1037-00002 · Client 1037 · Strategy & Analysis

icgm-special-controls-memo.docx DOCUMENT Finance & Banking

33 / 40 ← → ✕

MEMORANDUM

PRIVILEGED AND CONFIDENTIAL — ATTORNEY-CLIENT COMMUNICATION

From: Calderwood & Harkness LLP

Miriam Calloway, Partner, Healthcare & Life Sciences — Responsible Partner Amy Whitfield, Associate, Healthcare & Life Sciences — Lead Associate Sean Morrissey, Associate, Healthcare & Life Sciences — Working Associate

To: Dr. Niamh Tierney, Vice President of Regulatory Affairs, Solstice Biomedical Devices Ltd. Marcus Hale, Vice President of U.S. Operations, Solstice Biomedical Inc.

CC: Dr. Eoin Gallagher, Chief Executive Officer, Solstice Biomedical Devices Ltd. Dr. Aisling Burke, Chief Technology Officer, Solstice Biomedical Devices Ltd. Joel Strauss, Billing Partner, Calderwood & Harkness LLP

Date: May 2, 2025

Re: Analysis of Integrated Continuous Glucose Monitoring (iCGM) Classification and Applicable Special Controls — Solstice Lumina™ CGM System

Engagement Reference No.: 1037-00002

Right-click to update Table of Contents

I. Executive Summary

The purpose of this memorandum is to provide Solstice Biomedical Devices Ltd. and Solstice Biomedical Inc. (collectively, "Solstice") with a comprehensive legal and regulatory analysis of whether the Solstice Lumina™ CGM System — comprising the Lumina C14 implantable sensor and the Lumina R7 wearable reader/transmitter — qualifies for classification as an integrated continuous glucose monitoring ("iCGM") device under the U.S. Food and Drug Administration's ("FDA's") De Novo classification order DEN170088 and the applicable special controls established thereunder.

Based on our review of the applicable regulations, FDA guidance documents, the De Novo classification framework, the technical specifications of the Lumina CGM System, and the regulatory submissions of comparable predicate devices, we conclude that the Lumina CGM System is well-positioned to pursue iCGM classification, provided it meets the stringent analytical performance criteria established for iCGM devices. The key performance benchmarks include: (i) an overall Mean Absolute Relative Difference ("MARD") of ≤ 9.0%; (ii) ≥ 99% of paired CGM-reference data points falling within Zones A and B of the Clarke/Consensus Error Grid; and (iii) satisfaction of all other applicable iCGM special controls relating to alarm/alert performance, software and cybersecurity documentation, interoperability, labeling, and quality system requirements.

The strategic advantages of iCGM classification for Solstice's U.S. market entry are substantial. Under the iCGM framework, the Lumina CGM System would be eligible for interoperability with secondary display devices and automated insulin dosing ("AID") systems without requiring Solstice to obtain separate 510(k) clearances for each integrated device configuration. This would materially accelerate Solstice's ability to participate in the growing diabetes management ecosystem in the United States, enhance competitive positioning relative to existing CGM products, and potentially facilitate favorable reimbursement pathways given payer preference for iCGM-classified devices.

This memorandum is being provided in advance of the Pre-Submission ("Q-Sub" or "Pre-Sub") meeting with FDA's Center for Devices and Radiological Health ("CDRH"), Office of Health Technology 2 ("OHT2"), Division of Chemistry and Toxicology Devices, which is currently targeted for August 14, 2025. The analysis herein is intended to inform the questions that Solstice will present to FDA regarding the iCGM classification pathway and to frame the regulatory strategy for the Lumina system's 510(k) submission. We recommend that Solstice include specific questions regarding iCGM classification in the Pre-Sub meeting package, which is targeted for submission to FDA by June 16, 2025, consistent with the meeting request anticipated to be submitted on June 2, 2025.

The remainder of this memorandum is organized as follows: Section II provides background on the Lumina CGM System, Solstice's regulatory history, and the identified predicate devices. Section III describes the regulatory framework for iCGM classification, including the De Novo classification order and applicable FDA guidance. Section IV provides a detailed analysis of each category of iCGM special controls and their application to the Lumina system. Section V compares the iCGM classification pathway with the standard 510(k) CGM pathway. Section VI presents a gap analysis of the Lumina system's readiness for iCGM classification. Sections VII through XI address interoperability implications, freedom-to-operate considerations, recommended strategy and Pre-Sub meeting questions, timeline implications, and estimated cost implications. Section XII offers our conclusions.

II. Background

A. The Solstice Lumina™ CGM System

The Solstice Lumina™ CGM System is a continuous glucose monitoring system designed for real-time measurement of glucose concentrations in persons aged eighteen (18) years and older who have been diagnosed with Type 1 or Type 2 diabetes mellitus. The system comprises two device variants and associated software components, which together constitute a single system intended for submission to FDA.

Device Variant 1: Lumina C14 Sensor. The Lumina C14 is a subcutaneously implantable continuous glucose monitoring sensor with a maximum intended wear duration of fourteen (14) days (336 hours). The C14 sensor employs a fourth-generation enzymatic electrochemical biosensor utilizing Solstice's proprietary platinum-iridium electrode coating technology, designated "PtIr-4G." The PtIr-4G technology represents an advancement over prior-generation platinum electrode coatings and is designed to enhance sensor linearity, reduce signal drift over the sensor's functional life, and improve interference rejection characteristics. The C14 sensor communicates wirelessly with the Lumina R7 reader/transmitter via Bluetooth Low Energy ("BLE") 5.2 data transmission protocol.

Device Variant 2: Lumina R7 Reader/Transmitter. The Lumina R7 is a wearable reader/transmitter device designed to be worn on the user's upper arm. The R7 receives BLE data transmissions from the C14 sensor and provides the user with real-time glucose values, directional trend arrows indicating the rate of glucose change, and eight (8)-hour trend graphs. The R7 includes configurable hypoglycemia and hyperglycemia alerts, which can be set by the user to activate at user-defined glucose thresholds. The R7 communicates with the Solstice Lumina™ mobile application (available on iOS and Android platforms) via BLE, enabling users to view their glucose data on a smartphone or tablet device.

Key System Specifications. The system's key technical specifications, as documented in Solstice's design history file and communicated to this firm, are as follows:

• Measurement range: 40–400 mg/dL

• Warm-up time: ≤ 60 minutes from sensor insertion to first glucose reading

• Alert latency: ≤ 5 minutes from sensor glucose reading to user notification on the R7 reader or Lumina Mobile App

• Firmware/Software versions: Lumina Firmware v3.4.2 (C14 sensor), Lumina Reader OS v2.1.0 (R7 reader), LuminaPredict Algorithm v2.1 (proprietary glucose prediction algorithm), Lumina Mobile App v1.0.3

• Anticipated product code: QKQ (Electrode, Glucose, Subcutaneous)

• Anticipated regulation number: 21 C.F.R. § 862.1355 (Glucose test system)

• Anticipated device class: Class II

• Submission type planned: Traditional 510(k) covering both the C14 sensor and the R7 reader/transmitter as a single system

B. Solstice's Regulatory History and EU Market Status

Solstice has prior experience with FDA regulatory submissions. Solstice previously obtained 510(k) clearance for the GlucoStrip RX-200 Test Strip Reader, under 510(k) No. K192847, which was cleared by FDA on November 14, 2019. The GlucoStrip RX-200 was classified under product code NBW as a Class II device. This prior clearance is cited herein solely for the purpose of establishing Solstice's corporate pedigree and prior interaction with FDA's device review program; the GlucoStrip RX-200 is not being cited as a predicate device for the Lumina CGM System, as it is a fundamentally different device type (a blood glucose test strip reader rather than a continuous glucose monitor).

The Lumina CGM System has been commercially available in the European Union since September 2024. Solstice obtained EU Medical Device Regulation ("MDR") CE certification for the Lumina CGM System, issued by Meridian Conformity Assessment GmbH (Notified Body No. 0483), under Certificate No. MCA-2024-07319, dated September 12, 2024. Solstice additionally holds ISO 13485:2016 quality management system certification, also certified by Meridian Conformity Assessment GmbH. The EU commercial experience with the Lumina system provides Solstice with real-world performance data and post-market surveillance information that may be supportive — though not dispositive — in the U.S. regulatory submission context. As discussed further in Section IV below, FDA will require U.S.-based clinical data from the planned LUMINA-US pivotal study to support iCGM classification; EU data alone will not be sufficient.

The Lumina CGM System does not have any existing FDA clearance or approval in the United States. The 510(k) submission contemplated herein will be Solstice's initial U.S. market authorization application for the Lumina system.

C. Predicate Devices

Calderwood & Harkness, in coordination with Pinnacle Regulatory Consulting Group LLC ("Pinnacle Regulatory"), has identified the following predicate devices for the Lumina CGM System's 510(k) submission:

Primary Predicate Device: NovaSense GlucoTrack NX-500 CGM System. The NovaSense GlucoTrack NX-500 CGM System received 510(k) clearance under 510(k) No. K211034, cleared on June 18, 2022. The NX-500 is classified under product code QKQ as a Class II device. The NX-500 is an enzymatic electrochemical CGM sensor with a ten (10)-day sensor wear duration and BLE wireless data transmission to a dedicated reader device. The NX-500 provides a strong technological basis for substantial equivalence comparison with the Lumina C14/R7 system, given the shared fundamental technology (enzymatic electrochemical sensing) and intended use population.

Secondary Predicate Device (Reference Device): NovaSense GlucoTrack NX-700 CGM System. The NovaSense GlucoTrack NX-700 CGM System received 510(k) clearance under 510(k) No. K230489, cleared on March 7, 2024. The NX-700 is also classified under product code QKQ as a Class II device. The NX-700 features an extended fourteen (14)-day sensor wear duration and enhanced BLE 5.0 data transmission, along with an updated glucose prediction algorithm. The NX-700 is being cited as a secondary predicate device, particularly to support the Lumina system's fourteen-day wear duration claim and updated wireless transmission capabilities.

Both predicate devices are manufactured by NovaSense Medical Technologies Inc. ("NovaSense"), a Delaware corporation (File No. 5429876), headquartered at 4800 Innovation Parkway, San Diego, California 92121. NovaSense's Chief Executive Officer is David Reinhardt, and its Vice President of Regulatory Affairs is Dr. Karen Nishimura. NovaSense reported fiscal year 2024 revenue of approximately $1.24 billion, making it a significant competitor in the continuous glucose monitoring market. The regulatory status of the NovaSense predicate devices with respect to iCGM classification is a material consideration for Solstice's iCGM strategy and is analyzed further in Section V below.

III. Regulatory Framework for iCGM Classification

A. Historical Context: De Novo Classification Order DEN170088

The iCGM classification was established by FDA through a De Novo classification request, designated DEN170088, which was granted in 2018. The De Novo pathway, codified at 21 U.S.C. § 360c(f)(2) and 21 C.F.R. Part 860, Subpart D, permits FDA to classify novel medical devices of low to moderate risk for which there is no legally marketed predicate device. When FDA grants a De Novo classification request, it simultaneously creates a new regulatory classification that subsequent devices of the same type may reference through the traditional 510(k) premarket notification pathway.

The creation of the iCGM classification represented a significant regulatory innovation in the diabetes device space. Prior to DEN170088, CGM devices were classified as standard Class II medical devices under 21 C.F.R. § 862.1355, and any integration between a CGM system and a secondary device (such as an automated insulin dosing system or an insulin pump) required the integrated system to undergo a combined premarket review. This approach was inefficient, costly, and inhibited innovation in the emerging field of interoperable diabetes management systems.

Through DEN170088, FDA established the iCGM as a distinct regulatory classification within the broader category of glucose test systems. The iCGM classification was specifically designed to facilitate interoperability between CGM systems and secondary digitally connected devices within an integrated diabetes management ecosystem. Under this framework, an iCGM device that meets the specified special controls can be used with secondary devices — including AID systems, secondary display devices, and insulin pumps — without requiring each integrated configuration to undergo a separate FDA review. This "plug-and-play" regulatory model was intended to accelerate the development and commercialization of interoperable diabetes management systems while maintaining appropriate safeguards through stringent performance criteria.

iCGM devices are classified as Class II medical devices under 21 C.F.R. § 862.1355, with special controls that go beyond those applicable to standard (non-integrated) CGM devices. The special controls establish the performance, design, clinical evidence, labeling, software, cybersecurity, and quality system requirements that an iCGM device must satisfy in order to provide reasonable assurance of safety and effectiveness.

The critical distinction between iCGM and non-integrated CGM devices is that iCGM devices are specifically intended to be compatible with other digitally connected medical devices, and must meet specific accuracy and reliability criteria set forth in the special controls that ensure the glucose data output is sufficiently accurate and reliable for use by secondary devices in automated therapeutic decision-making. A non-integrated CGM device, by contrast, is intended for standalone use and does not carry interoperability labeling or the attendant performance obligations.

B. Applicable Regulation: 21 C.F.R. § 862.1355

The regulation number anticipated for the Solstice Lumina™ CGM System — 21 C.F.R. § 862.1355, titled "Glucose test system" — is the same regulation that governs iCGM devices. This regulation covers devices intended to measure glucose quantitatively in blood, interstitial fluid, or other body fluids. Under the current regulatory framework, both standard CGM devices and iCGM devices are classified under § 862.1355, with the distinction between the two classifications determined by the applicable special controls and the device's intended use with respect to interoperability.

FDA issued a reclassification order effective March 2024 that updated the classification framework for CGM devices under this regulation. The reclassification order consolidated several CGM device types under 21 C.F.R. § 862.1355 and modified the applicable special controls to reflect current technological capabilities and clinical evidence standards. The March 2024 reclassification order is relevant to Solstice's iCGM strategy because it updated certain performance expectations and documentation requirements that will apply to the Lumina CGM System's 510(k) submission. Specifically, the reclassification order clarified the relationship between standard CGM and iCGM special controls and confirmed that product code QKQ applies to subcutaneous glucose electrode sensors used in continuous monitoring systems, irrespective of whether the device seeks iCGM or standard CGM classification.

Product code QKQ, which is the product code anticipated for the Lumina CGM System, encompasses electrode-based glucose sensors designed for subcutaneous implantation and continuous glucose monitoring. This product code covers both the sensor component and the associated reader/transmitter when submitted as a system, consistent with Solstice's planned submission approach.

C. FDA Guidance: "Integrated Continuous Glucose Monitoring Systems" (September 2023)

In September 2023, FDA published a guidance document titled "Integrated Continuous Glucose Monitoring Systems," which provides detailed recommendations regarding the performance criteria, labeling requirements, and clinical evidence expectations for devices seeking iCGM classification. This guidance document is the most current and comprehensive statement of FDA's expectations for iCGM devices and will be a central reference point in both the Pre-Sub meeting discussion and the eventual 510(k) submission.

The September 2023 guidance document addresses several critical areas for iCGM classification. First, it describes the analytical accuracy performance criteria that iCGM devices must meet, including the overall MARD threshold, point accuracy requirements, and glucose range-specific performance benchmarks. Second, the guidance establishes alarm performance criteria, addressing the sensitivity, specificity, and latency of hypoglycemia and hyperglycemia alerts. Third, the guidance describes the data output requirements for interoperability, specifying the format and content of glucose data that an iCGM must provide to secondary devices. Fourth, the guidance outlines cybersecurity expectations for iCGM devices, reflecting the heightened security risks associated with devices that transmit glucose data to automated therapeutic systems.

It is important to note that, as with all FDA guidance documents, the September 2023 guidance is not legally binding on either FDA or device manufacturers. The guidance states that it "represents the current thinking of the Food and Drug Administration" and that "an alternative approach may be used if such approach satisfies the requirements of the applicable statutes and regulations." Notwithstanding this caveat, the September 2023 guidance represents FDA's most authoritative statement of its current expectations for iCGM devices, and we strongly recommend that Solstice treat the guidance's recommendations as the operative performance benchmarks for purposes of iCGM classification. Deviation from the guidance's recommendations without strong scientific justification would likely result in additional information requests during FDA review and potential delays in the 510(k) clearance timeline.

The guidance document will be a key input for the Pre-Sub meeting discussion, and we recommend that the Pre-Sub meeting package specifically reference the guidance and seek FDA's feedback on Solstice's proposed approach to meeting the guidance's recommendations.

IV. Special Controls Applicable to iCGM Devices

This Section provides a detailed analysis of each category of special controls applicable to iCGM devices and their application to the Solstice Lumina™ CGM System. The special controls established under De Novo classification order DEN170088, as updated by the March 2024 reclassification order, encompass the following categories: (A) analytical performance criteria; (B) design verification and validation requirements; (C) clinical evidence requirements; (D) software and cybersecurity special controls; (E) labeling and interoperability requirements; and (F) quality system requirements.

A. Analytical Performance Criteria

1. MARD (Mean Absolute Relative Difference) Requirement

The Mean Absolute Relative Difference, commonly referred to as MARD, is the primary accuracy metric used to evaluate CGM device performance. MARD quantifies the average deviation between CGM glucose readings and paired reference glucose measurements (typically obtained via YSI laboratory-grade glucose analyzer), expressed as a percentage of the reference value. A lower MARD value indicates higher CGM accuracy relative to the reference standard.

The iCGM special controls require demonstration of a MARD that is consistent with the safe and effective use of the device in conjunction with secondary digitally connected devices, including AID systems. FDA's September 2023 guidance document recommends an overall MARD of ≤ 9.0% as the benchmark for iCGM classification. This threshold reflects FDA's assessment that CGM data used to drive automated insulin dosing decisions must meet a higher accuracy standard than CGM data used solely for informational purposes.

Solstice has established a MARD target of ≤ 9.0% overall for the Lumina CGM System, which is aligned with the iCGM requirement. Achieving this target will be critical to iCGM classification, and Solstice should be aware that the MARD target is not simply a mean performance goal but must be demonstrated with statistical rigor across the full measurement range and across the full sensor wear duration.

Specifically, MARD must be demonstrated across the full measurement range of the Lumina system (40–400 mg/dL), and FDA is expected to require stratification of MARD performance by glycemic range. The three standard glycemic ranges for MARD stratification are:

• Hypoglycemic range: < 70 mg/dL

• Euglycemic range: 70–180 mg/dL

• Hyperglycemic range: > 180 mg/dL

Accurate performance in the hypoglycemic range is of particular importance for iCGM devices, because inaccurate glucose readings in the low glucose range can lead to inappropriate insulin dosing by AID systems, with potentially severe clinical consequences including insulin-induced hypoglycemia. FDA may establish more stringent MARD sub-thresholds for the hypoglycemic range, and Solstice should anticipate that FDA will scrutinize hypoglycemic-range accuracy data with particular rigor.

In addition, MARD performance must be maintained across the full fourteen (14)-day sensor wear duration (336 hours) of the Lumina C14 sensor. FDA is expected to require analysis of MARD performance as a function of sensor age, including degradation analysis demonstrating that sensor accuracy does not deteriorate below the iCGM threshold over the sensor's functional life. This degradation analysis should account for known phenomena such as membrane biofouling, enzyme activity decay, and electrode drift, all of which can affect sensor accuracy over extended wear periods. Solstice's PtIr-4G electrode coating technology is designed to mitigate certain of these degradation mechanisms, and Solstice should be prepared to present data demonstrating the stability of sensor performance over the full fourteen-day wear period.

2. Consensus Error Grid / Point Accuracy

In addition to the overall MARD requirement, the iCGM special controls require that a device demonstrate high point accuracy as measured by the Clarke Error Grid Analysis or the Consensus Error Grid Analysis. Specifically, the iCGM special controls require that ≥ 99% of paired CGM-reference data points fall within Zones A and B of the Clarke or Consensus Error Grid. Zone A represents glucose values within 20% of the reference value (or within 20 mg/dL for reference values below 70 mg/dL) — clinically accurate readings that would lead to correct treatment decisions. Zone B represents glucose values that would lead to benign treatment decisions or no treatment. Points falling outside Zones A and B (i.e., in Zones C, D, or E) represent clinically significant errors that could lead to unnecessary treatment, failure to detect problematic glucose levels, or treatment decisions contrary to the patient's actual glycemic state.

Solstice has established a target of ≥ 99% of paired data points in Zones A and B, which is consistent with iCGM expectations. This is a demanding threshold, and achieving it will require both high mean accuracy (as captured by the MARD metric) and low variability in sensor readings — that is, the absence of outlier readings that would fall into Zones C through E.

FDA may also request additional point accuracy metrics beyond the Clarke/Consensus Error Grid analysis. Specifically, the September 2023 guidance suggests that manufacturers provide data on the percentage of CGM readings that fall within:

• ± 15 mg/dL of the reference glucose value, for reference glucose concentrations < 100 mg/dL; and

• ± 15% of the reference glucose value, for reference glucose concentrations ≥ 100 mg/dL.

These point accuracy thresholds provide a more granular view of sensor accuracy than the Error Grid analysis alone and are commonly reported in CGM clinical studies. Solstice should design the LUMINA-US clinical study to capture and report these metrics in addition to the primary MARD and Error Grid endpoints.

3. Alarm/Alert Performance

iCGM devices must demonstrate adequate hypoglycemia and hyperglycemia alert performance as part of the special controls assessment. Alert performance is clinically important because users and, in the iCGM context, secondary devices rely on the CGM system's alerts to detect and respond to dangerous glucose excursions. An iCGM device that fails to alert on a hypoglycemic event, or that generates excessive false alerts, would compromise the safety and effectiveness of any integrated system that relies on the iCGM's data output.

The Lumina CGM System's alert latency specification is ≤ 5 minutes from the time of the sensor glucose reading to the time of user notification on the R7 reader device or the Lumina Mobile App. This specification describes the end-to-end delay between sensor measurement and user-facing notification, encompassing sensor signal processing, BLE data transmission from the C14 sensor to the R7 reader, algorithm computation, alert threshold comparison, and display rendering.

The question of whether a five-minute alert latency meets FDA's expectations for iCGM devices warrants discussion at the Pre-Sub meeting. The September 2023 guidance does not specify a precise maximum alert latency, but does indicate that alert performance should be assessed in terms of sensitivity (the probability of detecting a true glucose excursion), specificity (the probability of not alerting when glucose is within the normal range), and timeliness. A five-minute latency may be acceptable, but Solstice should be prepared to justify this specification in the context of the clinical scenarios in which timely alert performance is most critical — particularly nocturnal hypoglycemia and exercise-induced glucose fluctuations.

Additionally, the configurable alert thresholds on the Lumina R7 reader and mobile application must be evaluated against iCGM special controls. FDA may have expectations regarding default alert threshold settings, the range of user-configurable thresholds, and the availability of predictive alerts (alerts triggered before the glucose concentration reaches the threshold, based on the rate of glucose change). The LuminaPredict Algorithm v2.1, which provides predictive glucose trend information, may be relevant in this context, and Solstice should consider whether the algorithm's predictive capabilities can be leveraged to enhance alert performance for iCGM purposes.

4. Sensor Reliability and Functional Life

The iCGM special controls require demonstration that the sensor maintains reliable and consistent performance throughout its specified functional life. For the Lumina C14 sensor, the specified functional life is fourteen (14) days (336 hours), which aligns with the secondary predicate device (NovaSense GlucoTrack NX-700, K230489) and is within the range of currently marketed iCGM devices.

Consistent performance throughout the sensor's functional life means that the iCGM performance criteria — including MARD ≤ 9.0% and ≥ 99% Zones A+B — must be met not just as overall metrics across the entire wear period, but at each stage of the sensor's life. FDA may request time-stratified accuracy data (e.g., Days 1–3, Days 4–7, Days 8–10, Days 11–14) to assess whether sensor performance degrades over time in a manner that could compromise the safety and effectiveness of the iCGM system during the later portion of the wear period.

The Lumina system's warm-up time specification of ≤ 60 minutes is also relevant to the functional life analysis. During the warm-up period following sensor insertion, the CGM sensor typically produces less accurate readings as the sensor equilibrates with the surrounding interstitial fluid. FDA's September 2023 guidance acknowledges that warm-up period readings may be excluded from accuracy calculations, provided that the manufacturer's labeling clearly instructs users not to rely on glucose readings during the warm-up period and that the device does not display glucose values or generate alerts during the warm-up period. Solstice should confirm that the Lumina system's firmware prevents the display of glucose values and the generation of alerts during the warm-up period, and that this behavior is clearly described in the labeling.

Sensor failure rate and early termination data will need to be captured in the LUMINA-US clinical study. FDA will expect data on the proportion of sensors that complete the full fourteen-day wear period versus those that fail or are removed early, the reasons for early termination (e.g., sensor detachment, loss of signal, user discomfort, adverse events), and the impact of early sensor failure on the overall accuracy dataset. High sensor failure rates could raise safety concerns and would need to be addressed in the device's labeling, including contraindications and user instructions regarding sensor replacement.

B. Design Verification and Validation Requirements

The iCGM special controls require comprehensive design verification and validation ("V&V") activities, including bench testing, biocompatibility testing, electromagnetic compatibility ("EMC") testing, and electrical safety testing. These requirements largely overlap with the standard 510(k) requirements for CGM devices but take on heightened significance in the iCGM context due to the device's intended interoperability with safety-critical secondary devices.

Bench Testing. The bench testing program for the Lumina CGM System must include, at a minimum, the following evaluations:

• Sensor accuracy testing against a laboratory-grade reference glucose analyzer (e.g., YSI 2300 STAT Plus) across the full measurement range (40–400 mg/dL) and across the full fourteen-day sensor life.

• Linearity testing to demonstrate a linear relationship between sensor output and reference glucose concentration across the measurement range.

• Precision testing to demonstrate the repeatability and reproducibility of sensor readings under controlled conditions.

• Drift testing to characterize and quantify any systematic change in sensor output over the fourteen-day wear period.

• Interference testing to evaluate the impact of known interferents on sensor accuracy. Common interferents for enzymatic electrochemical glucose sensors include acetaminophen (paracetamol), ascorbic acid (vitamin C), dopamine, uric acid, and other substances commonly found in interstitial fluid. The September 2023 guidance identifies specific interferents and concentration levels that should be tested, and Solstice should ensure that the interference testing program addresses all substances identified in the guidance.

Biocompatibility Testing. The Lumina C14 sensor is a subcutaneously implanted device with a wear duration of up to fourteen days, which classifies it as a surface-contacting, tissue/bone-contacting device with limited contact duration under ISO 10993-1:2018. The biocompatibility testing program has been outlined in our prior correspondence and is being conducted by Whitmore Laboratories Inc. (A2LA Certificate No. 3847.01), with a total budget of $485,000 and a target completion date of August 31, 2025. The biocompatibility testing scope includes cytotoxicity, sensitization, irritation, acute systemic toxicity, subacute/subchronic toxicity, genotoxicity, and implantation testing, consistent with the ISO 10993 series requirements applicable to the device's contact type and duration.

EMC Testing. The Lumina CGM System must demonstrate compliance with electromagnetic compatibility requirements per IEC 60601-1-2 (Medical electrical equipment — Part 1-2: General requirements for basic safety and essential performance — Collateral Standard: Electromagnetic disturbances — Requirements and tests). Given that the Lumina system uses BLE 5.2 wireless communication, EMC testing must address both the system's susceptibility to electromagnetic interference from external sources and its potential to cause electromagnetic interference that could affect other nearby medical devices.

Electrical Safety Testing. The Lumina R7 reader/transmitter must comply with applicable electrical safety standards for medical electrical equipment, including IEC 60601-1 (General requirements for basic safety and essential performance).

Software Verification and Validation. Software V&V activities must comply with IEC 62304:2006/A1:2015 (Medical device software — Software life cycle processes). The Lumina system's software components — including the C14 sensor firmware (v3.4.2), the R7 reader operating system (v2.1.0), the LuminaPredict Algorithm (v2.1), and the Lumina Mobile App (v1.0.3) — must each be verified and validated in accordance with IEC 62304 requirements applicable to the assigned software safety classification. As discussed further in Section IV.D below, the Lumina system's software has been classified at a level of concern of "Major," which is appropriate for an iCGM device whose software outputs directly influence therapeutic decision-making.

C. Clinical Evidence Requirements

FDA expects clinical data demonstrating iCGM performance criteria in the intended use population as part of any 510(k) submission seeking iCGM classification. While bench testing and analytical performance data are necessary, they are not sufficient alone; FDA requires clinical evidence from a prospective clinical study conducted in the United States using the commercial-equivalent version of the device.

Planned Pivotal Clinical Study. Solstice has planned a pivotal clinical study designated Protocol SBD-LUM-CL-001, titled "LUMINA-US," which will provide the clinical evidence required for the 510(k) submission. The key parameters of the LUMINA-US study are as follows:

• Study design: Prospective, single-arm, multicenter clinical study.

• Enrollment: Three hundred fifty (350) subjects, comprising one hundred seventy-five (175) subjects with Type 1 diabetes mellitus and one hundred seventy-five (175) subjects with Type 2 diabetes mellitus.

• Study sites: Six (6) U.S. clinical sites (sites to be identified and qualified prior to study commencement).

• Contract research organization: Veltrano Clinical Research Organization Inc. ("Veltrano CRO"), under the direction of Dr. Lisa Fontaine, Vice President of Clinical Operations.

• IRB oversight: Clearwater Institutional Review Board LLC (IRB Registration No. IRB-2019-04821) will serve as the central institutional review board for the study.

• Primary endpoint: Sensor accuracy as measured by MARD, comparing Lumina CGM glucose readings to paired reference glucose measurements obtained via YSI laboratory-grade glucose analyzer.

• Secondary endpoints: Safety (adverse event rate, serious adverse events, device-related adverse events) and user labeling comprehension (validated questionnaire assessing user understanding of device labeling, including indications for use, contraindications, warnings, and instructions for use).

• Study duration: Approximately six (6) months total, comprising approximately fourteen (14) weeks of subject enrollment, a fourteen (14)-day sensor wear period for each subject, and approximately eight (8) weeks of data analysis and study close-out. The planned study commencement date is September 15, 2025, with a planned completion date of March 15, 2026.

• Budget: Approximately $4,200,000 (calculated at $12,000 per subject for 350 subjects), encompassing site fees, investigator fees, Veltrano CRO management fees, reference glucose testing supplies and equipment, data management, biostatistical analysis, and clinical monitoring.

IDE Exemption. The LUMINA-US study is anticipated to qualify for an exemption from the Investigational Device Exemption ("IDE") requirements under 21 C.F.R. § 812.2(c)(3), which exempts from IDE requirements diagnostic devices that are used in accordance with their intended use and for which testing does not require an invasive sampling procedure, does not involve a significant risk to the subject, and complies with the requirements of 21 C.F.R. Part 812. Because the Lumina CGM System is a diagnostic device and the LUMINA-US study is designed as a non-significant risk ("NSR") diagnostic device study — the sensor is used in accordance with its intended diagnostic purpose, and the study does not involve any investigational therapeutic intervention — the IDE exemption is expected to apply. However, we recommend that the IDE exemption status be confirmed with FDA during the Pre-Sub meeting to avoid any procedural complications during study initiation.

Adequacy of Study Design for iCGM Classification. The LUMINA-US study as currently designed appears to be adequate to generate the clinical evidence required for iCGM classification. However, certain aspects of the study design should be reviewed against the September 2023 FDA guidance to ensure completeness. Specifically, Solstice should consider whether the study protocol includes the following elements, which FDA may expect for iCGM classification:

• Specific alarm/alert performance testing protocols, including assessment of alert sensitivity, specificity, and latency under controlled conditions (e.g., insulin-induced hypoglycemia clamp studies or meal challenge tests).

• Sensor life reliability data, including sensor survival analysis and failure mode characterization.

• Real-world use scenarios, including data collected during exercise, sleep, and periods of rapid glucose change.

• Assessment of sensor performance in challenging patient subpopulations, such as patients with high body mass index, patients using common interferent medications (e.g., acetaminophen), or patients with skin conditions that may affect sensor adhesion.

If any of these elements are not currently included in the LUMINA-US protocol, we recommend that Solstice discuss their inclusion or exclusion with FDA during the Pre-Sub meeting, to avoid the risk of a post-submission request for additional clinical data that could delay the review timeline.

D. Software and Cybersecurity Special Controls

The iCGM special controls include specific requirements for software documentation, cybersecurity, and data integrity. These requirements reflect the heightened importance of software reliability and security in devices whose data output is intended to drive automated therapeutic decision-making by secondary devices.

Software Documentation. The 510(k) submission for an iCGM device must include comprehensive software documentation in accordance with IEC 62304:2006/A1:2015 and FDA's guidance on software in medical devices. This documentation must cover the software development life cycle, including requirements specification, architecture design, detailed design, implementation, unit testing, integration testing, system testing, and release. Given that the Lumina system comprises multiple software components — sensor firmware, reader operating system, predictive algorithm, and mobile application — each component must be documented separately, and the interfaces between components must be clearly described and verified.

Software Bill of Materials (SBOM). FDA's September 2023 guidance document on "Cybersecurity in Medical Devices: Quality System Considerations and Content of Premarket Submissions" requires that manufacturers include a Software Bill of Materials in their premarket submissions. The SBOM is a comprehensive inventory of all software components used in the device, including commercial, open-source, and off-the-shelf software components, along with their version numbers, known vulnerabilities, and support status. The SBOM enables FDA to assess the cybersecurity risk profile of the device's software architecture. Solstice's engineering team (under the direction of Dr. Aisling Burke, CTO) should ensure that a complete and current SBOM is prepared and maintained for each software component of the Lumina CGM System.

Threat Modeling. Solstice has reported that threat modeling for the Lumina CGM System has been completed using the STRIDE framework (Spoofing, Tampering, Repudiation, Information disclosure, Denial of service, Elevation of privilege). The STRIDE threat model identifies potential cybersecurity threats to the device system and documents the mitigations implemented to address each identified threat. This is an appropriate framework for iCGM cybersecurity assessment, and the completed threat model should be documented in a format acceptable to FDA for inclusion in the 510(k) submission. We recommend that the threat model documentation specifically address the BLE 5.2 communication interface between the C14 sensor and the R7 reader, as this wireless interface is a potential attack vector that FDA will likely scrutinize.

Data Output Interface and Interoperability. A defining characteristic of iCGM devices is that they must provide glucose data in a format that is compatible with secondary digitally connected devices. The iCGM data output must include, at a minimum, the real-time glucose value, the timestamp of the measurement, a trend indicator (rate of glucose change), and a data quality indicator. The format and protocol used to transmit this data must be specified in the submission and documented in the device's labeling.

The Lumina CGM System uses BLE 5.2 as its wireless communication protocol. BLE 5.2 offers several advantages over earlier BLE versions, including improved data throughput, extended range, and enhanced connection stability. However, for iCGM purposes, the critical question is not the wireless protocol itself, but the data format and content transmitted over that protocol. Solstice should ensure that the data output from the Lumina system includes all data elements required by the iCGM special controls and is structured in a manner that secondary device manufacturers can reliably parse and interpret. FDA may expect compliance with industry-standard interoperability frameworks, such as the IEEE 11073 family of standards for health informatics and personal health device communication.

LuminaPredict Algorithm v2.1. The LuminaPredict Algorithm v2.1 is Solstice's proprietary glucose prediction algorithm, which uses sensor glucose data to generate predictive trend information and, potentially, predictive alerts. As a software component that directly influences the glucose data presented to users and secondary devices, the LuminaPredict Algorithm will be subject to rigorous FDA scrutiny. FDA will likely require detailed documentation of the algorithm's design, validation methodology, training data (if machine learning is involved), clinical performance characteristics (e.g., prediction accuracy, prediction horizon, false positive/negative rates), and failure mode analysis. Solstice should prepare comprehensive algorithm validation documentation as part of the 510(k) submission, and we recommend including specific questions about FDA's expectations for algorithm documentation in the Pre-Sub meeting package.

E. Labeling and Interoperability Requirements

The iCGM classification carries specific labeling requirements that distinguish iCGM devices from standard CGM devices. These labeling requirements are designed to communicate the device's interoperability capabilities and intended use with digitally connected medical devices, and to ensure that users, healthcare providers, and secondary device manufacturers have the information needed to safely and effectively use the iCGM system in integrated configurations.

Identification as iCGM. The device labeling must clearly identify the Lumina CGM System as an iCGM device and describe the types of secondary devices with which it is intended to be used. This may include general categories of secondary devices (e.g., "automated insulin dosing systems," "secondary glucose display devices," "insulin pump systems") rather than specific product names, reflecting the interoperability framework's intention that secondary device manufacturers be able to reference the iCGM without bilateral agreements or coordinated submissions.

Interoperability Statements. The labeling must include statements describing the device's interoperability capabilities, the data output format and protocol, and any limitations on interoperability. For example, the labeling should specify that the device provides glucose data via BLE 5.2 in a specified format, and should describe any conditions under which interoperability may be impaired (e.g., wireless interference, distance limitations, environmental conditions).

Secondary Device Integration Strategy. Solstice should consider and document its intended strategy for secondary device integration. While the iCGM framework does not require Solstice to identify specific secondary device partners in the 510(k) submission, Solstice's commercial strategy will benefit from a clear articulation of the types of secondary devices with which the Lumina iCGM is intended to interface. Potential categories of secondary devices include:

• AID systems (also known as "closed-loop" or "artificial pancreas" systems)

• Secondary glucose display devices (e.g., smartwatch applications, caregiver monitoring devices)

• Insulin pumps with CGM data input capability

• Diabetes data management platforms

Solstice should confirm with its management team (Dr. Eoin Gallagher, CEO, and Dr. Aisling Burke, CTO) whether there are any known plans or ongoing discussions regarding partnerships with AID system manufacturers or other secondary device manufacturers. Such partnerships, if formalized, could strengthen the iCGM value proposition and be referenced in the submission.

Future Submission Implications. A significant commercial advantage of iCGM classification is that once the Lumina system is cleared as an iCGM, secondary device manufacturers can reference the Lumina iCGM in their own premarket submissions without requiring Solstice to file a new 510(k) for each integrated configuration. This "open platform" model is a cornerstone of the iCGM framework and represents a major departure from the traditional approach, which required the CGM manufacturer to participate in each integrated system's regulatory submission. For Solstice, this means that achieving iCGM classification would unlock a potentially significant and recurring revenue stream through integration partnerships, without the associated regulatory cost and timeline burden of participating in each partner's submission.

Contraindications, Warnings, and Limitations. The labeling must include appropriate contraindications, warnings, and limitations, including:

• Whether the device is cleared for adjunctive or non-adjunctive use. Adjunctive use means the CGM data is intended to supplement, not replace, blood glucose information obtained from standard blood glucose monitoring devices for diabetes treatment decisions. Non-adjunctive use means the CGM data can be used directly for diabetes treatment decisions, including insulin dosing, without a confirmatory fingerstick blood glucose test. The distinction is clinically significant and affects labeling claims, user instructions, and the clinical evidence burden.

• Warnings related to conditions that may affect sensor accuracy (e.g., use during MRI procedures, use with certain medications, extreme temperatures).

• Limitations on the user population (e.g., age restrictions, exclusion of pregnant women or patients on dialysis, if applicable).

The question of whether Solstice will seek a non-adjunctive use claim is an important strategic decision that should be discussed at the Pre-Sub meeting. Non-adjunctive use claims are becoming increasingly common for iCGM devices and are a significant competitive differentiator, but they require demonstration of a higher accuracy standard and more robust clinical evidence than adjunctive use claims.

F. Quality System Requirements

The iCGM special controls require compliance with 21 C.F.R. Part 820, the Quality System Regulation ("QSR"), which establishes current good manufacturing practice ("cGMP") requirements for medical devices marketed in the United States. The QSR covers all aspects of the device manufacturing process, including management controls, design controls, production and process controls, corrective and preventive action ("CAPA"), document controls, purchasing controls, and servicing.

Solstice holds ISO 13485:2016 quality management system certification, certified by Meridian Conformity Assessment GmbH (NB 0483). ISO 13485:2016 is the international quality management system standard for medical device manufacturers and covers substantially the same subject matter as the QSR. While there are differences between ISO 13485 and the QSR — particularly with respect to design controls under 21 C.F.R. § 820.30, complaint handling, and CAPA procedures — the two frameworks are broadly aligned, and FDA has been working toward harmonization of the QSR with ISO 13485.

FDA published a final rule in February 2024 (effective February 2, 2026) that will align the QSR more closely with ISO 13485:2016 through adoption of the Medical Device Single Audit Program ("MDSAP") framework. However, until the effective date of the final rule, Solstice must ensure compliance with the current QSR requirements, including the design controls provisions of 21 C.F.R. § 820.30. Solstice should conduct a gap analysis between its existing ISO 13485 quality management system and the current QSR requirements to identify and remediate any areas of non-conformity prior to 510(k) submission. This is particularly important with respect to design controls documentation, which FDA will review as part of the 510(k) submission and which may be subject to pre-approval inspection by FDA's Office of Regulatory Affairs.

V. Comparison: iCGM Classification vs. Standard 510(k) CGM Classification

A. Pathway Options

Solstice has two primary regulatory pathway options for the Lumina CGM System's U.S. market authorization, both of which involve a traditional 510(k) premarket notification submission under 21 C.F.R. Part 807, Subpart E:

Option 1: Traditional 510(k) with Standard CGM Classification (Non-iCGM). Under this option, Solstice would submit a traditional 510(k) seeking classification of the Lumina CGM System as a standard (non-integrated) CGM device under product code QKQ and 21 C.F.R. § 862.1355. This pathway requires demonstration of substantial equivalence to a legally marketed predicate device and compliance with the general and special controls applicable to standard CGM devices. The analytical performance bar for a standard CGM device is lower than for an iCGM device — while a MARD of ≤ 9.0% would be favorable, it is not a formal requirement for standard CGM classification. However, a standard CGM classification would limit the Lumina system's interoperability claims and would preclude integration with AID systems or other secondary devices without separate 510(k) clearances for each integrated configuration.

Option 2: Traditional 510(k) with iCGM Classification. Under this option, Solstice would submit a traditional 510(k) seeking classification of the Lumina CGM System as an iCGM device under product code QKQ and 21 C.F.R. § 862.1355, with compliance with the iCGM special controls established under DEN170088 and the March 2024 reclassification order. This pathway requires demonstration of substantial equivalence to a legally marketed predicate device (or, alternatively, to a legally marketed iCGM device) and compliance with the more stringent iCGM special controls, including the ≤ 9.0% MARD threshold, ≥ 99% Zones A+B, and all software, cybersecurity, interoperability, and labeling requirements discussed in Section IV above. The iCGM classification, while requiring a higher performance bar, offers the interoperability and integration advantages that are central to Solstice's commercial strategy.

De Novo vs. 510(k). An important threshold question is whether Solstice would need to file a De Novo classification request to obtain iCGM classification, or whether a 510(k) referencing existing legally marketed devices is sufficient. The answer is that a De Novo petition is not required. The De Novo classification order DEN170088 established the iCGM classification and created a pathway for subsequent devices to obtain iCGM classification through the 510(k) premarket notification process. Specifically, once a De Novo classification order is granted, subsequent devices of the same type can seek 510(k) clearance by demonstrating substantial equivalence to legally marketed devices within the classification, provided they comply with the applicable special controls. Therefore, Solstice can pursue iCGM classification through a traditional 510(k) submission, provided it identifies an appropriate predicate device and demonstrates compliance with the iCGM special controls.

B. Analysis of Predicate Devices' iCGM Status

A critical consideration for Solstice's iCGM strategy is the iCGM classification status of the identified predicate devices — the NovaSense GlucoTrack NX-500 (K211034) and the NovaSense GlucoTrack NX-700 (K230489).

If either or both of the identified predicate devices were cleared by FDA as iCGM devices, then Solstice can straightforwardly demonstrate substantial equivalence to an iCGM predicate and pursue iCGM classification through the 510(k) pathway. In this scenario, Solstice would need to demonstrate both (i) substantial equivalence to the predicate device in terms of intended use and technological characteristics, and (ii) compliance with the iCGM special controls.

If neither predicate device was cleared as an iCGM device — that is, if both the NX-500 and NX-700 were cleared as standard (non-integrated) CGM devices — the pathway to iCGM classification through a 510(k) becomes more complex. In this scenario, Solstice would have several options:

1. Cite an additional iCGM predicate. Solstice could identify a legally marketed iCGM device (i.e., a device cleared under the iCGM classification established by DEN170088) as a predicate or reference device, in addition to the NovaSense devices. This would provide FDA with a clear classification basis for iCGM classification.

2. Pursue iCGM classification based on special controls compliance alone. Solstice could argue that iCGM classification is warranted based on the device's compliance with the iCGM special controls, even if the primary predicate is a non-iCGM device. This approach would require Solstice to demonstrate that the Lumina system meets all iCGM performance criteria and that iCGM classification is appropriate given the device's intended use and technological characteristics. FDA has accepted this approach in certain cases, but it may require additional justification in the submission.

3. File a De Novo classification request. As a last resort, if FDA determines that iCGM classification is not available through the 510(k) pathway given the non-iCGM status of the predicates, Solstice could file a De Novo classification request. However, this option is not preferred because the iCGM classification already exists — there is no need to establish a new classification — and the De Novo pathway would add significant time (typically 150 review days vs. 90 days for a 510(k)) and cost to the regulatory process.

We recommend that Solstice research the iCGM classification status of the NovaSense predicate devices as part of the Pre-Sub preparation. This information can be obtained from FDA's 510(k) database, the relevant decision summaries, and the predicate devices' labeling. If the predicates are non-iCGM, we recommend identifying at least one legally marketed iCGM device to cite as an additional predicate or reference device, and including a question on this topic in the Pre-Sub meeting package.

C. Advantages and Risks of Pursuing iCGM Classification

The decision to pursue iCGM classification involves a trade-off between the substantial commercial and strategic advantages of the iCGM label and the heightened performance and documentation requirements that iCGM classification entails. We summarize the key advantages and risks below.

Advantages of iCGM Classification:

• Interoperability without additional 510(k)s. Perhaps the most significant advantage of iCGM classification is that it enables interoperability with secondary devices — including AID systems, insulin pumps, and secondary display devices — without requiring Solstice to submit a new 510(k) for each integrated configuration. This dramatically reduces the time and cost of bringing integrated diabetes management solutions to market and positions the Lumina system as a platform for third-party integration.

• Enhanced market positioning and competitive differentiation. The iCGM label is increasingly recognized by healthcare providers, patients, and payers as a mark of quality and interoperability. Achieving iCGM classification would differentiate the Lumina system from NovaSense GlucoTrack products (particularly if those products are not iCGM-classified) and from other CGM systems that lack interoperability capabilities.

• Alignment with industry trends. The diabetes management industry is moving rapidly toward interoperable ecosystems in which CGM systems, insulin pumps, AID algorithms, and data management platforms work together seamlessly. iCGM classification aligns Solstice with this trend and positions the company to participate in the next generation of diabetes management solutions.

• Reimbursement facilitation. Several major U.S. payers, including the Centers for Medicare & Medicaid Services ("CMS"), have established coverage policies that favor or require iCGM-classified CGM devices. Achieving iCGM classification could facilitate favorable reimbursement decisions and accelerate commercial adoption.

Risks of iCGM Classification:

• Higher performance bar. The ≤ 9.0% MARD and ≥ 99% Zones A+B requirements are non-negotiable for iCGM classification. If the LUMINA-US clinical study fails to demonstrate compliance with these thresholds, Solstice will not be able to obtain iCGM classification and will need to fall back to standard CGM classification. This is the single largest risk associated with the iCGM strategy, and it underscores the importance of robust clinical study design and execution.

• Additional documentation burden. iCGM classification requires more extensive software documentation, cybersecurity documentation, and interoperability documentation than standard CGM classification. While much of this documentation should be prepared as part of good regulatory practice regardless of classification, the iCGM requirements are more specific and more prescriptive, and incomplete documentation could result in additional information requests from FDA.

• Potential for longer review or AI requests. If FDA's review team determines that the iCGM special controls documentation is incomplete or insufficient, the review timeline could be extended through additional information ("

MEMORANDUM
PRIVILEGED AND CONFIDENTIAL — ATTORNEY-CLIENT COMMUNICATION
From: Calderwood & Harkness LLP
Miriam Calloway, Partner, Healthcare & Life Sciences — Responsible Partner Amy Whitfield, Associate, Healthcare & Life Sciences — Lead Associate Sean Morrissey, Associate, Healthcare & Life Sciences — Working Associate
To: Dr. Niamh Tierney, Vice President of Regulatory Affairs, Solstice Biomedical Devices Ltd. Marcus Hale, Vice President of U.S. Operations, Solstice Biomedical Inc.
CC: Dr. Eoin Gallagher, Chief Executive Officer, Solstice Biomedical Devices Ltd. Dr. Aisling Burke, Chief Technology Officer, Solstice Biomedical Devices Ltd. Joel Strauss, Billing Partner, Calderwood & Harkness LLP
Date: May 2, 2025
Re: Analysis of Integrated Continuous Glucose Monitoring (iCGM) Classification and Applicable Special Controls — Solstice Lumina™ CGM System
Engagement Reference No.: 1037-00002
Right-click to update Table of Contents
I. Executive Summary
The purpose of this memorandum is to provide Solstice Biomedical Devices Ltd. and Solstice Biomedical Inc. (collectively, "Solstice") with a comprehensive legal and regulatory analysis of whether the Solstice Lumina™ CGM System — comprising the Lumina C14 implantable sensor and the Lumina R7 wearable reader/transmitter — qualifies for classification as an integrated continuous glucose monitoring ("iCGM") device under the U.S. Food and Drug Administration's ("FDA's") De Novo classification order DEN170088 and the applicable special controls established thereunder.
Based on our review of the applicable regulations, FDA guidance documents, the De Novo classification framework, the technical specifications of the Lumina CGM System, and the regulatory submissions of comparable predicate devices, we conclude that the Lumina CGM System is well-positioned to pursue iCGM classification, provided it meets the stringent analytical performance criteria established for iCGM devices. The key performance benchmarks include: (i) an overall Mean Absolute Relative Difference ("MARD") of ≤ 9.0%; (ii) ≥ 99% of paired CGM-reference data points falling within Zones A and B of the Clarke/Consensus Error Grid; and (iii) satisfaction of all other applicable iCGM special controls relating to alarm/alert performance, software and cybersecurity documentation, interoperability, labeling, and quality system requirements.
The strategic advantages of iCGM classification for Solstice's U.S. market entry are substantial. Under the iCGM framework, the Lumina CGM System would be eligible for interoperability with secondary display devices and automated insulin dosing ("AID") systems without requiring Solstice to obtain separate 510(k) clearances for each integrated device configuration. This would materially accelerate Solstice's ability to participate in the growing diabetes management ecosystem in the United States, enhance competitive positioning relative to existing CGM products, and potentially facilitate favorable reimbursement pathways given payer preference for iCGM-classified devices.
This memorandum is being provided in advance of the Pre-Submission ("Q-Sub" or "Pre-Sub") meeting with FDA's Center for Devices and Radiological Health ("CDRH"), Office of Health Technology 2 ("OHT2"), Division of Chemistry and Toxicology Devices, which is currently targeted for August 14, 2025. The analysis herein is intended to inform the questions that Solstice will present to FDA regarding the iCGM classification pathway and to frame the regulatory strategy for the Lumina system's 510(k) submission. We recommend that Solstice include specific questions regarding iCGM classification in the Pre-Sub meeting package, which is targeted for submission to FDA by June 16, 2025, consistent with the meeting request anticipated to be submitted on June 2, 2025.
The remainder of this memorandum is organized as follows: Section II provides background on the Lumina CGM System, Solstice's regulatory history, and the identified predicate devices. Section III describes the regulatory framework for iCGM classification, including the De Novo classification order and applicable FDA guidance. Section IV provides a detailed analysis of each category of iCGM special controls and their application to the Lumina system. Section V compares the iCGM classification pathway with the standard 510(k) CGM pathway. Section VI presents a gap analysis of the Lumina system's readiness for iCGM classification. Sections VII through XI address interoperability implications, freedom-to-operate considerations, recommended strategy and Pre-Sub meeting questions, timeline implications, and estimated cost implications. Section XII offers our conclusions.
II. Background
A. The Solstice Lumina™ CGM System
The Solstice Lumina™ CGM System is a continuous glucose monitoring system designed for real-time measurement of glucose concentrations in persons aged eighteen (18) years and older who have been diagnosed with Type 1 or Type 2 diabetes mellitus. The system comprises two device variants and associated software components, which together constitute a single system intended for submission to FDA.
Device Variant 1: Lumina C14 Sensor. The Lumina C14 is a subcutaneously implantable continuous glucose monitoring sensor with a maximum intended wear duration of fourteen (14) days (336 hours). The C14 sensor employs a fourth-generation enzymatic electrochemical biosensor utilizing Solstice's proprietary platinum-iridium electrode coating technology, designated "PtIr-4G." The PtIr-4G technology represents an advancement over prior-generation platinum electrode coatings and is designed to enhance sensor linearity, reduce signal drift over the sensor's functional life, and improve interference rejection characteristics. The C14 sensor communicates wirelessly with the Lumina R7 reader/transmitter via Bluetooth Low Energy ("BLE") 5.2 data transmission protocol.
Device Variant 2: Lumina R7 Reader/Transmitter. The Lumina R7 is a wearable reader/transmitter device designed to be worn on the user's upper arm. The R7 receives BLE data transmissions from the C14 sensor and provides the user with real-time glucose values, directional trend arrows indicating the rate of glucose change, and eight (8)-hour trend graphs. The R7 includes configurable hypoglycemia and hyperglycemia alerts, which can be set by the user to activate at user-defined glucose thresholds. The R7 communicates with the Solstice Lumina™ mobile application (available on iOS and Android platforms) via BLE, enabling users to view their glucose data on a smartphone or tablet device.
Key System Specifications. The system's key technical specifications, as documented in Solstice's design history file and communicated to this firm, are as follows:
•  Measurement range: 40–400 mg/dL
•  Warm-up time: ≤ 60 minutes from sensor insertion to first glucose reading
•  Alert latency: ≤ 5 minutes from sensor glucose reading to user notification on the R7 reader or Lumina Mobile App
•  Firmware/Software versions: Lumina Firmware v3.4.2 (C14 sensor), Lumina Reader OS v2.1.0 (R7 reader), LuminaPredict Algorithm v2.1 (proprietary glucose prediction algorithm), Lumina Mobile App v1.0.3
•  Anticipated product code: QKQ (Electrode, Glucose, Subcutaneous)
•  Anticipated regulation number: 21 C.F.R. § 862.1355 (Glucose test system)
•  Anticipated device class: Class II
•  Submission type planned: Traditional 510(k) covering both the C14 sensor and the R7 reader/transmitter as a single system
B. Solstice's Regulatory History and EU Market Status
Solstice has prior experience with FDA regulatory submissions. Solstice previously obtained 510(k) clearance for the GlucoStrip RX-200 Test Strip Reader, under 510(k) No. K192847, which was cleared by FDA on November 14, 2019. The GlucoStrip RX-200 was classified under product code NBW as a Class II device. This prior clearance is cited herein solely for the purpose of establishing Solstice's corporate pedigree and prior interaction with FDA's device review program; the GlucoStrip RX-200 is not being cited as a predicate device for the Lumina CGM System, as it is a fundamentally different device type (a blood glucose test strip reader rather than a continuous glucose monitor).
The Lumina CGM System has been commercially available in the European Union since September 2024. Solstice obtained EU Medical Device Regulation ("MDR") CE certification for the Lumina CGM System, issued by Meridian Conformity Assessment GmbH (Notified Body No. 0483), under Certificate No. MCA-2024-07319, dated September 12, 2024. Solstice additionally holds ISO 13485:2016 quality management system certification, also certified by Meridian Conformity Assessment GmbH. The EU commercial experience with the Lumina system provides Solstice with real-world performance data and post-market surveillance information that may be supportive — though not dispositive — in the U.S. regulatory submission context. As discussed further in Section IV below, FDA will require U.S.-based clinical data from the planned LUMINA-US pivotal study to support iCGM classification; EU data alone will not be sufficient.
The Lumina CGM System does not have any existing FDA clearance or approval in the United States. The 510(k) submission contemplated herein will be Solstice's initial U.S. market authorization application for the Lumina system.
C. Predicate Devices
Calderwood & Harkness, in coordination with Pinnacle Regulatory Consulting Group LLC ("Pinnacle Regulatory"), has identified the following predicate devices for the Lumina CGM System's 510(k) submission:
Primary Predicate Device: NovaSense GlucoTrack NX-500 CGM System. The NovaSense GlucoTrack NX-500 CGM System received 510(k) clearance under 510(k) No. K211034, cleared on June 18, 2022. The NX-500 is classified under product code QKQ as a Class II device. The NX-500 is an enzymatic electrochemical CGM sensor with a ten (10)-day sensor wear duration and BLE wireless data transmission to a dedicated reader device. The NX-500 provides a strong technological basis for substantial equivalence comparison with the Lumina C14/R7 system, given the shared fundamental technology (enzymatic electrochemical sensing) and intended use population.
Secondary Predicate Device (Reference Device): NovaSense GlucoTrack NX-700 CGM System. The NovaSense GlucoTrack NX-700 CGM System received 510(k) clearance under 510(k) No. K230489, cleared on March 7, 2024. The NX-700 is also classified under product code QKQ as a Class II device. The NX-700 features an extended fourteen (14)-day sensor wear duration and enhanced BLE 5.0 data transmission, along with an updated glucose prediction algorithm. The NX-700 is being cited as a secondary predicate device, particularly to support the Lumina system's fourteen-day wear duration claim and updated wireless transmission capabilities.
Both predicate devices are manufactured by NovaSense Medical Technologies Inc. ("NovaSense"), a Delaware corporation (File No. 5429876), headquartered at 4800 Innovation Parkway, San Diego, California 92121. NovaSense's Chief Executive Officer is David Reinhardt, and its Vice President of Regulatory Affairs is Dr. Karen Nishimura. NovaSense reported fiscal year 2024 revenue of approximately $1.24 billion, making it a significant competitor in the continuous glucose monitoring market. The regulatory status of the NovaSense predicate devices with respect to iCGM classification is a material consideration for Solstice's iCGM strategy and is analyzed further in Section V below.
III. Regulatory Framework for iCGM Classification
A. Historical Context: De Novo Classification Order DEN170088
The iCGM classification was established by FDA through a De Novo classification request, designated DEN170088, which was granted in 2018. The De Novo pathway, codified at 21 U.S.C. § 360c(f)(2) and 21 C.F.R. Part 860, Subpart D, permits FDA to classify novel medical devices of low to moderate risk for which there is no legally marketed predicate device. When FDA grants a De Novo classification request, it simultaneously creates a new regulatory classification that subsequent devices of the same type may reference through the traditional 510(k) premarket notification pathway.
The creation of the iCGM classification represented a significant regulatory innovation in the diabetes device space. Prior to DEN170088, CGM devices were classified as standard Class II medical devices under 21 C.F.R. § 862.1355, and any integration between a CGM system and a secondary device (such as an automated insulin dosing system or an insulin pump) required the integrated system to undergo a combined premarket review. This approach was inefficient, costly, and inhibited innovation in the emerging field of interoperable diabetes management systems.
Through DEN170088, FDA established the iCGM as a distinct regulatory classification within the broader category of glucose test systems. The iCGM classification was specifically designed to facilitate interoperability between CGM systems and secondary digitally connected devices within an integrated diabetes management ecosystem. Under this framework, an iCGM device that meets the specified special controls can be used with secondary devices — including AID systems, secondary display devices, and insulin pumps — without requiring each integrated configuration to undergo a separate FDA review. This "plug-and-play" regulatory model was intended to accelerate the development and commercialization of interoperable diabetes management systems while maintaining appropriate safeguards through stringent performance criteria.
iCGM devices are classified as Class II medical devices under 21 C.F.R. § 862.1355, with special controls that go beyond those applicable to standard (non-integrated) CGM devices. The special controls establish the performance, design, clinical evidence, labeling, software, cybersecurity, and quality system requirements that an iCGM device must satisfy in order to provide reasonable assurance of safety and effectiveness.
The critical distinction between iCGM and non-integrated CGM devices is that iCGM devices are specifically intended to be compatible with other digitally connected medical devices, and must meet specific accuracy and reliability criteria set forth in the special controls that ensure the glucose data output is sufficiently accurate and reliable for use by secondary devices in automated therapeutic decision-making. A non-integrated CGM device, by contrast, is intended for standalone use and does not carry interoperability labeling or the attendant performance obligations.
B. Applicable Regulation: 21 C.F.R. § 862.1355
The regulation number anticipated for the Solstice Lumina™ CGM System — 21 C.F.R. § 862.1355, titled "Glucose test system" — is the same regulation that governs iCGM devices. This regulation covers devices intended to measure glucose quantitatively in blood, interstitial fluid, or other body fluids. Under the current regulatory framework, both standard CGM devices and iCGM devices are classified under § 862.1355, with the distinction between the two classifications determined by the applicable special controls and the device's intended use with respect to interoperability.
FDA issued a reclassification order effective March 2024 that updated the classification framework for CGM devices under this regulation. The reclassification order consolidated several CGM device types under 21 C.F.R. § 862.1355 and modified the applicable special controls to reflect current technological capabilities and clinical evidence standards. The March 2024 reclassification order is relevant to Solstice's iCGM strategy because it updated certain performance expectations and documentation requirements that will apply to the Lumina CGM System's 510(k) submission. Specifically, the reclassification order clarified the relationship between standard CGM and iCGM special controls and confirmed that product code QKQ applies to subcutaneous glucose electrode sensors used in continuous monitoring systems, irrespective of whether the device seeks iCGM or standard CGM classification.
Product code QKQ, which is the product code anticipated for the Lumina CGM System, encompasses electrode-based glucose sensors designed for subcutaneous implantation and continuous glucose monitoring. This product code covers both the sensor component and the associated reader/transmitter when submitted as a system, consistent with Solstice's planned submission approach.
C. FDA Guidance: "Integrated Continuous Glucose Monitoring Systems" (September 2023)
In September 2023, FDA published a guidance document titled "Integrated Continuous Glucose Monitoring Systems," which provides detailed recommendations regarding the performance criteria, labeling requirements, and clinical evidence expectations for devices seeking iCGM classification. This guidance document is the most current and comprehensive statement of FDA's expectations for iCGM devices and will be a central reference point in both the Pre-Sub meeting discussion and the eventual 510(k) submission.
The September 2023 guidance document addresses several critical areas for iCGM classification. First, it describes the analytical accuracy performance criteria that iCGM devices must meet, including the overall MARD threshold, point accuracy requirements, and glucose range-specific performance benchmarks. Second, the guidance establishes alarm performance criteria, addressing the sensitivity, specificity, and latency of hypoglycemia and hyperglycemia alerts. Third, the guidance describes the data output requirements for interoperability, specifying the format and content of glucose data that an iCGM must provide to secondary devices. Fourth, the guidance outlines cybersecurity expectations for iCGM devices, reflecting the heightened security risks associated with devices that transmit glucose data to automated therapeutic systems.
It is important to note that, as with all FDA guidance documents, the September 2023 guidance is not legally binding on either FDA or device manufacturers. The guidance states that it "represents the current thinking of the Food and Drug Administration" and that "an alternative approach may be used if such approach satisfies the requirements of the applicable statutes and regulations." Notwithstanding this caveat, the September 2023 guidance represents FDA's most authoritative statement of its current expectations for iCGM devices, and we strongly recommend that Solstice treat the guidance's recommendations as the operative performance benchmarks for purposes of iCGM classification. Deviation from the guidance's recommendations without strong scientific justification would likely result in additional information requests during FDA review and potential delays in the 510(k) clearance timeline.
The guidance document will be a key input for the Pre-Sub meeting discussion, and we recommend that the Pre-Sub meeting package specifically reference the guidance and seek FDA's feedback on Solstice's proposed approach to meeting the guidance's recommendations.
IV. Special Controls Applicable to iCGM Devices
This Section provides a detailed analysis of each category of special controls applicable to iCGM devices and their application to the Solstice Lumina™ CGM System. The special controls established under De Novo classification order DEN170088, as updated by the March 2024 reclassification order, encompass the following categories: (A) analytical performance criteria; (B) design verification and validation requirements; (C) clinical evidence requirements; (D) software and cybersecurity special controls; (E) labeling and interoperability requirements; and (F) quality system requirements.
A. Analytical Performance Criteria
1. MARD (Mean Absolute Relative Difference) Requirement
The Mean Absolute Relative Difference, commonly referred to as MARD, is the primary accuracy metric used to evaluate CGM device performance. MARD quantifies the average deviation between CGM glucose readings and paired reference glucose measurements (typically obtained via YSI laboratory-grade glucose analyzer), expressed as a percentage of the reference value. A lower MARD value indicates higher CGM accuracy relative to the reference standard.
The iCGM special controls require demonstration of a MARD that is consistent with the safe and effective use of the device in conjunction with secondary digitally connected devices, including AID systems. FDA's September 2023 guidance document recommends an overall MARD of ≤ 9.0% as the benchmark for iCGM classification. This threshold reflects FDA's assessment that CGM data used to drive automated insulin dosing decisions must meet a higher accuracy standard than CGM data used solely for informational purposes.
Solstice has established a MARD target of ≤ 9.0% overall for the Lumina CGM System, which is aligned with the iCGM requirement. Achieving this target will be critical to iCGM classification, and Solstice should be aware that the MARD target is not simply a mean performance goal but must be demonstrated with statistical rigor across the full measurement range and across the full sensor wear duration.
Specifically, MARD must be demonstrated across the full measurement range of the Lumina system (40–400 mg/dL), and FDA is expected to require stratification of MARD performance by glycemic range. The three standard glycemic ranges for MARD stratification are:
•  Hypoglycemic range: < 70 mg/dL
•  Euglycemic range: 70–180 mg/dL
•  Hyperglycemic range: > 180 mg/dL
Accurate performance in the hypoglycemic range is of particular importance for iCGM devices, because inaccurate glucose readings in the low glucose range can lead to inappropriate insulin dosing by AID systems, with potentially severe clinical consequences including insulin-induced hypoglycemia. FDA may establish more stringent MARD sub-thresholds for the hypoglycemic range, and Solstice should anticipate that FDA will scrutinize hypoglycemic-range accuracy data with particular rigor.
In addition, MARD performance must be maintained across the full fourteen (14)-day sensor wear duration (336 hours) of the Lumina C14 sensor. FDA is expected to require analysis of MARD performance as a function of sensor age, including degradation analysis demonstrating that sensor accuracy does not deteriorate below the iCGM threshold over the sensor's functional life. This degradation analysis should account for known phenomena such as membrane biofouling, enzyme activity decay, and electrode drift, all of which can affect sensor accuracy over extended wear periods. Solstice's PtIr-4G electrode coating technology is designed to mitigate certain of these degradation mechanisms, and Solstice should be prepared to present data demonstrating the stability of sensor performance over the full fourteen-day wear period.
2. Consensus Error Grid / Point Accuracy
In addition to the overall MARD requirement, the iCGM special controls require that a device demonstrate high point accuracy as measured by the Clarke Error Grid Analysis or the Consensus Error Grid Analysis. Specifically, the iCGM special controls require that ≥ 99% of paired CGM-reference data points fall within Zones A and B of the Clarke or Consensus Error Grid. Zone A represents glucose values within 20% of the reference value (or within 20 mg/dL for reference values below 70 mg/dL) — clinically accurate readings that would lead to correct treatment decisions. Zone B represents glucose values that would lead to benign treatment decisions or no treatment. Points falling outside Zones A and B (i.e., in Zones C, D, or E) represent clinically significant errors that could lead to unnecessary treatment, failure to detect problematic glucose levels, or treatment decisions contrary to the patient's actual glycemic state.
Solstice has established a target of ≥ 99% of paired data points in Zones A and B, which is consistent with iCGM expectations. This is a demanding threshold, and achieving it will require both high mean accuracy (as captured by the MARD metric) and low variability in sensor readings — that is, the absence of outlier readings that would fall into Zones C through E.
FDA may also request additional point accuracy metrics beyond the Clarke/Consensus Error Grid analysis. Specifically, the September 2023 guidance suggests that manufacturers provide data on the percentage of CGM readings that fall within:
•  ± 15 mg/dL of the reference glucose value, for reference glucose concentrations < 100 mg/dL; and
•  ± 15% of the reference glucose value, for reference glucose concentrations ≥ 100 mg/dL.
These point accuracy thresholds provide a more granular view of sensor accuracy than the Error Grid analysis alone and are commonly reported in CGM clinical studies. Solstice should design the LUMINA-US clinical study to capture and report these metrics in addition to the primary MARD and Error Grid endpoints.
3. Alarm/Alert Performance
iCGM devices must demonstrate adequate hypoglycemia and hyperglycemia alert performance as part of the special controls assessment. Alert performance is clinically important because users and, in the iCGM context, secondary devices rely on the CGM system's alerts to detect and respond to dangerous glucose excursions. An iCGM device that fails to alert on a hypoglycemic event, or that generates excessive false alerts, would compromise the safety and effectiveness of any integrated system that relies on the iCGM's data output.
The Lumina CGM System's alert latency specification is ≤ 5 minutes from the time of the sensor glucose reading to the time of user notification on the R7 reader device or the Lumina Mobile App. This specification describes the end-to-end delay between sensor measurement and user-facing notification, encompassing sensor signal processing, BLE data transmission from the C14 sensor to the R7 reader, algorithm computation, alert threshold comparison, and display rendering.
The question of whether a five-minute alert latency meets FDA's expectations for iCGM devices warrants discussion at the Pre-Sub meeting. The September 2023 guidance does not specify a precise maximum alert latency, but does indicate that alert performance should be assessed in terms of sensitivity (the probability of detecting a true glucose excursion), specificity (the probability of not alerting when glucose is within the normal range), and timeliness. A five-minute latency may be acceptable, but Solstice should be prepared to justify this specification in the context of the clinical scenarios in which timely alert performance is most critical — particularly nocturnal hypoglycemia and exercise-induced glucose fluctuations.
Additionally, the configurable alert thresholds on the Lumina R7 reader and mobile application must be evaluated against iCGM special controls. FDA may have expectations regarding default alert threshold settings, the range of user-configurable thresholds, and the availability of predictive alerts (alerts triggered before the glucose concentration reaches the threshold, based on the rate of glucose change). The LuminaPredict Algorithm v2.1, which provides predictive glucose trend information, may be relevant in this context, and Solstice should consider whether the algorithm's predictive capabilities can be leveraged to enhance alert performance for iCGM purposes.
4. Sensor Reliability and Functional Life
The iCGM special controls require demonstration that the sensor maintains reliable and consistent performance throughout its specified functional life. For the Lumina C14 sensor, the specified functional life is fourteen (14) days (336 hours), which aligns with the secondary predicate device (NovaSense GlucoTrack NX-700, K230489) and is within the range of currently marketed iCGM devices.
Consistent performance throughout the sensor's functional life means that the iCGM performance criteria — including MARD ≤ 9.0% and ≥ 99% Zones A+B — must be met not just as overall metrics across the entire wear period, but at each stage of the sensor's life. FDA may request time-stratified accuracy data (e.g., Days 1–3, Days 4–7, Days 8–10, Days 11–14) to assess whether sensor performance degrades over time in a manner that could compromise the safety and effectiveness of the iCGM system during the later portion of the wear period.
The Lumina system's warm-up time specification of ≤ 60 minutes is also relevant to the functional life analysis. During the warm-up period following sensor insertion, the CGM sensor typically produces less accurate readings as the sensor equilibrates with the surrounding interstitial fluid. FDA's September 2023 guidance acknowledges that warm-up period readings may be excluded from accuracy calculations, provided that the manufacturer's labeling clearly instructs users not to rely on glucose readings during the warm-up period and that the device does not display glucose values or generate alerts during the warm-up period. Solstice should confirm that the Lumina system's firmware prevents the display of glucose values and the generation of alerts during the warm-up period, and that this behavior is clearly described in the labeling.
Sensor failure rate and early termination data will need to be captured in the LUMINA-US clinical study. FDA will expect data on the proportion of sensors that complete the full fourteen-day wear period versus those that fail or are removed early, the reasons for early termination (e.g., sensor detachment, loss of signal, user discomfort, adverse events), and the impact of early sensor failure on the overall accuracy dataset. High sensor failure rates could raise safety concerns and would need to be addressed in the device's labeling, including contraindications and user instructions regarding sensor replacement.
B. Design Verification and Validation Requirements
The iCGM special controls require comprehensive design verification and validation ("V&V") activities, including bench testing, biocompatibility testing, electromagnetic compatibility ("EMC") testing, and electrical safety testing. These requirements largely overlap with the standard 510(k) requirements for CGM devices but take on heightened significance in the iCGM context due to the device's intended interoperability with safety-critical secondary devices.
Bench Testing. The bench testing program for the Lumina CGM System must include, at a minimum, the following evaluations:
•  Sensor accuracy testing against a laboratory-grade reference glucose analyzer (e.g., YSI 2300 STAT Plus) across the full measurement range (40–400 mg/dL) and across the full fourteen-day sensor life.
•  Linearity testing to demonstrate a linear relationship between sensor output and reference glucose concentration across the measurement range.
•  Precision testing to demonstrate the repeatability and reproducibility of sensor readings under controlled conditions.
•  Drift testing to characterize and quantify any systematic change in sensor output over the fourteen-day wear period.
•  Interference testing to evaluate the impact of known interferents on sensor accuracy. Common interferents for enzymatic electrochemical glucose sensors include acetaminophen (paracetamol), ascorbic acid (vitamin C), dopamine, uric acid, and other substances commonly found in interstitial fluid. The September 2023 guidance identifies specific interferents and concentration levels that should be tested, and Solstice should ensure that the interference testing program addresses all substances identified in the guidance.
Biocompatibility Testing. The Lumina C14 sensor is a subcutaneously implanted device with a wear duration of up to fourteen days, which classifies it as a surface-contacting, tissue/bone-contacting device with limited contact duration under ISO 10993-1:2018. The biocompatibility testing program has been outlined in our prior correspondence and is being conducted by Whitmore Laboratories Inc. (A2LA Certificate No. 3847.01), with a total budget of $485,000 and a target completion date of August 31, 2025. The biocompatibility testing scope includes cytotoxicity, sensitization, irritation, acute systemic toxicity, subacute/subchronic toxicity, genotoxicity, and implantation testing, consistent with the ISO 10993 series requirements applicable to the device's contact type and duration.
EMC Testing. The Lumina CGM System must demonstrate compliance with electromagnetic compatibility requirements per IEC 60601-1-2 (Medical electrical equipment — Part 1-2: General requirements for basic safety and essential performance — Collateral Standard: Electromagnetic disturbances — Requirements and tests). Given that the Lumina system uses BLE 5.2 wireless communication, EMC testing must address both the system's susceptibility to electromagnetic interference from external sources and its potential to cause electromagnetic interference that could affect other nearby medical devices.
Electrical Safety Testing. The Lumina R7 reader/transmitter must comply with applicable electrical safety standards for medical electrical equipment, including IEC 60601-1 (General requirements for basic safety and essential performance).
Software Verification and Validation. Software V&V activities must comply with IEC 62304:2006/A1:2015 (Medical device software — Software life cycle processes). The Lumina system's software components — including the C14 sensor firmware (v3.4.2), the R7 reader operating system (v2.1.0), the LuminaPredict Algorithm (v2.1), and the Lumina Mobile App (v1.0.3) — must each be verified and validated in accordance with IEC 62304 requirements applicable to the assigned software safety classification. As discussed further in Section IV.D below, the Lumina system's software has been classified at a level of concern of "Major," which is appropriate for an iCGM device whose software outputs directly influence therapeutic decision-making.
C. Clinical Evidence Requirements
FDA expects clinical data demonstrating iCGM performance criteria in the intended use population as part of any 510(k) submission seeking iCGM classification. While bench testing and analytical performance data are necessary, they are not sufficient alone; FDA requires clinical evidence from a prospective clinical study conducted in the United States using the commercial-equivalent version of the device.
Planned Pivotal Clinical Study. Solstice has planned a pivotal clinical study designated Protocol SBD-LUM-CL-001, titled "LUMINA-US," which will provide the clinical evidence required for the 510(k) submission. The key parameters of the LUMINA-US study are as follows:
•  Study design: Prospective, single-arm, multicenter clinical study.
•  Enrollment: Three hundred fifty (350) subjects, comprising one hundred seventy-five (175) subjects with Type 1 diabetes mellitus and one hundred seventy-five (175) subjects with Type 2 diabetes mellitus.
•  Study sites: Six (6) U.S. clinical sites (sites to be identified and qualified prior to study commencement).
•  Contract research organization: Veltrano Clinical Research Organization Inc. ("Veltrano CRO"), under the direction of Dr. Lisa Fontaine, Vice President of Clinical Operations.
•  IRB oversight: Clearwater Institutional Review Board LLC (IRB Registration No. IRB-2019-04821) will serve as the central institutional review board for the study.
•  Primary endpoint: Sensor accuracy as measured by MARD, comparing Lumina CGM glucose readings to paired reference glucose measurements obtained via YSI laboratory-grade glucose analyzer.
•  Secondary endpoints: Safety (adverse event rate, serious adverse events, device-related adverse events) and user labeling comprehension (validated questionnaire assessing user understanding of device labeling, including indications for use, contraindications, warnings, and instructions for use).
•  Study duration: Approximately six (6) months total, comprising approximately fourteen (14) weeks of subject enrollment, a fourteen (14)-day sensor wear period for each subject, and approximately eight (8) weeks of data analysis and study close-out. The planned study commencement date is September 15, 2025, with a planned completion date of March 15, 2026.
•  Budget: Approximately $4,200,000 (calculated at $12,000 per subject for 350 subjects), encompassing site fees, investigator fees, Veltrano CRO management fees, reference glucose testing supplies and equipment, data management, biostatistical analysis, and clinical monitoring.
IDE Exemption. The LUMINA-US study is anticipated to qualify for an exemption from the Investigational Device Exemption ("IDE") requirements under 21 C.F.R. § 812.2(c)(3), which exempts from IDE requirements diagnostic devices that are used in accordance with their intended use and for which testing does not require an invasive sampling procedure, does not involve a significant risk to the subject, and complies with the requirements of 21 C.F.R. Part 812. Because the Lumina CGM System is a diagnostic device and the LUMINA-US study is designed as a non-significant risk ("NSR") diagnostic device study — the sensor is used in accordance with its intended diagnostic purpose, and the study does not involve any investigational therapeutic intervention — the IDE exemption is expected to apply. However, we recommend that the IDE exemption status be confirmed with FDA during the Pre-Sub meeting to avoid any procedural complications during study initiation.
Adequacy of Study Design for iCGM Classification. The LUMINA-US study as currently designed appears to be adequate to generate the clinical evidence required for iCGM classification. However, certain aspects of the study design should be reviewed against the September 2023 FDA guidance to ensure completeness. Specifically, Solstice should consider whether the study protocol includes the following elements, which FDA may expect for iCGM classification:
•  Specific alarm/alert performance testing protocols, including assessment of alert sensitivity, specificity, and latency under controlled conditions (e.g., insulin-induced hypoglycemia clamp studies or meal challenge tests).
•  Sensor life reliability data, including sensor survival analysis and failure mode characterization.
•  Real-world use scenarios, including data collected during exercise, sleep, and periods of rapid glucose change.
•  Assessment of sensor performance in challenging patient subpopulations, such as patients with high body mass index, patients using common interferent medications (e.g., acetaminophen), or patients with skin conditions that may affect sensor adhesion.
If any of these elements are not currently included in the LUMINA-US protocol, we recommend that Solstice discuss their inclusion or exclusion with FDA during the Pre-Sub meeting, to avoid the risk of a post-submission request for additional clinical data that could delay the review timeline.
D. Software and Cybersecurity Special Controls
The iCGM special controls include specific requirements for software documentation, cybersecurity, and data integrity. These requirements reflect the heightened importance of software reliability and security in devices whose data output is intended to drive automated therapeutic decision-making by secondary devices.
Software Documentation. The 510(k) submission for an iCGM device must include comprehensive software documentation in accordance with IEC 62304:2006/A1:2015 and FDA's guidance on software in medical devices. This documentation must cover the software development life cycle, including requirements specification, architecture design, detailed design, implementation, unit testing, integration testing, system testing, and release. Given that the Lumina system comprises multiple software components — sensor firmware, reader operating system, predictive algorithm, and mobile application — each component must be documented separately, and the interfaces between components must be clearly described and verified.
Software Bill of Materials (SBOM). FDA's September 2023 guidance document on "Cybersecurity in Medical Devices: Quality System Considerations and Content of Premarket Submissions" requires that manufacturers include a Software Bill of Materials in their premarket submissions. The SBOM is a comprehensive inventory of all software components used in the device, including commercial, open-source, and off-the-shelf software components, along with their version numbers, known vulnerabilities, and support status. The SBOM enables FDA to assess the cybersecurity risk profile of the device's software architecture. Solstice's engineering team (under the direction of Dr. Aisling Burke, CTO) should ensure that a complete and current SBOM is prepared and maintained for each software component of the Lumina CGM System.
Threat Modeling. Solstice has reported that threat modeling for the Lumina CGM System has been completed using the STRIDE framework (Spoofing, Tampering, Repudiation, Information disclosure, Denial of service, Elevation of privilege). The STRIDE threat model identifies potential cybersecurity threats to the device system and documents the mitigations implemented to address each identified threat. This is an appropriate framework for iCGM cybersecurity assessment, and the completed threat model should be documented in a format acceptable to FDA for inclusion in the 510(k) submission. We recommend that the threat model documentation specifically address the BLE 5.2 communication interface between the C14 sensor and the R7 reader, as this wireless interface is a potential attack vector that FDA will likely scrutinize.
Data Output Interface and Interoperability. A defining characteristic of iCGM devices is that they must provide glucose data in a format that is compatible with secondary digitally connected devices. The iCGM data output must include, at a minimum, the real-time glucose value, the timestamp of the measurement, a trend indicator (rate of glucose change), and a data quality indicator. The format and protocol used to transmit this data must be specified in the submission and documented in the device's labeling.
The Lumina CGM System uses BLE 5.2 as its wireless communication protocol. BLE 5.2 offers several advantages over earlier BLE versions, including improved data throughput, extended range, and enhanced connection stability. However, for iCGM purposes, the critical question is not the wireless protocol itself, but the data format and content transmitted over that protocol. Solstice should ensure that the data output from the Lumina system includes all data elements required by the iCGM special controls and is structured in a manner that secondary device manufacturers can reliably parse and interpret. FDA may expect compliance with industry-standard interoperability frameworks, such as the IEEE 11073 family of standards for health informatics and personal health device communication.
LuminaPredict Algorithm v2.1. The LuminaPredict Algorithm v2.1 is Solstice's proprietary glucose prediction algorithm, which uses sensor glucose data to generate predictive trend information and, potentially, predictive alerts. As a software component that directly influences the glucose data presented to users and secondary devices, the LuminaPredict Algorithm will be subject to rigorous FDA scrutiny. FDA will likely require detailed documentation of the algorithm's design, validation methodology, training data (if machine learning is involved), clinical performance characteristics (e.g., prediction accuracy, prediction horizon, false positive/negative rates), and failure mode analysis. Solstice should prepare comprehensive algorithm validation documentation as part of the 510(k) submission, and we recommend including specific questions about FDA's expectations for algorithm documentation in the Pre-Sub meeting package.
E. Labeling and Interoperability Requirements
The iCGM classification carries specific labeling requirements that distinguish iCGM devices from standard CGM devices. These labeling requirements are designed to communicate the device's interoperability capabilities and intended use with digitally connected medical devices, and to ensure that users, healthcare providers, and secondary device manufacturers have the information needed to safely and effectively use the iCGM system in integrated configurations.
Identification as iCGM. The device labeling must clearly identify the Lumina CGM System as an iCGM device and describe the types of secondary devices with which it is intended to be used. This may include general categories of secondary devices (e.g., "automated insulin dosing systems," "secondary glucose display devices," "insulin pump systems") rather than specific product names, reflecting the interoperability framework's intention that secondary device manufacturers be able to reference the iCGM without bilateral agreements or coordinated submissions.
Interoperability Statements. The labeling must include statements describing the device's interoperability capabilities, the data output format and protocol, and any limitations on interoperability. For example, the labeling should specify that the device provides glucose data via BLE 5.2 in a specified format, and should describe any conditions under which interoperability may be impaired (e.g., wireless interference, distance limitations, environmental conditions).
Secondary Device Integration Strategy. Solstice should consider and document its intended strategy for secondary device integration. While the iCGM framework does not require Solstice to identify specific secondary device partners in the 510(k) submission, Solstice's commercial strategy will benefit from a clear articulation of the types of secondary devices with which the Lumina iCGM is intended to interface. Potential categories of secondary devices include:
•  AID systems (also known as "closed-loop" or "artificial pancreas" systems)
•  Secondary glucose display devices (e.g., smartwatch applications, caregiver monitoring devices)
•  Insulin pumps with CGM data input capability
•  Diabetes data management platforms
Solstice should confirm with its management team (Dr. Eoin Gallagher, CEO, and Dr. Aisling Burke, CTO) whether there are any known plans or ongoing discussions regarding partnerships with AID system manufacturers or other secondary device manufacturers. Such partnerships, if formalized, could strengthen the iCGM value proposition and be referenced in the submission.
Future Submission Implications. A significant commercial advantage of iCGM classification is that once the Lumina system is cleared as an iCGM, secondary device manufacturers can reference the Lumina iCGM in their own premarket submissions without requiring Solstice to file a new 510(k) for each integrated configuration. This "open platform" model is a cornerstone of the iCGM framework and represents a major departure from the traditional approach, which required the CGM manufacturer to participate in each integrated system's regulatory submission. For Solstice, this means that achieving iCGM classification would unlock a potentially significant and recurring revenue stream through integration partnerships, without the associated regulatory cost and timeline burden of participating in each partner's submission.
Contraindications, Warnings, and Limitations. The labeling must include appropriate contraindications, warnings, and limitations, including:
•  Whether the device is cleared for adjunctive or non-adjunctive use. Adjunctive use means the CGM data is intended to supplement, not replace, blood glucose information obtained from standard blood glucose monitoring devices for diabetes treatment decisions. Non-adjunctive use means the CGM data can be used directly for diabetes treatment decisions, including insulin dosing, without a confirmatory fingerstick blood glucose test. The distinction is clinically significant and affects labeling claims, user instructions, and the clinical evidence burden.
•  Warnings related to conditions that may affect sensor accuracy (e.g., use during MRI procedures, use with certain medications, extreme temperatures).
•  Limitations on the user population (e.g., age restrictions, exclusion of pregnant women or patients on dialysis, if applicable).
The question of whether Solstice will seek a non-adjunctive use claim is an important strategic decision that should be discussed at the Pre-Sub meeting. Non-adjunctive use claims are becoming increasingly common for iCGM devices and are a significant competitive differentiator, but they require demonstration of a higher accuracy standard and more robust clinical evidence than adjunctive use claims.
F. Quality System Requirements
The iCGM special controls require compliance with 21 C.F.R. Part 820, the Quality System Regulation ("QSR"), which establishes current good manufacturing practice ("cGMP") requirements for medical devices marketed in the United States. The QSR covers all aspects of the device manufacturing process, including management controls, design controls, production and process controls, corrective and preventive action ("CAPA"), document controls, purchasing controls, and servicing.
Solstice holds ISO 13485:2016 quality management system certification, certified by Meridian Conformity Assessment GmbH (NB 0483). ISO 13485:2016 is the international quality management system standard for medical device manufacturers and covers substantially the same subject matter as the QSR. While there are differences between ISO 13485 and the QSR — particularly with respect to design controls under 21 C.F.R. § 820.30, complaint handling, and CAPA procedures — the two frameworks are broadly aligned, and FDA has been working toward harmonization of the QSR with ISO 13485.
FDA published a final rule in February 2024 (effective February 2, 2026) that will align the QSR more closely with ISO 13485:2016 through adoption of the Medical Device Single Audit Program ("MDSAP") framework. However, until the effective date of the final rule, Solstice must ensure compliance with the current QSR requirements, including the design controls provisions of 21 C.F.R. § 820.30. Solstice should conduct a gap analysis between its existing ISO 13485 quality management system and the current QSR requirements to identify and remediate any areas of non-conformity prior to 510(k) submission. This is particularly important with respect to design controls documentation, which FDA will review as part of the 510(k) submission and which may be subject to pre-approval inspection by FDA's Office of Regulatory Affairs.
V. Comparison: iCGM Classification vs. Standard 510(k) CGM Classification
A. Pathway Options
Solstice has two primary regulatory pathway options for the Lumina CGM System's U.S. market authorization, both of which involve a traditional 510(k) premarket notification submission under 21 C.F.R. Part 807, Subpart E:
Option 1: Traditional 510(k) with Standard CGM Classification (Non-iCGM). Under this option, Solstice would submit a traditional 510(k) seeking classification of the Lumina CGM System as a standard (non-integrated) CGM device under product code QKQ and 21 C.F.R. § 862.1355. This pathway requires demonstration of substantial equivalence to a legally marketed predicate device and compliance with the general and special controls applicable to standard CGM devices. The analytical performance bar for a standard CGM device is lower than for an iCGM device — while a MARD of ≤ 9.0% would be favorable, it is not a formal requirement for standard CGM classification. However, a standard CGM classification would limit the Lumina system's interoperability claims and would preclude integration with AID systems or other secondary devices without separate 510(k) clearances for each integrated configuration.
Option 2: Traditional 510(k) with iCGM Classification. Under this option, Solstice would submit a traditional 510(k) seeking classification of the Lumina CGM System as an iCGM device under product code QKQ and 21 C.F.R. § 862.1355, with compliance with the iCGM special controls established under DEN170088 and the March 2024 reclassification order. This pathway requires demonstration of substantial equivalence to a legally marketed predicate device (or, alternatively, to a legally marketed iCGM device) and compliance with the more stringent iCGM special controls, including the ≤ 9.0% MARD threshold, ≥ 99% Zones A+B, and all software, cybersecurity, interoperability, and labeling requirements discussed in Section IV above. The iCGM classification, while requiring a higher performance bar, offers the interoperability and integration advantages that are central to Solstice's commercial strategy.
De Novo vs. 510(k). An important threshold question is whether Solstice would need to file a De Novo classification request to obtain iCGM classification, or whether a 510(k) referencing existing legally marketed devices is sufficient. The answer is that a De Novo petition is not required. The De Novo classification order DEN170088 established the iCGM classification and created a pathway for subsequent devices to obtain iCGM classification through the 510(k) premarket notification process. Specifically, once a De Novo classification order is granted, subsequent devices of the same type can seek 510(k) clearance by demonstrating substantial equivalence to legally marketed devices within the classification, provided they comply with the applicable special controls. Therefore, Solstice can pursue iCGM classification through a traditional 510(k) submission, provided it identifies an appropriate predicate device and demonstrates compliance with the iCGM special controls.
B. Analysis of Predicate Devices' iCGM Status
A critical consideration for Solstice's iCGM strategy is the iCGM classification status of the identified predicate devices — the NovaSense GlucoTrack NX-500 (K211034) and the NovaSense GlucoTrack NX-700 (K230489).
If either or both of the identified predicate devices were cleared by FDA as iCGM devices, then Solstice can straightforwardly demonstrate substantial equivalence to an iCGM predicate and pursue iCGM classification through the 510(k) pathway. In this scenario, Solstice would need to demonstrate both (i) substantial equivalence to the predicate device in terms of intended use and technological characteristics, and (ii) compliance with the iCGM special controls.
If neither predicate device was cleared as an iCGM device — that is, if both the NX-500 and NX-700 were cleared as standard (non-integrated) CGM devices — the pathway to iCGM classification through a 510(k) becomes more complex. In this scenario, Solstice would have several options:
1.  Cite an additional iCGM predicate. Solstice could identify a legally marketed iCGM device (i.e., a device cleared under the iCGM classification established by DEN170088) as a predicate or reference device, in addition to the NovaSense devices. This would provide FDA with a clear classification basis for iCGM classification.
2.  Pursue iCGM classification based on special controls compliance alone. Solstice could argue that iCGM classification is warranted based on the device's compliance with the iCGM special controls, even if the primary predicate is a non-iCGM device. This approach would require Solstice to demonstrate that the Lumina system meets all iCGM performance criteria and that iCGM classification is appropriate given the device's intended use and technological characteristics. FDA has accepted this approach in certain cases, but it may require additional justification in the submission.
3.  File a De Novo classification request. As a last resort, if FDA determines that iCGM classification is not available through the 510(k) pathway given the non-iCGM status of the predicates, Solstice could file a De Novo classification request. However, this option is not preferred because the iCGM classification already exists — there is no need to establish a new classification — and the De Novo pathway would add significant time (typically 150 review days vs. 90 days for a 510(k)) and cost to the regulatory process.
We recommend that Solstice research the iCGM classification status of the NovaSense predicate devices as part of the Pre-Sub preparation. This information can be obtained from FDA's 510(k) database, the relevant decision summaries, and the predicate devices' labeling. If the predicates are non-iCGM, we recommend identifying at least one legally marketed iCGM device to cite as an additional predicate or reference device, and including a question on this topic in the Pre-Sub meeting package.
C. Advantages and Risks of Pursuing iCGM Classification
The decision to pursue iCGM classification involves a trade-off between the substantial commercial and strategic advantages of the iCGM label and the heightened performance and documentation requirements that iCGM classification entails. We summarize the key advantages and risks below.
Advantages of iCGM Classification:
•  Interoperability without additional 510(k)s. Perhaps the most significant advantage of iCGM classification is that it enables interoperability with secondary devices — including AID systems, insulin pumps, and secondary display devices — without requiring Solstice to submit a new 510(k) for each integrated configuration. This dramatically reduces the time and cost of bringing integrated diabetes management solutions to market and positions the Lumina system as a platform for third-party integration.
•  Enhanced market positioning and competitive differentiation. The iCGM label is increasingly recognized by healthcare providers, patients, and payers as a mark of quality and interoperability. Achieving iCGM classification would differentiate the Lumina system from NovaSense GlucoTrack products (particularly if those products are not iCGM-classified) and from other CGM systems that lack interoperability capabilities.
•  Alignment with industry trends. The diabetes management industry is moving rapidly toward interoperable ecosystems in which CGM systems, insulin pumps, AID algorithms, and data management platforms work together seamlessly. iCGM classification aligns Solstice with this trend and positions the company to participate in the next generation of diabetes management solutions.
•  Reimbursement facilitation. Several major U.S. payers, including the Centers for Medicare & Medicaid Services ("CMS"), have established coverage policies that favor or require iCGM-classified CGM devices. Achieving iCGM classification could facilitate favorable reimbursement decisions and accelerate commercial adoption.
Risks of iCGM Classification:
•  Higher performance bar. The ≤ 9.0% MARD and ≥ 99% Zones A+B requirements are non-negotiable for iCGM classification. If the LUMINA-US clinical study fails to demonstrate compliance with these thresholds, Solstice will not be able to obtain iCGM classification and will need to fall back to standard CGM classification. This is the single largest risk associated with the iCGM strategy, and it underscores the importance of robust clinical study design and execution.
•  Additional documentation burden. iCGM classification requires more extensive software documentation, cybersecurity documentation, and interoperability documentation than standard CGM classification. While much of this documentation should be prepared as part of good regulatory practice regardless of classification, the iCGM requirements are more specific and more prescriptive, and incomplete documentation could result in additional information requests from FDA.
•  Potential for longer review or AI requests. If FDA's review team determines that the iCGM special controls documentation is incomplete or insufficient, the review timeline could be extended through additional information ("

MEMORANDUM

Record

Parties

Dates

Amounts