PRIVILEGED AND CONFIDENTIAL — ATTORNEY-CLIENT COMMUNICATION / ATTORNEY WORK PRODUCT
MEMORANDUM
TO: Dr. Niamh Tierney, Vice President of Regulatory Affairs, Solstice Biomedical Devices Ltd. Marcus Hale, Vice President of U.S. Operations, Solstice Biomedical Inc.
FROM: Miriam Calloway, Responsible Partner, Healthcare & Life Sciences Practice Group, Calderwood & Harkness LLP Sean Morrissey, Working Associate, Healthcare & Life Sciences Practice Group, Calderwood & Harkness LLP
DATE: April 28, 2025
RE: Device Classification Analysis — Solstice Lumina™ CGM System; Product Code QKQ; 21 C.F.R. § 862.1355
ENGAGEMENT REF.: 1037-00002
This memorandum is a confidential attorney-client communication and constitutes attorney work product prepared in anticipation of regulatory proceedings. It is intended solely for the use of the addressees named above and authorized personnel of Solstice Biomedical Devices Ltd. and Solstice Biomedical Inc. Any dissemination, distribution, or copying of this memorandum, in whole or in part, to any third party without the prior written consent of Calderwood & Harkness LLP is strictly prohibited.
Right-click to update Table of Contents
I. PURPOSE AND SCOPE
The purpose of this memorandum is to provide Solstice Biomedical Devices Ltd. ("Solstice Ireland") and Solstice Biomedical Inc. ("Solstice U.S." and, together with Solstice Ireland, "Solstice" or the "Company") with a comprehensive legal analysis of the applicable U.S. Food and Drug Administration ("FDA") device classification for the Solstice Lumina™ Continuous Glucose Monitoring System (the "Lumina CGM System" or the "System"). The Lumina CGM System comprises two primary device components: the Lumina C14 implantable sensor (the "C14 sensor") and the Lumina R7 wearable reader/transmitter (the "R7 reader"). Together, these components form an integrated continuous glucose monitoring system intended for prescription use by adult patients with Type 1 or Type 2 diabetes mellitus.
This memorandum addresses the following topics in detail:
1. Identification of the appropriate product code. We analyze whether product code QKQ ("Electrode, Glucose, Subcutaneous") is the correct product code for the Lumina CGM System and distinguish QKQ from other potentially applicable product codes.
2. Identification of the applicable regulation number. We assess the applicability of 21 C.F.R. § 862.1355 ("Glucose test system") to the Lumina CGM System and examine the regulatory text, scope, and classification tier under that regulation.
3. Class II classification rationale. We set forth the basis for the Class II classification determination, including the requirement for premarket notification (510(k)) and the inapplicability of the Premarket Approval Application (PMA) pathway, provided that substantial equivalence to a legally marketed predicate device can be demonstrated.
4. Identification of applicable special controls. We identify and describe the special controls applicable to devices classified under product code QKQ, including analytical and clinical performance testing, biocompatibility, electromagnetic compatibility, software verification and validation, cybersecurity, and labeling requirements.
5. Impact of the FDA reclassification order effective March 2024. We analyze the March 2024 reclassification order that updated the classification framework for glucose test systems under 21 C.F.R. § 862.1355, and we assess its implications for the Lumina CGM System's submission strategy.
The intended audience for this memorandum is the Solstice regulatory affairs and U.S. operations teams. This analysis is intended to serve two primary functions: first, as a foundational internal strategy document to inform Solstice's regulatory decision-making regarding the Lumina CGM System's U.S. market entry; and second, as the analytical basis for the device classification discussion to be included in the Pre-Submission ("Pre-Sub") meeting request package that Solstice intends to submit to the FDA Center for Devices and Radiological Health ("CDRH") by June 16, 2025.
This memorandum should be read in conjunction with two companion documents prepared by Calderwood & Harkness in connection with this engagement: (a) the Regulatory Strategy Memorandum (1037-00002-Bramwell Grayson CPAs LLP), which addresses the broader U.S. regulatory strategy for the Lumina CGM System, including the substantial equivalence analysis, predicate device comparison, and submission timeline; and (b) the iCGM Special Controls Memorandum (1037-00002-iCGM), which addresses the specific question of whether the Lumina CGM System qualifies for classification as an integrated continuous glucose monitoring system ("iCGM") and the additional special controls applicable to iCGM-designated devices. The present memorandum provides the classification foundation upon which both of those companion analyses rely.
II. EXECUTIVE SUMMARY
Based on our analysis of the applicable FDA regulations, guidance documents, reclassification orders, and predicate device history, we conclude the following:
Classification. The Solstice Lumina™ CGM System is appropriately classified under product code QKQ ("Electrode, Glucose, Subcutaneous") and regulation number 21 C.F.R. § 862.1355 ("Glucose test system"). The System is a Class II medical device subject to premarket notification (510(k)) with applicable special controls. This classification applies to the Lumina CGM System as an integrated device system, encompassing both the C14 implantable sensor and the R7 wearable reader/transmitter within a single product code and a single 510(k) submission.
Reclassification Order. FDA's reclassification order effective March 2024 updated the classification framework for glucose test systems under 21 C.F.R. § 862.1355. That order consolidated certain CGM product codes, clarified the special controls applicable to CGM devices, and aligned the regulatory text with the current state of the technology. The March 2024 reclassification order directly affects the Lumina CGM System's submission pathway by confirming the Class II / 510(k) pathway for CGM systems of this type and by codifying the specific special controls that Solstice must address in its submission. The reclassification order is favorable to Solstice's regulatory strategy.
Predicate Devices. Both of the predicate devices that Solstice intends to rely upon for its substantial equivalence determination are classified under product code QKQ:
• Primary predicate: NovaSense GlucoTrack NX-500 (510(k) No. K211034, cleared June 18, 2022) — product code QKQ.
• Secondary predicate: NovaSense GlucoTrack NX-700 (510(k) No. K230489, cleared March 7, 2024) — product code QKQ.
The alignment of both predicate devices under the same product code as the Lumina CGM System provides strong support for Solstice's classification position and substantially reduces the risk that FDA will challenge the product code determination during its review.
Prior Solstice Clearance. Solstice's prior 510(k) clearance for the GlucoStrip RX-200 (510(k) No. K192847, cleared November 14, 2019) was obtained under product code NBW ("System, Test, Blood Glucose, Over the Counter"), which is a distinct product code applicable to self-monitoring blood glucose test strip reader systems. Product code NBW is not applicable to continuous glucose monitoring sensors and therefore the GlucoStrip RX-200 is not a suitable predicate for substantial equivalence purposes for the Lumina CGM System. However, this prior clearance demonstrates Solstice's established regulatory history with FDA and its familiarity with the FDA premarket notification process.
Submission Structure. The anticipated traditional 510(k) submission covering both the C14 sensor and the R7 reader as an integrated system is consistent with FDA's long-standing treatment of CGM systems as integrated device systems classified under a single product code. This approach is supported by the structure of the predicate device submissions for the NovaSense GlucoTrack NX-500 and NX-700, both of which were submitted and cleared as system-level submissions.
Special Controls. The applicable special controls encompass: (i) analytical performance testing (accuracy, precision, linearity, interference, sensor life); (ii) clinical performance testing (the LUMINA-US clinical study); (iii) biocompatibility testing (ISO 10993-1:2018); (iv) electromagnetic compatibility and electrical safety testing (IEC 60601-1-2, IEC 60601-1); (v) software verification and validation (IEC 62304); (vi) cybersecurity documentation; and (vii) labeling. These special controls are detailed in Section VI of this memorandum and are further addressed in the companion iCGM Special Controls Memorandum.
III. DEVICE DESCRIPTION
This Section provides a description of the Solstice Lumina™ CGM System, including its two primary components — the C14 implantable sensor and the R7 wearable reader/transmitter — as well as the associated mobile application. The device description set forth below is based on information provided by Solstice's engineering and regulatory affairs teams and is consistent with the technical specifications contained in Solstice's internal Design History File (DHF) for the Lumina CGM System (Document No. SBD-LUM-DHF-001, Revision 4.2, dated March 14, 2025).
III.A. Lumina C14 Implantable Sensor
The Lumina C14 is a subcutaneously implantable continuous glucose monitoring sensor designed to measure glucose concentrations in interstitial fluid. The sensor is inserted by the patient into the subcutaneous tissue, typically in the upper arm or abdomen, using a single-use, disposable insertion tool (the Lumina Inserter, Model LI-100) that is packaged with each sensor unit. The C14 sensor is a single-use, disposable component intended for a maximum wear duration of fourteen (14) days (336 hours) per sensor.
The C14 sensor employs Solstice's fourth-generation enzymatic electrochemical biosensor technology. This technology utilizes a glucose oxidase enzyme layer immobilized on the sensor electrode, which catalyzes the oxidation of glucose in the interstitial fluid. The resulting electrochemical reaction generates a measurable electrical current that is proportional to the glucose concentration in the surrounding interstitial fluid. The sensor incorporates Solstice's proprietary platinum-iridium electrode coating, designated "PtIr-4G" technology. The PtIr-4G coating is an advanced metallurgical formulation designed to enhance sensor sensitivity, reduce signal drift over the fourteen-day wear period, and improve resistance to biofouling — a common challenge in subcutaneous glucose sensors that can degrade sensor accuracy over time.
Key technical specifications of the C14 sensor include:
• Measurement range: 40–400 mg/dL (2.2–22.2 mmol/L)
• Sensor wear duration: Up to 14 days (336 hours)
• Warm-up time: ≤ 60 minutes from insertion to first glucose reading
• Measurement frequency: Glucose readings taken every 60 seconds; transmitted to the R7 reader every 5 minutes
• Wireless data transmission: Bluetooth Low Energy ("BLE") 5.2 protocol
• Operating temperature range: 10°C to 45°C (50°F to 113°F)
• Storage conditions: 2°C to 30°C (36°F to 86°F); shelf life of 18 months from date of manufacture
• Sterilization: Ethylene oxide (EO) sterilization; each sensor is individually packaged in a sterile, sealed pouch
• Firmware: Lumina Firmware v3.4.2, which controls sensor operation, signal processing, and BLE communication with the R7 reader
The C14 sensor is intended for use by persons aged 18 years and older who have been diagnosed with Type 1 or Type 2 diabetes mellitus. The sensor is intended to be used under the supervision of a healthcare professional, and the device is labeled for prescription use only.
III.B. Lumina R7 Wearable Reader/Transmitter
The Lumina R7 is a wearable reader and transmitter device designed to be worn on the patient's upper arm in close proximity to the implanted C14 sensor. The R7 reader serves as the primary user interface for the Lumina CGM System. It receives glucose data wirelessly from the C14 sensor via BLE 5.2, processes the data using Solstice's proprietary glucose prediction algorithm (designated "LuminaPredict Algorithm v2.1"), and displays the processed information to the user on an integrated touchscreen display.
The R7 reader provides the following information and functionality to the user:
• Real-time glucose values: The current glucose concentration, displayed in mg/dL or mmol/L (user-configurable), updated every 5 minutes.
• Trend arrows: Directional trend indicators showing the rate and direction of glucose change (e.g., rising rapidly, rising, stable, falling, falling rapidly).
• Trend graphs: An 8-hour historical trend graph showing glucose values over time, enabling the user to visualize glucose patterns.
• Configurable alerts: The R7 reader supports user-configurable hypoglycemia and hyperglycemia alerts with audible and vibratory notifications. Default alert thresholds are set at 70 mg/dL (low) and 250 mg/dL (high), but the user may adjust these thresholds within a clinically appropriate range under the direction of their healthcare provider.
• Alert latency: The system is designed to deliver user notifications within ≤ 5 minutes from the time the sensor generates a glucose reading to the time the user receives the corresponding notification on the R7 reader or the Lumina Mobile App.
The R7 reader also communicates wirelessly with the Solstice Lumina™ mobile application (the "Lumina Mobile App") installed on the patient's smartphone. The Lumina Mobile App is available for iOS (version 15.0 and later) and Android (version 12.0 and later) operating systems. The mobile application provides supplementary data display, historical data review, data sharing with healthcare providers, and cloud-based data storage. Communication between the R7 reader and the Lumina Mobile App occurs via BLE.
Key software versions associated with the R7 reader and the Lumina CGM System as a whole include:
• Lumina Reader OS v2.1.0: The operating system software running on the R7 reader's embedded processor.
• LuminaPredict Algorithm v2.1: The proprietary glucose prediction algorithm that processes raw sensor data to generate displayed glucose values, trend arrows, and alert determinations.
• Lumina Mobile App v1.0.3: The companion mobile application for iOS and Android platforms.
The R7 reader is rechargeable via a USB-C connection and has a battery life of approximately 7 days on a single charge under typical use conditions. The device is water-resistant to IP67 standards.
III.C. System-Level Classification Rationale
FDA has consistently treated continuous glucose monitoring systems as integrated device systems for classification and premarket submission purposes. Under this approach, the subcutaneous sensor and the associated reader/transmitter are viewed as components of a single device system, rather than as separate, independently classified devices. This integrated-system approach reflects the functional interdependence of the sensor and reader: the C14 sensor, standing alone, cannot display glucose information to the user; the R7 reader, standing alone, cannot measure glucose. Only when used together as a system do the components fulfill the System's intended use.
Accordingly, a single 510(k) submission covering both the C14 sensor and the R7 reader as an integrated system is the appropriate submission structure for the Lumina CGM System. This approach is consistent with the submissions made by NovaSense Technologies Inc. ("NovaSense") for both of the predicate devices identified by Solstice: the GlucoTrack NX-500 (K211034, cleared June 18, 2022) and the GlucoTrack NX-700 (K230489, cleared March 7, 2024). In each of those submissions, NovaSense submitted a single 510(k) covering both the sensor and the reader as a system, and FDA cleared the system under a single product code QKQ determination.
With respect to the Lumina Mobile App, FDA's guidance document "Policy for Device Software Functions and Mobile Medical Applications" (updated September 2022) provides that a mobile application that serves as an extension of a cleared medical device — for example, by displaying data generated by the device, enabling remote monitoring, or providing data storage — is generally considered an accessory to the parent device and may be addressed within the same premarket submission as the parent device. The Lumina Mobile App functions as an accessory to the Lumina CGM System by providing supplementary data display, historical data review, and data sharing capabilities. Accordingly, the Lumina Mobile App will be addressed within the same 510(k) submission as the C14 sensor and R7 reader. The software verification and validation documentation for the Lumina Mobile App will be included in the software documentation section of the 510(k) submission.
IV. PRODUCT CODE ANALYSIS — QKQ
IV.A. Product Code QKQ Definition
FDA product code QKQ is defined as "Electrode, Glucose, Subcutaneous." This product code falls within the Clinical Chemistry panel (Panel 75) and is reviewed by the Office of Health Technology 2 ("OHT2"), Division of Chemistry and Toxicology Devices, within the Center for Devices and Radiological Health ("CDRH"). Product code QKQ encompasses subcutaneous electrochemical glucose monitoring sensors and their associated reader/transmitter systems used for continuous glucose monitoring. The product code applies to devices that use a sensor element inserted beneath the skin to measure glucose concentrations in interstitial fluid on a continuous or near-continuous basis, and that communicate the resulting glucose data to a reader, receiver, or display device.
Product code QKQ has been used by FDA to classify a significant number of CGM systems currently on the U.S. market, including systems manufactured by several of the leading companies in the CGM space. The product code's breadth is sufficient to encompass CGM systems with varying sensor wear durations (from 7 days to 15 days or longer), different electrode chemistries (including both platinum-based and other metallic electrode systems), and different reader/transmitter form factors (including dedicated reader devices, smartphone-based reading systems, and hybrid approaches).
The assignment of product code QKQ to the Lumina CGM System is based on the following characteristics of the System that align with the product code definition:
• The C14 sensor is a subcutaneous electrode — it is inserted beneath the skin and resides in the subcutaneous tissue during the wear period.
• The C14 sensor measures glucose — it uses an enzymatic electrochemical mechanism to detect and quantify glucose in interstitial fluid.
• The C14 sensor operates as part of a continuous glucose monitoring system — it generates glucose measurements on a continuous basis (every 60 seconds) and transmits them to the R7 reader for processing and display.
Based on these characteristics, product code QKQ is the most specific and appropriate product code for the Lumina CGM System.
IV.B. Comparison with Other Potentially Applicable Product Codes
In determining that product code QKQ is the correct product code for the Lumina CGM System, we have considered and rejected the following alternative product codes that might, on a superficial reading, appear potentially applicable:
Product Code NBW — System, Test, Blood Glucose, Over the Counter. Product code NBW applies to blood glucose test strip reader systems — commonly referred to as blood glucose meters or glucometers — that use disposable test strips with a small blood sample to provide a single-point-in-time glucose measurement. This is the product code under which Solstice's prior product, the GlucoStrip RX-200, was cleared (510(k) No. K192847, cleared November 14, 2019). Product code NBW is not applicable to the Lumina CGM System because the Lumina system does not measure glucose from a fingerstick blood sample using disposable test strips. Rather, the Lumina system uses a subcutaneous implantable sensor to continuously measure glucose in interstitial fluid. The two technologies are fundamentally different in their mechanism of action, intended use, and clinical application. Accordingly, product code NBW is inapplicable, and the GlucoStrip RX-200 is not an appropriate predicate device for the Lumina CGM System.
Product Code OQN — Non-Invasive Glucose Monitoring Systems. Product code OQN encompasses glucose monitoring systems that measure glucose through non-invasive means — that is, without any component being inserted beneath the skin. Non-invasive glucose monitoring technologies include, for example, optical, spectroscopic, and transdermal approaches. Product code OQN is not applicable to the Lumina CGM System because the C14 sensor is a subcutaneous (minimally invasive) device that is physically inserted beneath the skin. The Lumina system is not a non-invasive device. The distinction between subcutaneous (minimally invasive) and non-invasive technologies is a well-established classification boundary, and FDA has consistently maintained separate product codes for these two categories of glucose monitoring devices.
Product Code MDS — Continuous Glucose Monitoring Systems for Adjunctive Use. Product code MDS was historically used to classify certain earlier-generation continuous glucose monitoring systems that were labeled for "adjunctive use" — meaning that the CGM data was intended to supplement, rather than replace, traditional fingerstick blood glucose measurements for diabetes management decisions. Over time, as CGM technology advanced and the clinical evidence base expanded, FDA's regulatory approach to CGM classification evolved. The March 2024 reclassification order effectively consolidated the regulatory treatment of CGM systems under 21 C.F.R. § 862.1355, and product code MDS has been largely subsumed into the QKQ classification framework. Product code MDS is not the appropriate product code for the Lumina CGM System; QKQ is the current and correct product code.
Conclusion. After evaluating each of the potentially applicable product codes, we conclude that product code QKQ is the correct and most specific product code for the Solstice Lumina™ CGM System. No alternative product code more accurately describes the System's technology, mechanism of action, or intended use.
IV.C. Predicate Device Product Code Alignment
A critical element of the product code analysis is confirming that the predicate devices upon which Solstice intends to rely for its substantial equivalence determination are classified under the same product code as the subject device. Alignment of product codes between the subject device and the predicate devices is not an absolute legal requirement — FDA may find substantial equivalence between devices classified under different product codes — but product code alignment significantly strengthens the substantial equivalence argument and reduces the risk of an FDA challenge to the classification determination.
Both of Solstice's identified predicate devices are classified under product code QKQ:
The alignment of both predicate devices under product code QKQ with the Lumina CGM System's anticipated QKQ classification provides robust support for Solstice's classification position. The fact that the secondary predicate (GlucoTrack NX-700) was cleared in March 2024, contemporaneously with the March 2024 reclassification order, is particularly significant because it demonstrates that FDA continued to apply product code QKQ to CGM systems under the updated classification framework established by the reclassification order.
We note that the detailed substantial equivalence analysis — including the comparison of intended use, technological characteristics, and the five key technological differences between the Lumina CGM System and the primary predicate — is addressed in the companion Regulatory Strategy Memorandum (1037-00002-Bramwell Grayson CPAs LLP) and is not reproduced in this memorandum.
V. REGULATION NUMBER ANALYSIS — 21 C.F.R. § 862.1355
V.A. Regulatory Text and Scope
The Lumina CGM System falls within the scope of the device classification regulation codified at 21 C.F.R. § 862.1355, which governs the "Glucose test system" classification. This regulation is part of Subchapter H (Medical Devices) of Title 21 of the Code of Federal Regulations and is located within Part 862 (Clinical Chemistry and Clinical Toxicology Devices), Subpart B (Clinical Chemistry Test Systems).
As originally codified, 21 C.F.R. § 862.1355 identified a "glucose test system" as a device intended to measure glucose quantitatively in blood and other body fluids. The regulation provided that such measurements aid in the diagnosis and treatment of carbohydrate metabolism disorders, including diabetes mellitus, neonatal hypoglycemia, and idiopathic hypoglycemia, as well as pancreatic islet cell carcinoma. The regulation originally contemplated primarily traditional laboratory-based and point-of-care glucose measurement systems.
As updated by the March 2024 reclassification order (discussed in detail in Section VII below), the regulatory text of 21 C.F.R. § 862.1355 now explicitly encompasses continuous glucose monitoring systems that use subcutaneous sensors to measure glucose in interstitial fluid on a continuous or near-continuous basis. The updated identification language reflects the technological evolution in glucose measurement from single-point-in-time blood glucose tests to continuous subcutaneous interstitial fluid glucose monitoring, and it clarifies that both categories of glucose measurement devices fall within the scope of this regulation number.
The Lumina CGM System falls squarely within the scope of 21 C.F.R. § 862.1355 as updated. The System is intended to measure glucose quantitatively in interstitial fluid (a body fluid) using a subcutaneous electrochemical sensor, for the purpose of aiding in the management and treatment of diabetes mellitus. The System's intended use — continuous monitoring of glucose levels to inform diabetes management decisions — is precisely the type of clinical application contemplated by the regulation.
V.B. Classification: Class II with Special Controls
Under 21 C.F.R. § 862.1355, as updated by the March 2024 reclassification order, continuous glucose monitoring systems with subcutaneous sensors are classified as Class II medical devices. The Class II classification means that:
1. General controls alone are insufficient. FDA has determined that general controls — the baseline regulatory requirements applicable to all medical devices, including establishment registration, device listing, good manufacturing practice requirements, labeling requirements, and medical device reporting — are by themselves insufficient to provide reasonable assurance of the safety and effectiveness of CGM devices.
2. Special controls are necessary. In addition to general controls, special controls are necessary to provide reasonable assurance of safety and effectiveness. Special controls may include performance standards, postmarket surveillance requirements, patient registries, special labeling requirements, and premarket data requirements, among others. The specific special controls applicable to CGM devices classified under product code QKQ are discussed in detail in Section VI below.
3. Premarket notification (510(k)) required. As a Class II device, the Lumina CGM System requires FDA clearance through the premarket notification (510(k)) process before it may be commercially distributed in the United States. Under the 510(k) process, Solstice must demonstrate that the Lumina CGM System is "substantially equivalent" to one or more legally marketed predicate devices — that is, that the Lumina system has the same intended use as the predicate device and either has the same technological characteristics or, if it has different technological characteristics, that those differences do not raise new questions of safety or effectiveness and that the device is at least as safe and effective as the predicate.
4. No PMA required. Because the Lumina CGM System is appropriately classified as Class II, a Premarket Approval Application ("PMA") — the more rigorous and costly premarket review pathway required for Class III devices — is not required. The Class II / 510(k) pathway represents a significantly less burdensome regulatory path than the PMA pathway, both in terms of the scope of data required and the anticipated FDA review timeline. This conclusion is subject to the condition that Solstice can successfully demonstrate substantial equivalence to a legally marketed predicate device. If substantial equivalence cannot be demonstrated, Solstice would need to consider alternative pathways, including the De Novo classification process. However, based on our analysis of the predicate devices and the Lumina CGM System's characteristics, we believe that substantial equivalence can be demonstrated, as discussed in the companion Regulatory Strategy Memorandum.
V.C. General Controls Applicable
As a Class II medical device, the Lumina CGM System is subject to the general controls applicable to all medical devices marketed in the United States under the Federal Food, Drug, and Cosmetic Act ("FDCA") and its implementing regulations. The key general controls applicable to the Lumina CGM System are summarized below:
Registration and Listing (21 C.F.R. Part 807). Solstice Biomedical Inc. (Delaware File No. 7834291), as the U.S. entity responsible for the commercial distribution of the Lumina CGM System in the United States, must register as a U.S. device establishment with FDA and list the Lumina CGM System in FDA's device listing database. Registration and listing must be completed prior to the commercial distribution of the device and must be updated annually. Solstice Ireland, as a foreign manufacturer, must also designate a U.S. agent and comply with foreign establishment registration requirements under 21 C.F.R. § 807.40.
Good Manufacturing Practice / Quality System Regulation (21 C.F.R. Part 820). The Lumina CGM System must be manufactured in compliance with FDA's Quality System Regulation ("QSR"), which establishes current good manufacturing practice ("cGMP") requirements for medical devices. The QSR encompasses requirements for design controls, document controls, purchasing controls, production and process controls, corrective and preventive actions ("CAPA"), and management responsibility, among others. We note that Solstice holds ISO 13485:2016 certification (certified by Meridian Conformity Assessment GmbH, Notified Body 0483), which provides a quality management system framework that substantially aligns with the QSR. However, certain U.S.-specific QSR requirements — including, for example, specific design control documentation requirements under 21 C.F.R. § 820.30 and management review requirements — must be separately addressed to ensure full QSR compliance. We recommend that Solstice conduct a gap analysis between its existing ISO 13485:2016-compliant quality management system and the requirements of 21 C.F.R. Part 820, and that any identified gaps be remediated prior to the 510(k) submission.
Labeling (21 C.F.R. Part 801). The Lumina CGM System must comply with FDA's labeling requirements, including requirements for adequate directions for use, the inclusion of required warnings and precautions, and compliance with the prescription device labeling requirements of 21 C.F.R. § 801.109. Labeling-specific special controls applicable to the Lumina CGM System are discussed in Section VI.H below.
Medical Device Reporting (21 C.F.R. Part 803). Solstice must comply with FDA's Medical Device Reporting ("MDR") requirements, which require manufacturers to report to FDA certain adverse events, including deaths, serious injuries, and malfunctions that could cause or contribute to a death or serious injury. Solstice should establish and maintain an MDR procedure specific to the U.S. market prior to commercial launch.
Premarket Notification (21 C.F.R. Part 807, Subpart E). As discussed above, a 510(k) premarket notification must be submitted to and cleared by FDA before the Lumina CGM System may be commercially distributed in the United States.
VI. SPECIAL CONTROLS APPLICABLE TO PRODUCT CODE QKQ
VI.A. Overview of Special Controls Framework
The special controls applicable to CGM devices classified under product code QKQ have been developed and refined over time through a combination of FDA guidance documents, reclassification orders, De Novo classification decisions, and the accumulated experience of FDA's review staff in evaluating CGM submissions. The special controls framework represents FDA's determination of the specific types of data and documentation — beyond the baseline general controls — that are necessary to provide reasonable assurance of the safety and effectiveness of CGM devices.
For the Lumina CGM System, the applicable special controls are those identified in FDA's reclassification order effective March 2024, as well as the relevant FDA guidance documents, including:
• "Integrated Continuous Glucose Monitoring Systems" (September 2023);
• "Self-Monitoring Blood Glucose Test Systems for Over-the-Counter Use" (as applicable to certain analytical performance requirements);
• "Cybersecurity in Medical Devices: Quality System Considerations and Content of Premarket Submissions" (September 2023);
• "Policy for Device Software Functions and Mobile Medical Applications" (updated September 2022); and
• "Content of Premarket Submissions for Device Software Functions" (updated November 2023).
This Section provides a detailed discussion of each category of special controls applicable to the Lumina CGM System. The companion iCGM Special Controls Memorandum (1037-00002-iCGM) provides additional analysis regarding the specific performance thresholds and additional special controls that would apply if the Lumina CGM System is designated as an iCGM.
VI.B. Analytical Performance Testing
Analytical performance testing is a core component of the special controls applicable to CGM devices. This testing is designed to demonstrate that the sensor and system meet defined performance criteria across the full measurement range and under the conditions of use for which the device is intended. The following categories of analytical performance testing are required for the Lumina CGM System:
Accuracy and Precision. Solstice must demonstrate that the C14 sensor provides accurate glucose measurements when compared to a reference glucose measurement method (e.g., a YSI laboratory glucose analyzer). The primary accuracy metric for CGM sensors is the Mean Absolute Relative Difference ("MARD"), which quantifies the average percentage difference between the sensor glucose readings and the reference glucose values. Solstice's internal target is an overall MARD of ≤ 9.0%, which is consistent with the performance levels achieved by currently marketed CGM systems classified under product code QKQ, including the predicate devices. MARD should be evaluated across multiple glucose ranges (hypoglycemic, euglycemic, and hyperglycemic ranges) and across the full 14-day sensor wear period, with particular attention to whether sensor accuracy degrades over the life of the sensor.
Consensus Error Grid Analysis. Solstice must demonstrate that a high proportion of paired data points (sensor glucose value paired with reference glucose value) fall within clinically acceptable zones of the Clarke Error Grid (or the Consensus Error Grid, which is the updated version of the Clarke Error Grid). The performance target is that ≥ 99% of paired data points fall within Zones A and B of the Clarke Error Grid. Zone A represents glucose values within ±20% of the reference value (or within ±20 mg/dL for reference values < 70 mg/dL), while Zone B represents values that are outside of Zone A but would not lead to inappropriate treatment decisions. Data points falling in Zones C, D, or E represent clinically significant inaccuracies that could lead to inappropriate clinical decisions. Achieving ≥ 99% of paired data points in Zones A and B is a well-established performance benchmark for CGM systems.
Linearity. Solstice must demonstrate that the sensor response is linear across the claimed measurement range of 40–400 mg/dL (2.2–22.2 mmol/L). Linearity testing should be performed using glucose solutions spanning the full measurement range, and the results should demonstrate that the sensor output is proportional to the glucose concentration within acceptable limits. Any deviations from linearity at the extremes of the measurement range should be characterized and documented.
Interference Testing. Solstice must assess the potential for common endogenous and exogenous substances to interfere with the sensor's glucose measurements. The interference testing program should evaluate, at a minimum, the following substances known or suspected to interfere with electrochemical glucose sensors:
• Acetaminophen (paracetamol) — a well-known interferent for electrochemical glucose sensors, particularly at therapeutic and supratherapeutic concentrations;
• Ascorbic acid (vitamin C);
• Uric acid;
• Salicylic acid;
• Dopamine;
• Maltose and other sugars that may cross-react with glucose oxidase-based sensors;
• Hydroxyurea; and
• Other substances identified through a systematic risk assessment based on the sensor's specific chemistry and electrode coating.
The interference testing program should be designed and executed in accordance with CLSI EP07-A3 or equivalent methodology, and the results should be presented in the 510(k) submission with clear identification of any substances that produce clinically significant interference.
Sensor-to-Sensor Precision and Lot-to-Lot Variability. Solstice must demonstrate that the C14 sensor performs consistently across individual sensor units and across different manufacturing lots. This testing should include evaluation of sensor-to-sensor precision (the variability in glucose readings obtained from different sensor units inserted simultaneously or sequentially in the same subject) and lot-to-lot variability (the variability in performance across sensors manufactured in different production lots). Acceptable precision and lot-to-lot variability levels should be defined based on the established performance of the predicate devices and current FDA expectations.
Warm-Up Time Characterization. Solstice must characterize the sensor warm-up period — the time from sensor insertion to the generation of the first accurate glucose reading. Solstice's target warm-up time is ≤ 60 minutes, which is competitive with currently marketed CGM systems. The warm-up time characterization study should demonstrate that glucose readings generated after the claimed warm-up period meet the System's stated accuracy specifications.
Sensor Functional Life Demonstration. Solstice must demonstrate that the C14 sensor maintains acceptable performance throughout the full claimed 14-day (336-hour) wear period. This should include evaluation of sensor accuracy (MARD), precision, and signal stability over the entire sensor life, with particular attention to any degradation in performance during the final days of the wear period. Sensor end-of-life behavior (e.g., signal dropout, increased noise, or accuracy degradation) should be characterized and documented.
VI.C. Clinical Performance Testing
In addition to bench-level analytical performance testing, FDA requires clinical study data demonstrating the performance of the CGM system in a representative population of intended users under real-world conditions of use. Clinical performance testing is a critical element of the special controls for CGM devices classified under product code QKQ.
Solstice has designed the LUMINA-US clinical study (Protocol No. SBD-LUM-CL-001) to address these clinical performance requirements. The key parameters of the LUMINA-US study are as follows:
The LUMINA-US study has been designed to generate the clinical data necessary to support the 510(k) submission, including system-level accuracy data (MARD), Clarke Error Grid analysis, and evaluation of sensor performance over the full 14-day wear period. The study population includes both Type 1 and Type 2 diabetes patients to demonstrate the System's performance across the full spectrum of the intended use population. The study design and protocol have been developed in consultation with Pinnacle Regulatory Consulting Group LLC (Dr. Sandra Ellison and Thomas Greenbaum) and are intended to be consistent with FDA expectations as articulated in FDA guidance documents and as reflected in the clinical data packages submitted for the predicate devices.
In addition to the clinical accuracy study, FDA's special controls for CGM devices typically require a labeling comprehension study to demonstrate that intended users can correctly interpret the device's output — including glucose values, trend arrows, alerts, and error messages — and can correctly perform essential device functions (e.g., sensor insertion, reader operation, and alert configuration). Solstice should plan for a labeling comprehension study as a component of the overall clinical data package.
VI.D. Biocompatibility. The Lumina CGM System includes components that come into direct or indirect contact with the patient's body, and biocompatibility testing is required to demonstrate that these patient-contacting components do not pose unacceptable risks of adverse biological responses. Biocompatibility testing must be conducted in accordance with ISO 10993-1:2018 ("Biological evaluation of medical devices — Part 1: Evaluation and review within a risk management process") and the relevant parts of the ISO 10993 series.
The biocompatibility testing requirements differ for the C14 sensor and the R7 reader based on the nature and duration of their patient contact:
Lumina C14 Sensor (Subcutaneous, Limited Contact >24 hours to 30 days). The C14 sensor is a subcutaneously implanted device with a maximum wear duration of 14 days (336 hours), placing it in the "limited contact" category (>24 hours to 30 days) for body contact with subcutaneous tissue. Under ISO 10993-1:2018, the following biocompatibility endpoints must be evaluated for the C14 sensor:
• Cytotoxicity (ISO 10993-5)
• Sensitization (ISO 10993-10)
• Irritation (ISO 10993-23 or equivalent)
• Acute systemic toxicity (ISO 10993-11)
• Subchronic toxicity (ISO 10993-11)
• Implantation (ISO 10993-6)
• Hemocompatibility (ISO 10993-4)
• Genotoxicity (ISO 10993-3)
This represents a comprehensive biocompatibility evaluation panel reflecting the invasive nature of the C14 sensor and its extended subcutaneous contact duration.
Lumina R7 Reader (Skin Contact, Limited Contact). The R7 reader is a wearable device that contacts the intact skin surface of the upper arm. Under ISO 10993-1:2018, the biocompatibility evaluation for a device with intact skin surface contact requires assessment of the following endpoints:
• Cytotoxicity (ISO 10993-5)
• Sensitization (ISO 10993-10)
• Irritation (ISO 10993-23 or equivalent)
The biocompatibility testing for both the C14 sensor and the R7 reader has been contracted to Whitmore Laboratories Inc. (A2LA Accreditation Certificate No. 3847.01), a GLP-compliant contract testing laboratory with extensive experience in medical device biocompatibility testing. The target completion date for all biocompatibility testing is August 31, 2025, and the total budget for biocompatibility testing is $485,000.
We note that certain biocompatibility studies may have been conducted during the development and EU MDR CE marking process for the Lumina CGM System. To the extent that existing biocompatibility data generated under ISO 10993 methodology is available and scientifically valid, Solstice should evaluate whether those data can be leveraged for the 510(k) submission, subject to FDA's acceptance of the data and any additional U.S.-specific requirements. The leverageability of existing EU data is discussed further in Section IX below.
VI.E. Electromagnetic Compatibility (EMC) and Electrical Safety
The R7 reader/transmitter is an active electronic medical device that incorporates wireless communication functionality (BLE 5.2). As such, it is subject to electromagnetic compatibility and electrical safety testing requirements as part of the special controls for product code QKQ.
Electromagnetic Compatibility (EMC). EMC testing must be performed in accordance with 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"). EMC testing encompasses both emissions testing (demonstrating that the R7 reader does not emit electromagnetic interference at levels that could disrupt the operation of other electronic devices) and immunity testing (demonstrating that the R7 reader continues to operate safely and effectively in the presence of external electromagnetic fields and disturbances that may be encountered in the intended use environment).
BLE 5.2 Wireless Coexistence Testing. Because the Lumina CGM System utilizes BLE 5.2 for wireless communication between the C14 sensor and the R7 reader, and between the R7 reader and the Lumina Mobile App, wireless coexistence testing must be performed to demonstrate that the BLE 5.2 communication links are robust and reliable in the presence of other wireless devices and signals (e.g., Wi-Fi, other Bluetooth devices) that may be present in the user's environment. Coexistence testing should assess whether the presence of other wireless signals can cause clinically significant delays in data transmission, data loss, or alert latency increases beyond the specified ≤ 5-minute threshold.
Electrical Safety. Electrical safety testing must be performed in accordance with IEC 60601-1 ("Medical electrical equipment — Part 1: General requirements for basic safety and essential performance"). This testing evaluates the safety of the R7 reader's electrical design, including protection against electric shock, thermal hazards, and mechanical hazards.
All EMC and electrical safety testing has been contracted to Whitmore Laboratories Inc., with a total budget of $175,000. Testing is expected to be coordinated with the biocompatibility testing timeline to ensure that all laboratory-based testing is completed in advance of the 510(k) submission.
VI.F. Software Validation and Verification
The Lumina CGM System incorporates multiple software components that are integral to its function and that directly affect the safety and effectiveness of the device. Software verification and validation ("V&V") is a critical special control for CGM devices, and FDA expects comprehensive software documentation in the 510(k) submission.
Software Level of Concern. Based on the classification framework set forth in FDA guidance "Content of Premarket Submissions for Device Software Functions" (updated November 2023), the software components of the Lumina CGM System are classified as "Major" level of concern. This classification reflects the fact that the software is used to generate glucose values and alerts that directly inform clinical decisions regarding insulin dosing and diabetes management, and that a software failure or erroneous output could lead to incorrect treatment decisions with the potential for serious injury (e.g., hypoglycemia or hyperglycemia).
Compliance with IEC 62304. The software lifecycle for all Lumina CGM software components must comply with IEC 62304:2006/A1:2015 ("Medical device software — Software life cycle processes"). This standard establishes the processes, activities, and tasks required for the development and maintenance of medical device software, including software development planning, software requirements analysis, software architectural design, software detailed design, software unit implementation, software integration and integration testing, software system testing, and software release.
Software Components Requiring V&V Documentation. The following software components must be covered by comprehensive V&V documentation in the 510(k) submission:
• Lumina Firmware v3.4.2 — the embedded firmware running on the C14 sensor's microprocessor, controlling sensor operation, signal acquisition, raw data processing, and BLE data transmission to the R7 reader;
• Lumina Reader OS v2.1.0 — the operating system and application software running on the R7 reader, controlling data reception, display rendering, alert generation, and BLE communication with the Lumina Mobile App;
• LuminaPredict Algorithm v2.1 — the proprietary glucose prediction algorithm that processes raw sensor signals and generates the calibrated glucose values, trend arrows, and rate-of-change calculations displayed to the user; and
• Lumina Mobile App v1.0.3 — the companion mobile application for iOS and Android platforms, providing supplementary data display, historical data review, data sharing, and cloud connectivity.
Algorithm Validation. The LuminaPredict Algorithm v2.1 is a critical software component that directly determines the glucose values displayed to the user. FDA expects detailed documentation of the algorithm's design, development, verification, and validation, including demonstration that the algorithm performs within the specified accuracy requirements (i.e., that the algorithm-generated glucose values achieve the target MARD when compared to reference glucose values). Algorithm validation should include evaluation of algorithm performance across the full measurement range (40–400 mg/dL), across different glucose rate-of-change conditions (stable, rising, falling), and throughout the full 14-day sensor wear period. Any calibration algorithms (if applicable), signal filtering algorithms, and error detection algorithms incorporated into LuminaPredict should also be documented and validated.
VI.G. Cybersecurity. The Lumina CGM System incorporates wireless communication capabilities and connectivity to external devices (smartphones), which creates potential cybersecurity risks that must be addressed as part of the special controls. FDA's guidance document "Cybersecurity in Medical Devices: Quality System Considerations and Content of Premarket Submissions" (September 2023) establishes the framework for cybersecurity documentation that FDA expects in premarket submissions for connected medical devices.
The following cybersecurity documentation and testing are required for the Lumina CGM System:
Software Bill of Materials (SBOM). Solstice must provide a comprehensive SBOM identifying all software components, including third-party software components, open-source software components, and proprietary software components, along with their version numbers, suppliers, and known vulnerabilities. The SBOM must cover all software components of the Lumina CGM System, including the Lumina Firmware, Lumina Reader OS, LuminaPredict Algorithm, Lumina Mobile App, and any underlying operating system or middleware components.
Threat Modeling. Solstice must conduct and document a cybersecurity threat model identifying the potential threats to the Lumina CGM System's security. Solstice has completed an initial threat model using the STRIDE (Spoofing, Tampering, Repudiation, Information Disclosure, Denial of Service, Elevation of Privilege) framework. The threat model should identify and assess threats to the BLE 5.2 communication link between the C14 sensor and the R7 reader, the BLE communication link between the R7 reader and the Lumina Mobile App, the data stored on the R7 reader and the Lumina Mobile App, and any cloud-based data storage and communication pathways.
Vulnerability Assessment. Solstice must conduct a vulnerability assessment to identify and evaluate potential security vulnerabilities in the System's hardware, software, and communication protocols. The vulnerability assessment should be documented and should include an assessment of the severity and exploitability of each identified vulnerability, along with the mitigations implemented to address each vulnerability.
Software Update and Patch Management Plan. Solstice must develop and document a plan for managing software updates and security patches over the commercial life of the Lumina CGM System. The plan should address the process for identifying, developing, validating, and deploying software updates and patches, including both planned updates (e.g., feature enhancements, performance improvements) and unplanned updates (e.g., security patches in response to newly discovered vulnerabilities).
Authentication and Encryption Protocols. Solstice must document the authentication and encryption protocols used to secure the BLE 5.2 communication links and the mobile application communications. The documentation should demonstrate that appropriate cryptographic protections are in place to prevent unauthorized access to patient health data and to ensure the integrity of glucose data transmitted between device components.
VI.H. Labeling. The labeling for the Lumina CGM System must comply with the general labeling requirements of 21 C.F.R. Part 801 as well as the specific labeling-related special controls applicable to CGM devices classified under product code QKQ. Key labeling requirements include:
Adequate Directions for Use and Warnings. The labeling must include complete and adequate directions for use, including instructions for sensor insertion using the Lumina Inserter, sensor removal and disposal, R7 reader operation and charging, system pairing and setup, glucose display interpretation (including trend arrows and trend graphs), alert configuration and management, sensor warm-up period instructions, and device limitations. The labeling must also include appropriate warnings and precautions, including, for example, warnings regarding the sensor warm-up period (during which glucose readings may not be accurate), warnings regarding potential interferents, warnings regarding the need for confirmatory fingerstick blood glucose measurements in certain clinical situations, and warnings regarding device use in specific patient populations or clinical settings.
Sensor Insertion and Calibration Instructions. The labeling must provide clear, step-by-step instructions for sensor insertion, including illustrations or photographs demonstrating proper insertion technique. If the Lumina CGM System requires periodic fingerstick calibration during the sensor wear period, the calibration procedure must be clearly described in the labeling. If the system is designed as a "factory-calibrated" or "zero-calibration" system, the labeling must clearly state that no user calibration is required.
Alert Configuration Instructions. The labeling must explain how to configure the System's hypoglycemia and hyperglycemia alerts, including how to adjust alert thresholds, how to enable or disable specific alert types, and how to distinguish between different alert types (e.g., audible alerts, vibratory alerts).
Device Limitations. The labeling must clearly identify the limitations of the device, including the measurement range (40–400 mg/dL), the sensor wear duration (14 days), the intended user population (adults aged 18 and older with Type 1 or Type 2 diabetes mellitus), and any conditions or circumstances under which the device should not be used or under which device accuracy may be affected.
Prescription Use Designation. The labeling must identify that the Lumina CGM System is intended for prescription use only, in accordance with 21 C.F.R. § 801.109. The device is not intended for over-the-counter sale or use without the supervision of a healthcare professional.
VII. FDA RECLASSIFICATION ORDER EFFECTIVE MARCH 2024
VII.A. Background and Purpose of the Reclassification Order
FDA issued a reclassification order effective March 2024 that updated the classification framework for glucose test systems classified under 21 C.F.R. § 862.1355. This reclassification order was the culmination of a multi-year effort by FDA to modernize and rationalize the regulatory classification of glucose monitoring devices in light of the significant technological advances that have occurred in the CGM field over the past decade.
The technological landscape for glucose monitoring has evolved dramatically since the original codification of 21 C.F.R. § 862.1355. When the regulation was first promulgated, glucose test systems were predominantly laboratory-based analyzers and point-of-care blood glucose meters. The advent of CGM technology — and the subsequent evolution from first-generation CGM systems (which required frequent fingerstick calibrations and were labeled for adjunctive use only) to current-generation CGM systems (which offer longer sensor wear periods, factory calibration, integrated predictive algorithms, and increasing use as primary glucose monitoring tools) — created a growing need to update the regulatory framework to reflect the current state of the technology.
The March 2024 reclassification order addressed this need by consolidating and clarifying the regulatory treatment of CGM systems. The order was informed by FDA's experience in reviewing CGM submissions over the preceding years, including De Novo classification decisions for iCGM devices, and by input received from stakeholders during public comment periods.
VII.B. Key Changes Introduced by the Reclassification Order
The March 2024 reclassification order introduced several key changes to the classification framework for glucose test systems under 21 C.F.R. § 862.1355:
Updated Device Identification Language. The reclassification order updated the device identification language under 21 C.F.R. § 862.1355 to explicitly encompass continuous glucose monitoring systems that use subcutaneous sensors to measure glucose in interstitial fluid. Prior to the reclassification order, the regulatory text focused primarily on glucose test systems that measure glucose in blood and did not explicitly reference CGM systems or interstitial fluid measurement. The updated identification language eliminates any ambiguity regarding the applicability of 21 C.F.R. § 862.1355 to CGM systems of the type represented by the Lumina CGM System.
Clarification and Codification of Special Controls. The reclassification order clarified and codified the special controls applicable to CGM devices. Prior to the order, many of the special controls applicable to CGM devices were articulated through FDA guidance documents and individual De Novo classification decisions, rather than through the regulatory text itself. The reclassification order consolidated these requirements into a single, coherent set of special controls, providing manufacturers with greater clarity and predictability regarding the regulatory expectations for CGM submissions.
Alignment with Current Performance Expectations. The reclassification order aligned the special controls with current performance expectations for CGM devices, including expectations regarding MARD thresholds, error grid requirements, sensor wear duration characterization, software validation, and cybersecurity. These updated performance expectations are consistent with the requirements articulated in FDA's September 2023 guidance document "Integrated Continuous Glucose Monitoring Systems." The alignment of the codified special controls with the September 2023 iCGM guidance provides a clear and unified regulatory framework for CGM submissions.
Streamlined Regulatory Pathway. The reclassification order confirmed that the Class II classification with