic product. The CDx manufacturers can opt for any of the following submission and approval scenarios:

  • The IVD is already approved and legally marketed, and the IVD manufacturer intends to add a new indication for use as a CDx with a drug or biological product. The manufacturer must submit an additional premarket submission for the new intended use.
  • Both the CDx and drug or biological products are novel, and CDx is essential for the safe and effective use of the product. The CDx and the therapeutic product should be developed and approved simultaneously.
  • If US FDA determines that the CDx is essential for the safe and effective use of a novel therapeutic product, US FDA generally will not approve if the CDx is not approved or cleared for that indication.
  • In case of a new biological product intended to treat severe/life-threatening conditions or already approved therapeutic products, US FDA may approve the biological product without approval or clearance of companion diagnostic.

It is recommended that sponsors time their clinical developments and premarket submissions as they can initiate early consultations with US FDA to determine the appropriate Regulatory pathway. The FDA intends to issue approvals for the CDx and the therapeutic product simultaneously.

In case of more queries and assistance for approvals of your IVD products and companion diagnostics in the U.S., feel free to schedule a call with our Regulatory experts.

Stay informed, and stay compliant!


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