Approval Letter Other 209988 (Jan 1, 2023)

The sponsor made significant changes to the design of the to-be-marketed device during the review cycle without the FDA’s prior knowledge. This raises questions about the safety and efficacy and the relevance of previously submitted documentation. The FDA cannot determine if the original submission supports the safety and effectiveness of the current design.

Recommended response: Resubmit with the finalized to-be-marketed device and all supporting documentation. Clearly state any testing performed on previous versions and justify its relevance.

Significant documentation for the device constituent relies on a Master Access File (MAF). There are outstanding deficiencies communicated separately to the MAF Holder.

Recommended response: Work with the MAF Holder to resolve all identified deficiencies. Resubmit the NDA only after all deficiencies are resolved and adequate documentation is present in the MAF.

Differences exist between the biocompatibility test article and the final finished product. Particulates testing per USP <788> method 1 light obscuration method is required on the final finished device to ensure particulate matters are within an acceptable range.

Recommended response: Provide particulates testing per USP <788> method 1 light obscuration method on the final finished device. Address the differences between the test article and the final product.

Cited: USP <788>

Particulate testing was stated to be conducted per USP <788>, but it's unclear if Method 1 (Light Obscuration) or Method 2 (Microscopic) was used. For infusion devices, Method 1 is recommended.

Recommended response: Clarify which USP <788> method was used. If Method 2 was used, provide new testing per USP <788> method 1 light obscuration method.

Cited: USP <788>

Inconsistent information regarding the method used to evaluate cytotoxicity for the adhesive patch (ISO vs. ISO Direct Contact Method). Justification for the chosen method is required.

Recommended response: Clarify which method was used to evaluate the cytotoxicity endpoint for the adhesive patch and provide justification for this method.

Cited: ISO

The sample preparation for leachable testing used a specific method, but it is unclear if the extraction occurred under clinically relevant conditions.

Recommended response: Discuss and clarify if the sample preparation and test extract method is clinically relevant. Alternatively, provide new testing under clinically relevant conditions.

In GC/MS direct injection results for leachables, spike recoveries were reported, but it's unclear how the sponsor ensures detection of semi-volatile and volatile compounds.

Recommended response: Provide a rationale justifying that the methods are appropriate for detecting semi-volatile and volatile compounds or provide new testing using appropriate methods.

Labeling does not contain adequate electrical safety and electromagnetic compatibility information as recommended by IEC 60601-1 series. Specific issues include insufficient EMC warning text, missing essential performance information, and missing battery specifications.

Recommended response: Revise labeling to include adequate EMC warnings (e.g., specific distance for RF communications equipment), essential performance information, and battery specifications (type, rated voltage, power) as recommended by IEC 60601-1 series.

Cited: IEC 60601-1-2:2014, IEC 60601-1

The sponsor failed to update labeling as previously requested and it lacks critical warnings and information. Specific missing items include electrical safety/EMC symbols, software version, accuracy factors, residual volume, warnings for CT/ultrasound/X-ray environments, and adherence to home-use and infusion pump guidance.

Recommended response: Provide all originally requested labeling updates. Ensure labeling contains all specified warnings and information, including electrical safety/EMC symbols, software version, accuracy factors, residual volume, and warnings for various environments. Ensure compliance with referenced FDA guidance documents.

The sponsor stated the infusor was validated for clinic or home settings but provided insufficient evidence, and the response to IR #2a remains incomplete.

Recommended response: Update the device's Instructions for Use and provide sufficient evidence to support validation for home use.

The human factors/usability use-related risk analysis does not assess risks for patients with specific exclusion criteria (e.g., chronic skin conditions, allergies to adhesives, recent medication use, skin conditions on abdomen). The proposed Instructions for Use (IFU) also lacks adequate information beyond a general statement.

Recommended response: Submit an updated use-related risk analysis assessing risks for patients with the listed characteristics. If critical tasks are identified, update IFU with risk mitigations (contraindications, warnings) and submit supplemental human factors validation study data or justification. Add appropriate contraindications to the Prescribing Information (PI) or justify omission.

The human factors (HF) study report was included with the resubmission, but a subsequent Device Improvement Report indicates the device was modified after the HF study. The FDA expects the HF validation study to be conducted with the to-be-marketed device.

Recommended response: Conduct a new human factors validation study with the finalized, to-be-marketed device.