The following steps can be taken to determine whether or not a new 510(k) is necessary for your device:

Does the change alter the operating principle of the IVD?

In most cases, a technology, engineering, performance, or material change that alters the operating principle of an IVD could significantly affect safety and effectiveness, in which case submission of a new 510(k) is required. Submission of a new 510(k) is not necessarily required for all changes in technology, engineering, performance, or materials for IVDs that alter the operating principle of an IVD. However, when such changes introduce novel technology that could have an impact on the ability of the device to extract, isolate, or detect the analyte(s) and could therefore affect the value assigned to the specimen, or could produce deviations in device performance that would result in modified reporting of performance in labeling, submission of a new 510(k) is likely required.

Examples of changes in technology, engineering, performance, or materials that likely alter the operating principle of the IVD and for which a new 510(k) is likely required include:

• changes from radioimmunoassays (RIA) to non-RIAs;
• changes in the antibody;
• ‍changes in detection reagents;
• ‍changes in critical reaction components; and
• ‍changes in conjugates.

Examples of changes in technology, engineering, performance, or materials that might alter the operating principle of the IVD include:

• changes from liquid to solid reagent;
• changes in calibration materials and quality control materials;
• ‍changes in substrates;
• ‍changes in specimen type;
• ‍changes in specimen processing; and
• ‍changes in incubation times and temperatures.

Examples of changes in technology, engineering, performance, or materials of an IVD which do not ordinarily affect the operating principle of the IVD include:

• changes to external packaging;
• ‍changes to use a new lot or batch for the same antibody or enzyme;
• ‍changes to a new vendor for the same reagent; and
• ‍changes in concentrations of packaged reagents provided the same diluted concentration was used in the assay.‍

Is the change identified in a device-specific final guidance or classification regulation?

When a device-specific final guidance identifies a change or modification that could significantly affect safety or effectiveness, submission of a new 510(k) is generally required. Additionally, in the case of some IVDs, FDA has established specific requirements (e.g. special controls) that are identified in the classification regulation. If a classification regulation identifies a change that could significantly affect safety or effectiveness, submission of a new 510(k) is required.

Does a risk-based assessment of the changed device identify any new risks or significantly modified existing risks?

Changes in the technology, engineering, design, or material used in an IVD can affect the performance, including the analytical or clinical performance, of the device. Further, certain changes in an IVD could also present new or significantly modified existing risks that could affect the overall risk profile of the IVD, apart from the performance (e.g. transmission of pathogenic diseases, biocompatibility or sterility issues).

For IVDs, a manufacturer’s risk-based assessment identifies new risks or significantly modified existing risks when the risk-based assessment:

• indicates that the performance of the modified test could significantly change from the previously cleared performance claims, or
• ‍identifies new risks or significantly modified existing risks, apart from performance.

If a change could affect the analytical performance of a device, particular attention should be paid to the effect on device performance around the clinical decision point(s) (i.e. cut-offs, cut-points). When new risks or significantly modified existing risks have been identified, in general, the change to the IVD could significantly affect safety or effectiveness of the device and submission of a new 510(k) is likely required. This includes a change that is clinically significant in terms of clinical decision making. Changes to components or accessories could, in some cases, significantly affect the safety or effectiveness of an IVD as a whole.

Changes in the human factors of a patient or user interface could, in some cases, significantly affect the safety or effectiveness of an IVD as a whole. Manufacturers should evaluate in their initial risk-based assessment whether a change in the human factors of a patient or user interface could significantly change the performance of the IVD or presents new risks or significantly modified existing risks. Manufacturers should consider the risk impact of changes in user workflow, such as providing new information to the user or modifying the manner in which information is presented, which may impact comprehension, or changing the layout of device controls, which may impact device use differently in different use scenarios.

Changes intended only to increase user or patient comfort when interacting with the device may be particularly difficult to evaluate. These changes will typically not present new risks or modified existing risks, but some changes made for the comfort of the user or patient could significantly affect safety or effectiveness. Manufacturers should evaluate the potential of changes to a user interface as to whether they could significantly affect safety or effectiveness.

Do design verification and/or validation activities produce any unexpected issues of safety or effectiveness?

Manufacturers should conduct an initial risk-based assessment of whether a change requires submission of a new 510(k); if the initial decision following the risk-based assessment is that submission of a new 510(k) is not required, the manufacturer should conduct design verification and/or validation activities to confirm the decision. Verification and validation activities should reevaluate the performance claims or performance specifications that were part of the original 510(k) clearance, as appropriate based on the manufacturer’s routine quality processes. Submission of a new 510(k) is likely not required where:

• ‍standard methods and performance criteria that have been established for evaluation of the specific device, as appropriate (e.g. protocols and criteria used to support the original 510(k) or a protocol established in the original 510(k) that described how anticipated changes would be evaluated), are used to verify and validate the modification;
• the results of verification and validation indicate that the performance is within the criteria;
• the performance of the modified IVD has not significantly changed from the previously cleared performance claims; and
• verification and validation do not reveal new risks or significantly modified existing risks apart from performance.

If all of these criteria are met, then the change is unlikely to significantly affect safety or effectiveness and manufacturers should proceed with the change making sure to document their assessment of whether submission of a new 510(k)is required. If any of these criteria are not met, it is likely that the change could significantly affect safety or effectiveness and that submission of a new 510(k) is required. If the results of routine verification and validation produce any unexpected issues or otherwise prove inadequate to verify and/or validate the change, it is likely that the change could significantly affect the IVD’s safety and effectiveness, and submission of a new 510(k) is likely required.

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