PRIVILEGED AND CONFIDENTIAL ATTORNEY-CLIENT COMMUNICATION / ATTORNEY WORK PRODUCT
MEMORANDUM
TO: Dr. Niamh Tierney, VP of Regulatory Affairs, Solstice Biomedical Devices Ltd. Marcus Hale, VP of U.S. Operations, Solstice Biomedical Inc.
FROM: Miriam Calloway, Partner, Calderwood & Harkness LLP Amy Whitfield, Associate, Calderwood & Harkness LLP
DATE: May 12, 2025
RE: Analysis of Investigational Device Exemption (IDE) Exemption Applicability Under 21 C.F.R. § 812.2(c)(3) for LUMINA-US Clinical Study (Protocol SBD-LUM-CL-001)
Engagement Reference No.: 1037-00002
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I. Executive Summary
The purpose of this memorandum is to analyze whether the planned LUMINA-US clinical study (Protocol SBD-LUM-CL-001) qualifies for the Investigational Device Exemption ("IDE") exemption under 21 C.F.R. § 812.2(c)(3) as a non-significant risk ("NSR") diagnostic device study, thereby avoiding the need for FDA IDE application approval prior to commencing the study. This analysis was undertaken at the request of Solstice Biomedical Devices Ltd. ("Solstice" or the "Company") following the opening of this engagement on April 22, 2025.
The investigational product at issue is the Solstice Lumina™ CGM System, which comprises two principal components: (1) the Lumina C14, a subcutaneously implantable continuous glucose monitoring ("CGM") sensor with a 14-day wear duration, and (2) the Lumina R7, a wearable reader/transmitter device. Together, these components constitute an investigational Class II medical device intended for continuous glucose monitoring in persons aged 18 and older with Type 1 or Type 2 diabetes mellitus.
The LUMINA-US study is a prospective, single-arm, multicenter clinical study designed to evaluate sensor accuracy, as measured by Mean Absolute Relative Difference ("MARD"), safety, and user labeling comprehension across a total of 350 subjects (175 with Type 1 diabetes mellitus and 175 with Type 2 diabetes mellitus) enrolled at six U.S. clinical sites. The study will be managed by Veltrano Clinical Research Organization Inc. ("Veltrano CRO"), and Institutional Review Board ("IRB") oversight will be provided by Clearwater Institutional Review Board LLC ("Clearwater IRB") (IRB Registration No. IRB-2019-04821).
Based on the analysis set forth below, Calderwood & Harkness LLP ("Calderwood & Harkness" or "we") concludes that the LUMINA-US study likely qualifies for treatment as an NSR study under the abbreviated IDE framework of 21 C.F.R. § 812.2(b). Although the strict diagnostic device exemption under § 812.2(c)(3) may not fully apply to this study — owing to the invasive nature of the Lumina C14 sensor and its introduction of low-level energy into the subject — the study presents a non-significant risk profile that permits it to proceed under IRB oversight without submission of a full IDE application to the U.S. Food and Drug Administration ("FDA").
However, given certain features of the Lumina C14 sensor — in particular, subcutaneous implantation for a 14-day wear period and the novel PtIr-4G electrode coating — we strongly recommend that Solstice confirm this determination with FDA through the Pre-Submission ("Pre-Sub") meeting currently scheduled for August 14, 2025. Including a specific question regarding IDE exemption applicability in the Pre-Sub meeting package will provide a measure of regulatory certainty prior to the planned study commencement date of September 15, 2025, and will significantly mitigate the risk of a subsequent FDA disagreement with the NSR determination.
This memorandum addresses the applicable regulatory framework in detail, applies that framework to the facts of the LUMINA-US study, compares the study to precedent FDA determinations for analogous CGM clinical investigations, identifies remaining risk factors, and sets forth our recommendations and proposed next steps.
II. Background
A. The Solstice Lumina™ CGM System
The Solstice Lumina™ CGM System ("Lumina CGM System" or the "System") is a next-generation continuous glucose monitoring system designed, developed, and manufactured by Solstice Biomedical Devices Ltd., a company incorporated and headquartered in Galway, Ireland, with U.S. operations conducted through its wholly owned subsidiary, Solstice Biomedical Inc., located in San Diego, California.
The System comprises two principal hardware components and associated software:
Lumina C14 Sensor. The Lumina C14 is a subcutaneously insertable continuous glucose monitoring sensor designed for a 14-day (336-hour) wear duration. The sensor utilizes Solstice's fourth-generation enzymatic electrochemical biosensor technology featuring a proprietary platinum-iridium electrode coating, designated as PtIr-4G technology. The C14 sensor is inserted into the subcutaneous tissue of the abdomen or the posterior aspect of the upper arm using a proprietary minimally invasive insertion device (the Lumina Applicator). Once inserted, the sensor continuously measures interstitial glucose concentrations through an enzymatic electrochemical reaction at the working electrode and transmits real-time glucose data wirelessly to the Lumina R7 reader/transmitter via Bluetooth Low Energy ("BLE") 5.2 protocol. The sensor's measurement range spans 40 to 400 mg/dL, with a warm-up time of no greater than 60 minutes following insertion. The sensor operates using Lumina Firmware v3.4.2.
Lumina R7 Reader/Transmitter. The Lumina R7 is a wearable reader/transmitter device designed to be worn on the upper arm. The R7 receives BLE data from the subcutaneously inserted C14 sensor and displays real-time glucose values, trend arrows indicating the direction and rate of glucose change, and 8-hour trend graphs. The R7 features configurable hypo- and hyperglycemia alert thresholds with an alert latency of no greater than 5 minutes. The R7 communicates data to the Solstice Lumina™ mobile application, which is available on both iOS and Android platforms. The R7 operates using Lumina Reader OS v2.1.0.
Software Components. In addition to the firmware and operating system noted above, the System incorporates the LuminaPredict Algorithm v2.1, a proprietary glucose prediction algorithm designed to provide predictive glucose alerts, and the Lumina Mobile App v1.0.3, which enables remote data viewing, data sharing with healthcare providers, and historical data analysis.
Regulatory Classification. The Lumina CGM System's anticipated product code is QKQ (Electrode, Glucose, Subcutaneous), and the System is anticipated to be classified as a Class II medical device under 21 C.F.R. § 862.1355. The System is currently CE-marked in the European Union under the EU Medical Device Regulation (EU MDR), pursuant to EU MDR Certificate No. MCA-2024-07319, issued on September 12, 2024, by Meridian Conformity Assessment GmbH (Notified Body 0483). The Lumina CGM System has been commercially available in the European Union since September 2024.
U.S. Regulatory Strategy. Solstice intends to submit a traditional 510(k) premarket notification covering both the C14 sensor and R7 reader/transmitter as a complete system. The target 510(k) submission date is April 30, 2026, with a target FDA clearance date in the third quarter of 2026. The primary predicate device for the 510(k) submission is the NovaSense GlucoTrack NX-500 (510(k) No. K211034, cleared June 18, 2022), and the secondary predicate device is the NovaSense GlucoTrack NX-700 (510(k) No. K230489, cleared March 7, 2024). Solstice has prior FDA clearance history for the GlucoStrip RX-200 Test Strip Reader (510(k) No. K192847, cleared November 14, 2019), establishing the Company's familiarity with FDA's premarket review processes.
B. The LUMINA-US Clinical Study (Protocol SBD-LUM-CL-001)
The LUMINA-US study is a prospective, single-arm, multicenter clinical investigation designed to generate the clinical performance and safety data necessary to support Solstice's 510(k) submission and potential integrated continuous glucose monitoring ("iCGM") classification of the Lumina CGM System.
Study Design and Objectives. The study is designated Protocol SBD-LUM-CL-001, with the study title "LUMINA-US." It is designed as a prospective, single-arm, multicenter clinical study evaluating the performance of the Lumina CGM System in adult subjects with diabetes mellitus.
Study Population. The study will enroll a total of 350 subjects, equally divided between 175 subjects with Type 1 diabetes mellitus and 175 subjects with Type 2 diabetes mellitus. All subjects must be adults aged 18 years and older. Subjects will be enrolled across six U.S. clinical sites, the locations and principal investigators for which are being finalized.
Primary Endpoint. The primary endpoint of the LUMINA-US study is sensor accuracy as measured by Mean Absolute Relative Difference (MARD), with a target of MARD ≤ 9.0%. Additionally, the study will evaluate Consensus Error Grid performance, with a target of ≥ 99% of paired data points falling within Zones A and B of the Clarke Error Grid Analysis.
Secondary Endpoints. Secondary endpoints include safety (assessed through reporting and analysis of adverse events, device-related adverse events, and sensor insertion site reactions) and user labeling comprehension (assessed through labeling comprehension questionnaires administered to study participants).
Study Duration. The overall study duration is projected to be approximately six months, comprising approximately 14 weeks of enrollment, a 14-day sensor wear period per subject, and approximately 8 weeks of data analysis following the conclusion of enrollment. The target study commencement date is September 15, 2025, with a target study completion date of March 15, 2026.
Contract Research Organization. Veltrano Clinical Research Organization Inc. ("Veltrano CRO") has been selected to manage the clinical study. Veltrano CRO is located at 500 North Capitol Street, Suite 700, Indianapolis, Indiana 46204, and the key contact is Dr. Lisa Fontaine, VP of Clinical Operations. Veltrano CRO will be responsible for site management, monitoring, data management, and related clinical operations activities under a master services agreement currently under negotiation.
Institutional Review Board. IRB oversight for the LUMINA-US study will be provided by Clearwater Institutional Review Board LLC, located at 3200 Bayshore Boulevard, Tampa, Florida 33629 (IRB Registration No. IRB-2019-04821). Clearwater IRB will serve as the single reviewing IRB for all six clinical sites.
Budget. The clinical study budget is estimated at $4,200,000, based on 350 subjects at a per-subject cost of approximately $12,000.
Intended Use of Study Data. The data generated by the LUMINA-US study is designed to support the 510(k) submission and potential iCGM special controls classification of the Lumina CGM System.
C. Purpose of This Analysis
Solstice must determine, prior to commencing the LUMINA-US study, whether an approved Investigational Device Exemption is required from FDA before the study may lawfully begin, or whether the study falls within one of the IDE exemptions that would permit the study to proceed under IRB oversight without a separate FDA submission.
The resolution of this question has significant implications for Solstice's regulatory timeline. If the LUMINA-US study qualifies as either an exempt diagnostic device study under 21 C.F.R. § 812.2(c)(3) or, alternatively, as a non-significant risk device study under the abbreviated IDE framework of 21 C.F.R. § 812.2(b), the study may proceed upon IRB approval without the need for an FDA IDE application. This would significantly streamline the regulatory pathway, preserve the September 15, 2025 target study start date, and maintain alignment with downstream milestones, including the 510(k) submission target of April 30, 2026 and the FDA clearance target of Q3 2026.
Conversely, if the LUMINA-US study is determined to involve a significant risk device — either by the reviewing IRB or by FDA — a full IDE application would be required, which would introduce additional regulatory complexity and likely delay the study start by several months.
This analysis has been prepared to provide Solstice with a thorough assessment of IDE exemption applicability and to inform the Company's regulatory strategy. Additionally, this analysis is being prepared in anticipation of the Pre-Submission meeting with FDA's Center for Devices and Radiological Health ("CDRH"), specifically the Office of Health Technology 2, Division of Chemistry and Toxicology Devices ("OHT2-DCT"), which is currently scheduled for August 14, 2025. Solstice intends to include a question in the Pre-Sub meeting package confirming the IDE exemption applicability and the appropriateness of proceeding under the NSR abbreviated IDE pathway.
III. Legal Framework: IDE Requirements and Exemptions
A. Overview of IDE Regulations (21 C.F.R. Part 812)
The Investigational Device Exemption regulations, codified at 21 C.F.R. Part 812, govern the conduct of clinical investigations of medical devices intended for human use. The statutory basis for these regulations is found in Section 520(g) of the Federal Food, Drug, and Cosmetic Act ("FD&C Act"), 21 U.S.C. § 360j(g), which authorizes FDA to establish by regulation the conditions under which investigational devices may be used in clinical studies.
Section 812.1 of the IDE regulations sets forth the purpose and scope of Part 812, stating that the regulations are designed "to encourage, to the extent consistent with the protection of the public health and safety and with ethical standards, the discovery and development of useful devices intended for human use." The regulations accomplish this purpose by establishing a framework under which investigational devices may be studied in human subjects while ensuring that adequate safeguards are in place to protect the health, safety, and welfare of study participants.
As a general matter, any clinical investigation of a device — that is, any study involving one or more subjects to determine the safety or effectiveness of a device — must have an approved IDE or qualify for an exemption from the IDE requirements before it may lawfully be conducted in the United States. See 21 U.S.C. § 360j(g); 21 C.F.R. § 812.1. The scope of this requirement is broad: it applies to investigations of devices that are subject to premarket approval ("PMA"), premarket notification (510(k)), or De Novo classification, unless a specific exemption applies.
The IDE regulations distinguish between two categories of investigational device studies, each subject to different levels of regulatory oversight:
Significant Risk (SR) Device Studies. Under 21 C.F.R. § 812.2(a), investigations involving devices that present a significant risk to the health, safety, or welfare of study subjects are subject to the full IDE requirements. For such studies, the sponsor must submit a complete IDE application to FDA in accordance with 21 C.F.R. § 812.20, and the study may not commence until FDA has approved the IDE application. The IDE application must include, among other things, a complete investigational plan, a description of the investigational device and its manufacturing process, a comprehensive risk analysis, informed consent documents, IRB approval, and information regarding prior investigations of the device. FDA has 30 days from receipt of the IDE application to review it and issue a decision, although this timeline may be extended if FDA requests additional information.
Non-Significant Risk (NSR) Device Studies. Under 21 C.F.R. § 812.2(b), investigations involving devices that do not present a significant risk to study subjects are subject to abbreviated IDE requirements. For NSR studies, the sponsor is not required to submit an IDE application to FDA. Instead, the sponsor must comply with certain specified provisions of Part 812, including requirements for informed consent (21 C.F.R. Part 50), IRB review and approval (21 C.F.R. Part 56), device labeling (21 C.F.R. § 812.5), monitoring (21 C.F.R. § 812.46), and recordkeeping and reporting (21 C.F.R. §§ 812.140, 812.150). The primary oversight responsibility for NSR studies rests with the reviewing IRB rather than with FDA, although FDA retains the authority to review and disagree with an NSR determination at any time.
B. The Diagnostic Device Exemption — 21 C.F.R. § 812.2(c)(3)
In addition to the SR/NSR framework, the IDE regulations provide several categorical exemptions from IDE requirements for certain types of investigations. Among these, 21 C.F.R. § 812.2(c)(3) exempts investigations of diagnostic devices from the full scope of IDE requirements — including both the full IDE requirements for SR devices and the abbreviated IDE requirements for NSR devices — provided that certain conditions are met.
The diagnostic device exemption under § 812.2(c)(3) is a significant provision for companies developing in vitro diagnostic and other diagnostic products because, when applicable, it effectively permits clinical investigations to proceed with no IDE-related FDA submission and minimal IDE-specific regulatory burden beyond standard IRB oversight and good clinical practice.
The conditions for the § 812.2(c)(3) exemption are as follows:
1. The device is being tested in compliance with applicable provisions of 21 C.F.R. Part 809 (in vitro diagnostic products for human use), if applicable to the particular device or investigation;
2. The testing is noninvasive, or if the device is invasive, the investigation does not by its nature present a significant risk to the subject beyond the risks inherent in the diagnostic procedure itself;
3. The testing does not require an invasive sampling procedure that presents a significant risk to the subject;
4. The testing does not, by design or intention, introduce energy into a subject; and
5. The testing is not used as a diagnostic procedure without confirmation of the diagnosis by another medically established diagnostic product or procedure.
The critical nuance of § 812.2(c)(3) lies in the interplay between the "noninvasive" condition and the "energy introduction" condition. The provision was principally designed to address in vitro diagnostic testing, where a specimen has been collected from a patient and is tested outside the body, or noninvasive diagnostic procedures that do not involve insertion of a device into the body or the introduction of energy. When a diagnostic device is invasive — as in the case of a subcutaneously inserted sensor — and introduces energy into the subject — as in the case of an electrochemical sensor with wireless data transmission — the strict applicability of the § 812.2(c)(3) exemption becomes questionable.
This tension is directly relevant to the LUMINA-US study, as the Lumina C14 sensor is both invasive (subcutaneously inserted) and introduces energy (electrochemical sensing current and BLE 5.2 radio frequency transmission). These features complicate the direct application of the § 812.2(c)(3) exemption and, as discussed in greater detail below, necessitate analysis under the alternative NSR abbreviated IDE framework.
C. Significant Risk vs. Non-Significant Risk Device Determination
Central to the IDE regulatory framework is the distinction between significant risk and non-significant risk devices. This determination directly affects the level of regulatory oversight applicable to a clinical investigation and is therefore one of the most consequential threshold questions in the planning of any U.S. device clinical study.
Definition of Significant Risk Device. A "significant risk device" is defined at 21 C.F.R. § 812.3(m) as a device that:
(i) Is intended as an implant and presents a potential for serious risk to the health, safety, or welfare of a subject;
(ii) Is purported or represented to be for a use in supporting or sustaining human life and presents a potential for serious risk to the health, safety, or welfare of a subject;
(iii) Is for a use of substantial importance in diagnosing, curing, mitigating, or treating disease, or otherwise preventing impairment of human health and presents a potential for serious risk to the health, safety, or welfare of a subject; or
(iv) Otherwise presents a potential for serious risk to the health, safety, or welfare of a subject.
Definition of "Implant." The term "implant" is defined at 21 C.F.R. § 812.3(d) as "a device that is placed into a surgically or naturally formed cavity of the human body if it is intended to remain there for a period of 30 days or more." This definition is significant for the present analysis because it establishes a durational threshold that directly affects the classification of the Lumina C14 sensor.
The Lumina C14 sensor is subcutaneously inserted, but it is designed for a 14-day (336-hour) wear duration, which is well below the 30-day threshold specified in the regulatory definition of "implant." Moreover, the C14 sensor is not placed into a surgically formed cavity; rather, it is inserted into the subcutaneous tissue of the abdomen or upper arm using a minimally invasive insertion device. Accordingly, the C14 sensor does not constitute an "implant" within the meaning of § 812.3(d), and the first prong of the SR definition — devices intended as implants — is not triggered.
Notwithstanding this conclusion, other aspects of the SR definition warrant analysis. The Lumina CGM System is a diagnostic device of "substantial importance in diagnosing" disease under § 812.3(m)(iii), as CGM devices play an increasingly central role in the management of diabetes mellitus. Additionally, the C14 sensor introduces energy into the subject through the application of a low-level electrical current to its working electrode for electrochemical glucose measurement and through BLE 5.2 radio frequency transmission. While the energy levels involved are low and are not expected to present a meaningful risk to subjects, these features must be considered in the overall SR/NSR analysis.
The SR/NSR determination is initially made by the sponsor in consultation with its regulatory and legal advisors, and the determination is then presented to the reviewing IRB for concurrence. The IRB has the authority and the obligation to independently evaluate the sponsor's risk assessment, the investigational plan, the informed consent documents, and the device description, and to make its own determination as to whether the proposed study involves a significant risk device. If the IRB concurs with the sponsor's NSR determination, the abbreviated IDE requirements apply and the study may proceed without an FDA IDE application.
However, it is important to note that FDA retains the authority to review and disagree with an NSR determination at any time. If FDA determines that a study classified as NSR by the sponsor and the IRB in fact involves a significant risk device, FDA may require the sponsor to submit a full IDE application before the study may continue.
D. Role of the IRB in NSR Determinations
Under 21 C.F.R. § 812.2(b), the reviewing IRB plays a critical gatekeeping role in the oversight of NSR device studies. Because NSR studies do not require FDA IDE application approval, the IRB serves as the primary regulatory body responsible for ensuring that the study is appropriately classified and that adequate safeguards are in place to protect study subjects.
For the LUMINA-US study, Clearwater Institutional Review Board LLC (IRB Registration No. IRB-2019-04821) will serve as the reviewing IRB for all six clinical sites. As part of its review and approval of the study, Clearwater IRB will be required to evaluate the following:
• Solstice's risk assessment and NSR determination, including the rationale for concluding that the Lumina CGM System does not present a significant risk to study subjects;
• The investigational plan (Protocol SBD-LUM-CL-001), including the study design, primary and secondary endpoints, inclusion and exclusion criteria, study procedures, and data analysis plan;
• The informed consent documents, which must comply with the requirements of 21 C.F.R. Part 50 and must adequately describe the risks, benefits, and alternatives associated with participation in the study;
• The device description, including the technical specifications of the C14 sensor and R7 reader/transmitter, the mechanism of action, the anticipated risks, and the applicable biocompatibility and safety data; and
• Any additional information relevant to the IRB's determination that the study may proceed as an NSR investigation.
If Clearwater IRB concurs that the LUMINA-US study is an NSR study, the abbreviated IDE requirements under § 812.2(b) will apply, and the study may proceed without submission of an IDE application to FDA. If, however, the IRB determines that the study involves a significant risk device, or if FDA subsequently disagrees with the NSR determination, a full IDE application will be required before the study may continue.
FDA has published guidance documents addressing the roles and responsibilities of IRBs in making SR/NSR determinations, including the Information Sheet Guidance document titled "Significant Risk and Nonsignificant Risk Medical Device Studies" (updated January 2006), which provides a framework for IRBs to use in evaluating proposed device studies. This guidance document identifies several categories of devices and studies that are generally considered to be NSR, and the principles articulated in the guidance support the conclusion that CGM accuracy studies with appropriate safeguards — including confirmatory reference measurements and restrictions on the use of investigational device data for treatment decisions — are appropriately classified as NSR.
IV. Application to the LUMINA-US Study
A. Analysis of 21 C.F.R. § 812.2(c)(3) Diagnostic Device Exemption
The threshold question is whether the LUMINA-US study qualifies for the diagnostic device exemption under 21 C.F.R. § 812.2(c)(3), which would exempt the study from the full scope of IDE requirements, including both the full IDE requirements applicable to SR studies and the abbreviated IDE requirements applicable to NSR studies.
The Lumina CGM System is indisputably a diagnostic device: it is intended to continuously measure and report glucose levels in interstitial fluid for the purpose of diabetes management. It does not deliver a therapeutic intervention, administer a drug, or otherwise treat the patient's underlying condition. Its sole function is to generate diagnostic information — real-time glucose values, trend data, and predictive alerts — that can be used by patients and healthcare providers to inform diabetes management decisions. Accordingly, the Lumina CGM System falls within the general category of "diagnostic devices" contemplated by § 812.2(c)(3).
However, the specific conditions of the § 812.2(c)(3) exemption must be evaluated on a condition-by-condition basis to determine whether the exemption applies to the LUMINA-US study:
Condition 1: Compliance with 21 C.F.R. Part 809. Part 809 governs in vitro diagnostic products for human use. The Lumina CGM System is not an in vitro diagnostic product — it measures glucose concentrations in vivo by means of a subcutaneously inserted electrochemical sensor. Accordingly, Part 809 is not directly applicable to the Lumina CGM System, and this condition does not present a barrier to the exemption. However, the inapplicability of Part 809 also means that the Lumina CGM System does not neatly fit within the category of diagnostic devices for which § 812.2(c)(3) was primarily designed.
Condition 2: Noninvasive vs. Invasive. This condition requires that the testing be noninvasive, or, if invasive, that it not present a significant risk beyond the risks inherent in the diagnostic procedure. The Lumina C14 sensor is an invasive device: it is subcutaneously inserted through the skin into the interstitial tissue. The R7 reader/transmitter, by contrast, is noninvasive, as it is worn externally on the upper arm and does not penetrate the skin or enter the body. The invasive nature of the C14 sensor complicates the direct application of the § 812.2(c)(3) exemption, as the provision was principally designed to address noninvasive diagnostic testing or testing using specimens collected by standard procedures. While the risks associated with subcutaneous sensor insertion are generally mild-to-moderate (as discussed in detail in Section IV.B below), the invasive character of the C14 raises questions about whether the exemption was intended to cover this type of device.
Condition 3: No Invasive Sampling Procedure Presenting Significant Risk. The LUMINA-US study does involve an invasive component — the subcutaneous insertion of the C14 sensor — but this insertion is performed using a minimally invasive, spring-loaded applicator device and does not constitute a "sampling procedure" in the traditional sense. Rather, the sensor remains in place and continuously measures glucose in the interstitial fluid without extracting a sample. This condition is likely satisfied, though the characterization of sensor insertion as something other than an invasive "sampling procedure" involves a degree of interpretive judgment.
Condition 4: No Introduction of Energy into the Subject. This condition requires that the testing not, by design or intention, introduce energy into the subject. The Lumina C14 sensor applies a small electrical potential (approximately 0.5–0.7 volts) to its working electrode for the purpose of electrochemical glucose measurement. Additionally, the C14 sensor transmits data to the R7 reader via BLE 5.2 radio frequency transmission, which involves the emission of radio frequency energy. While the energy levels are extremely low and are well within established safety limits, the device does, as a matter of technical fact, introduce energy into the subject. This condition is not met for purposes of the § 812.2(c)(3) exemption.
Condition 5: No Use as Sole Diagnostic Procedure Without Confirmation. The LUMINA-US study protocol expressly requires that all investigational glucose readings from the Lumina CGM System be confirmed by reference blood glucose measurements obtained using a YSI 2300 STAT Plus glucose and lactate analyzer (or equivalent validated reference method) at defined intervals during the study. The investigational device is not being used as the sole diagnostic basis for clinical decision-making during the study, and subjects are instructed not to make insulin dosing or other therapeutic decisions based solely on Lumina readings during their participation. This condition is satisfied.
Conclusion on § 812.2(c)(3). The strict diagnostic device exemption under 21 C.F.R. § 812.2(c)(3) may not fully apply to the LUMINA-US study. While several of the exemption's conditions are met, the Lumina C14 sensor is an invasive device that introduces energy into the subject, which likely takes the study outside the scope of the § 812.2(c)(3) exemption. The safer and more defensible analytical path is to evaluate the study under the NSR abbreviated IDE framework established by 21 C.F.R. § 812.2(b), which is addressed in the following section.
B. Analysis Under the NSR abbreviated IDE Framework
Having determined that the § 812.2(c)(3) diagnostic device exemption may not fully apply, we turn to the question of whether the LUMINA-US study qualifies as a non-significant risk device study under the abbreviated IDE framework of 21 C.F.R. § 812.2(b). This analysis requires an assessment of each factor set forth in the SR device definition at 21 C.F.R. § 812.3(m).
Factor (i): Implant. As discussed in Section III.C above, the Lumina C14 sensor is not an "implant" within the meaning of 21 C.F.R. § 812.3(d). The sensor is subcutaneously inserted but is designed for a 14-day (336-hour) wear duration, which is well below the 30-day threshold that defines an "implant" under the regulation. Furthermore, the C14 sensor is not placed into a surgically formed cavity; it is inserted into the subcutaneous tissue of the abdomen or the posterior aspect of the upper arm using a minimally invasive spring-loaded insertion device, which does not involve a surgical procedure or the creation of a body cavity. The insertion procedure is analogous to the insertion of a hypodermic needle and is performed by the study subject or a trained clinical site staff member without the need for anesthesia, incision, or surgical instrumentation.
Because the Lumina C14 sensor does not meet the regulatory definition of an "implant," this factor does not support classification of the LUMINA-US study as a significant risk study.
Factor (ii): Life-Supporting or Life-Sustaining. The Lumina CGM System is not intended as a life-supporting or life-sustaining device. While continuous glucose monitoring plays an important role in diabetes management and can contribute to improved glycemic control, the Lumina CGM System does not directly sustain a physiological function or replace a vital organ function. It monitors glucose levels and provides alerts, but it is not a substitute for blood glucose meters for therapeutic decisions, and it does not deliver insulin or any other therapeutic agent. The intended use statement in the LUMINA-US protocol specifically provides that the investigational device "is not intended to replace blood glucose monitoring for therapeutic decision-making" and that subjects must continue to use their existing blood glucose monitoring methods for all treatment decisions during the study period.
This factor does not support classification of the LUMINA-US study as a significant risk study.
Factor (iii): Substantial Importance in Diagnosing or Treating Disease. This factor requires consideration of whether the investigational device is of "substantial importance in diagnosing, curing, mitigating, or treating disease, or otherwise preventing impairment of human health." CGM devices are, as a general matter, of substantial importance in the management of diabetes mellitus, a chronic disease affecting approximately 37 million Americans. Continuous glucose monitoring has become a cornerstone of modern diabetes care, and the data generated by CGM systems inform critical therapeutic decisions, including insulin dosing, dietary adjustments, and exercise planning.
However, the relevance of this factor must be assessed in the context of the specific clinical study design, not merely in the abstract. FDA has historically treated CGM clinical accuracy studies as NSR when the study design incorporates appropriate safeguards to ensure that the investigational device is not relied upon for treatment decisions during the study. The LUMINA-US study protocol includes the following safeguards:
• All investigational glucose readings are confirmed by reference blood glucose measurements obtained using a YSI 2300 STAT Plus glucose and lactate analyzer (or equivalent validated reference method) at defined intervals;
• Subjects are specifically instructed in the informed consent document and in the study procedures that they may not make insulin dosing or other therapeutic decisions based solely on Lumina CGM System readings during the study period;
• The study protocol requires subjects to continue using their existing blood glucose monitoring methods (e.g., fingerstick blood glucose meters) for all treatment decisions during the study period; and
• The investigational device is labeled with the statement "CAUTION — Investigational Device. Limited by Federal (or United States) law to investigational use," and additional cautionary labeling states that the device "should not be used for making treatment decisions."
These safeguards are consistent with the approach taken in prior CGM accuracy studies that have been accepted by FDA as NSR studies. While this factor is relevant to the overall risk assessment, the mitigating effect of the study design safeguards is substantial, and this factor, on balance, does not compel an SR classification.
Factor (iv): Potential for Serious Risk. The final SR factor is a catch-all provision requiring assessment of whether the investigational device "otherwise presents a potential for serious risk to the health, safety, or welfare of a subject." This requires a comprehensive evaluation of the risks associated with use of the Lumina CGM System in the LUMINA-US study.
The principal risks associated with the Lumina C14 sensor include:
• Sensor insertion site infection: As with any device that penetrates the skin, there is a risk of localized infection at the sensor insertion site. This risk is mitigated by the use of aseptic technique during insertion, the limited 14-day wear duration, and the provision of instructions to subjects regarding proper site care and monitoring for signs of infection.
• Local skin irritation and allergic contact dermatitis: The sensor adhesive and the materials of the sensor housing may cause localized skin irritation or allergic reactions in some subjects. This risk is generally mild and self-limiting.
• Minor bleeding at the insertion site: Subcutaneous insertion of the sensor may cause minor bleeding or bruising at the insertion site, which is typically self-resolving.
• Allergic reaction to sensor materials: The PtIr-4G electrode coating is a novel material that has not been used in the predicate devices. While platinum-iridium alloys have a long history of biocompatible use in medical devices, the specific PtIr-4G formulation is proprietary to Solstice and has not been independently evaluated in the context of a U.S. clinical study. Biocompatibility testing is currently underway at Whitmore Laboratories Inc. to characterize the biological response to this material.
• Sensor fracture or breakage: There is a theoretical risk that the sensor filament could fracture during insertion or removal, though the C14 sensor has been designed with breakage-resistant construction and this event has not been observed in EU commercial experience to date.
Critically, the risk profile of the Lumina C14 sensor is well-characterized based on the EU commercial experience accumulated since the product's launch in September 2024. The System was CE-marked under the EU MDR following a comprehensive conformity assessment by Meridian Conformity Assessment GmbH (Notified Body 0483), and post-market surveillance data collected since the September 2024 commercial launch have not identified any serious device-related adverse events attributable to the Lumina CGM System. This post-market surveillance data, while generated outside the United States, provides valuable real-world evidence supporting the characterization of the device's risks as mild-to-moderate.
Based on the foregoing analysis, the risks associated with the Lumina C14 sensor in the context of the LUMINA-US study are generally mild-to-moderate, well-characterized, and consistent with the risks accepted by FDA and reviewing IRBs for prior NSR CGM studies. This factor does not support an SR classification.
Overall NSR Conclusion. Considering all four factors of the SR definition at 21 C.F.R. § 812.3(m), we conclude that the LUMINA-US study presents a non-significant risk profile. The Lumina C14 sensor is not an "implant" under the regulatory definition; the Lumina CGM System is not life-supporting or life-sustaining; the study protocol incorporates robust safeguards to ensure that the investigational device is not relied upon for treatment decisions; and the risks associated with subcutaneous sensor insertion are mild-to-moderate and well-characterized based on EU commercial experience. The LUMINA-US study may therefore proceed as an NSR study under the abbreviated IDE requirements of 21 C.F.R. § 812.2(b), subject to IRB concurrence and the recommended Pre-Sub confirmation discussed in Section VI.
C. Comparison to Prior FDA Determinations for Similar CGM Studies
The conclusion that the LUMINA-US study qualifies as an NSR study is strongly supported by the precedent established through prior FDA interactions with sponsors of similar CGM clinical studies.
NovaSense GlucoTrack NX-500 (510(k) No. K211034, cleared June 18, 2022). The NovaSense GlucoTrack NX-500 is one of the two identified predicate devices for Solstice's planned 510(k) submission. The NX-500 is a subcutaneous CGM system with a 10-day sensor wear duration. The clinical studies supporting the NX-500's 510(k) clearance were conducted under the NSR abbreviated IDE framework with IRB oversight; a full IDE application was not submitted to FDA for those studies. The successful clearance of the NX-500 based on clinical data generated in NSR studies confirms that FDA has accepted the NSR framework as appropriate for subcutaneous CGM accuracy studies.
NovaSense GlucoTrack NX-700 (510(k) No. K230489, cleared March 7, 2024). The NovaSense GlucoTrack NX-700 is the secondary predicate device for Solstice's planned 510(k) submission. The NX-700 is a subcutaneous CGM system with a 14-day sensor wear duration — directly analogous to the Lumina C14. The clinical studies supporting the NX-700's 510(k) clearance were likewise conducted under the NSR abbreviated IDE framework with IRB oversight. This precedent is particularly significant because the NX-700's 14-day wear duration matches the Lumina C14's wear duration exactly, demonstrating that a 14-day subcutaneous CGM sensor study has been accepted by FDA as NSR.
FDA Guidance Documents. Several FDA guidance documents provide additional support for treating CGM sensor accuracy studies as NSR investigations:
• "Integrated Continuous Glucose Monitoring Systems" (September 2023): This guidance document, which addresses the performance and labeling requirements for iCGM systems, discusses the clinical study expectations for CGM systems seeking iCGM classification. While the guidance does not directly address IDE requirements, the clinical performance testing described in the guidance is consistent with the NSR study framework, and the guidance does not suggest that a full IDE application is expected for CGM accuracy studies.
• "Factors to Consider When Making Benefit-Risk Determinations in Medical Device Premarket Approval and De Novo Classifications": This guidance provides a framework for evaluating the benefits and risks of medical devices, including diagnostic devices. The benefit-risk framework articulated in this guidance supports the conclusion that the risks associated with subcutaneous CGM sensor use are outweighed by the benefits of the diagnostic information generated, and that the residual risks are not of sufficient severity to warrant an SR classification.
• FDA Information Sheet Guidance for IRBs: "Significant Risk and Nonsignificant Risk Medical Device Studies": This guidance provides the framework used by IRBs in evaluating proposed device studies and making SR/NSR determinations. The guidance identifies several categories of devices that are generally considered to present significant risk (e.g., devices intended as implants with wear durations of 30 days or more, devices used to support or sustain life) and several categories that are generally considered to present nonsignificant risk. CGM accuracy studies with appropriate safeguards — including confirmatory reference measurements and restrictions on the use of investigational device readings for treatment decisions — are generally identified as NSR under the principles set forth in this guidance.
Taken together, these precedents and guidance documents provide substantial support for the position that the LUMINA-US study qualifies as a non-significant risk study and may proceed under the abbreviated IDE framework of 21 C.F.R. § 812.2(b).
D. Remaining Considerations and Risk Factors
While the overall weight of the analysis supports an NSR classification for the LUMINA-US study, several factors warrant disclosure and continued monitoring, as they could affect FDA's assessment of the study's risk profile:
14-Day Wear Duration. The Lumina C14 sensor's 14-day wear duration is at the higher end of currently cleared subcutaneous CGM sensors in the U.S. market. While this duration matches the NovaSense NX-700 (14 days) and is well below the 30-day threshold that defines an "implant" under § 812.3(d), it is longer than many other commercially available CGM sensors (which typically range from 7 to 10 days). The longer wear duration could theoretically increase the risk of sensor insertion site infection or skin irritation, though these risks remain mild-to-moderate and are adequately addressed by the study protocol's monitoring procedures. This factor should not independently trigger an SR classification, but it may attract additional scrutiny from the reviewing IRB and from FDA at the Pre-Sub meeting.
Novel PtIr-4G Electrode Coating. The Lumina C14 sensor incorporates a proprietary platinum-iridium electrode coating designated as PtIr-4G technology, which is not present in the predicate devices (the NovaSense NX-500 and NX-700 utilize conventional platinum electrode coatings). The novelty of this material introduces an element of uncertainty regarding the biocompatibility profile of the C14 sensor, notwithstanding the generally favorable biocompatibility characteristics of platinum-iridium alloys and the absence of serious adverse events in EU post-market surveillance data.
To address this concern, Solstice has engaged Whitmore Laboratories Inc. (A2LA Certificate No. 3847.01, accredited under ISO/IEC 17025) to conduct a comprehensive biocompatibility testing program for the C14 sensor and its PtIr-4G electrode coating. The biocompatibility testing scope encompasses the full ISO 10993 battery applicable to devices with subcutaneous contact of limited duration (≤ 30 days), including:
• Cytotoxicity (ISO 10993-5)
• Sensitization (ISO 10993-10)
• Irritation (ISO 10993-10)
• Acute systemic toxicity (ISO 10993-11)
• Subchronic systemic toxicity (ISO 10993-11)
• Implantation (ISO 10993-6)
• Hemocompatibility (ISO 10993-4)
• Genotoxicity (ISO 10993-3)
The target completion date for the biocompatibility testing program is August 31, 2025, and the testing budget is $485,000. The results of this testing will be critical not only for the 510(k) submission but also for supporting the NSR risk characterization in the IRB submission to Clearwater IRB and in the Pre-Sub meeting package to FDA. If the biocompatibility testing reveals any unexpected findings regarding the PtIr-4G material, the NSR determination may need to be reassessed.
The novelty of the PtIr-4G electrode coating could prompt FDA to scrutinize the NSR determination more closely at the Pre-Sub meeting, and this reinforces our recommendation to seek explicit FDA confirmation of the study's NSR classification.
LuminaPredict Algorithm v2.1. The proprietary LuminaPredict Algorithm v2.1 differs from the algorithms used in the predicate devices, and its software level of concern has been classified as Major under FDA's guidance on premarket submissions for software-containing devices. However, this classification pertains to the premarket submission requirements for the 510(k) review and does not directly bear on the SR/NSR determination for the clinical study. The algorithm's performance will be evaluated as part of the LUMINA-US study (sensor accuracy is a function of both the hardware and the algorithmic processing of raw sensor signals), but the algorithm itself does not introduce a risk to study subjects that would elevate the study to SR status. We note this factor for completeness but do not consider it material to the NSR determination.
BLE 5.2 Wireless Transmission and Cybersecurity. The Lumina C14 sensor's use of BLE 5.2 wireless transmission introduces cybersecurity considerations, including the theoretical risk of unauthorized access to or manipulation of transmitted glucose data. While cybersecurity is an important regulatory consideration — and one that FDA has increasingly emphasized in recent guidance documents — it does not directly affect the SR/NSR determination for the clinical study. Cybersecurity will be addressed in the 510(k) submission, and the LUMINA-US study protocol includes provisions for data integrity monitoring.
Risk of FDA Disagreement. If FDA were to disagree with the NSR determination — whether at the Pre-Sub meeting, during the 510(k) review, or at any other point — a full IDE application would be required before the LUMINA-US study could proceed (or continue). This would require submission of FDA Form 3640, a complete investigational plan, manufacturing and quality control documentation, and a comprehensive risk analysis. FDA's review period for an IDE application is approximately 30 days from receipt, though this timeline may be extended if FDA requests additional information or if deficiencies are identified in the application. In practical terms, the preparation, submission, and review of a full IDE application would likely delay the study start target of September 15, 2025 by approximately three to four months.
The potential consequences of such a delay underscore the importance of confirming the NSR determination with FDA through the Pre-Sub meeting process, as discussed in Section VI.B below.
V. Obligations Under the NSR abbreviated IDE
Even though the LUMINA-US study is expected to qualify as an NSR study and the § 812.2(c)(3) diagnostic device exemption does not strictly apply, the abbreviated IDE requirements under 21 C.F.R. § 812.2(b) impose substantive compliance obligations that Solstice must satisfy throughout the duration of the study. Failure to comply with these requirements could result in FDA enforcement action, IRB suspension of the study, or compromised data integrity that could jeopardize the 510(k) submission. The following obligations apply:
Informed Consent (21 C.F.R. Part 50). Solstice must ensure that all study subjects provide legally effective informed consent prior to enrollment in the LUMINA-US study. The informed consent form must comply with the requirements of 21 C.F.R. Part 50, Subpart B, including adequate disclosure of the purpose of the study, the procedures to be performed, the reasonably foreseeable risks and discomforts, the expected benefits, the available alternatives, the confidentiality protections, and the subject's right to withdraw at any time. The informed consent form must be reviewed and approved by Clearwater IRB as part of the IRB's initial review of the study. Calderwood & Harkness has prepared a comprehensive review and markup of the draft informed consent form for the LUMINA-US study, which has been provided to Dr. Tierney under separate cover.
IRB Review and Approval (21 C.F.R. Part 56). The LUMINA-US study must be approved by an IRB that meets the requirements of 21 C.F.R. Part 56 before the study may commence at any clinical site. Clearwater Institutional Review Board LLC (IRB Registration No. IRB-2019-04821) will serve as the reviewing IRB for all six clinical sites, providing centralized IRB oversight. The IRB must conduct both initial review and approval of the study and continuing review at intervals appropriate to the degree of risk, but not less than once per year. The IRB submission package must include the study protocol, the informed consent form, the investigator's brochure, the device description and risk assessment, and the sponsor's NSR determination with supporting rationale.
Labeling (21 C.F.R. § 812.5). All investigational devices used in the LUMINA-US study must be labeled in accordance with 21 C.F.R. § 812.5. This includes, at a minimum, the following labeling elements: the name and place of business of the manufacturer; the quantity of contents; all relevant contraindications, hazards, adverse effects, interfering substances, warnings, and precautions; and the statement "CAUTION — Investigational Device. Limited by Federal (or United States) law to investigational use." The labeling must not bear any false or misleading statements and must not represent the device as safe or effective for the purposes for which it is being investigated.
Monitoring (21 C.F.R. § 812.46). Solstice, as the sponsor of the LUMINA-US study, is required to monitor the investigation to ensure that the study is conducted in accordance with the investigational plan, applicable regulatory requirements, and the conditions of IRB approval. Under the anticipated master services agreement, Veltrano CRO (Dr. Lisa Fontaine, VP of Clinical Operations) will perform monitoring activities on Solstice's behalf, including site initiation visits, periodic monitoring visits, and close-out visits. The monitoring plan must be documented and must address, at a minimum, verification of informed consent processes, protocol compliance, adverse event reporting, data integrity, and investigational device accountability.
Records and Reports (21 C.F.R. §§ 812.140, 812.150). Solstice must maintain complete and accurate records of the investigation in accordance with 21 C.F.R. § 812.140, including records of the receipt, use, and disposition of all investigational devices; records of each subject's case history and exposure to the investigational device; and records of the signed informed consent forms. Additionally, Solstice must comply with the reporting requirements of 21 C.F.R. § 812.150, including the reporting of unanticipated adverse device effects ("UADEs") to the reviewing IRB, all participating investigators, and FDA within specified timeframes. Specifically, UADEs must be reported to the IRB and all investigators within 10 working days after the sponsor first receives notice of the effect, and a report must also be submitted to FDA.
Device Disposition (21 C.F.R. § 812.140(a)). Solstice must maintain accountability for all investigational devices shipped to clinical sites, including records of the number of devices shipped, the number used, the number returned, and the disposition of all unused devices. Investigational devices that are not used in the study must be returned to the sponsor or otherwise disposed of in accordance with applicable regulatory requirements.
These obligations must be incorporated into the Veltrano CRO master services agreement, which is currently under negotiation. Calderwood & Harkness will review the master services agreement to ensure that the abbreviated IDE compliance obligations are appropriately allocated and documented. Additionally, these obligations must be reflected in the Clearwater IRB submission package, and Solstice's internal standard operating procedures for clinical study management should be updated as necessary to address the abbreviated IDE requirements.
VI. Recommendation
A. Primary Recommendation
Based on the analysis set forth in this memorandum, Calderwood & Harkness concludes that the LUMINA-US clinical study (Protocol SBD-LUM-CL-001) likely qualifies as a non-significant risk (NSR) diagnostic device study under the abbreviated IDE framework of 21 C.F.R. § 812.2(b).
The strict diagnostic device exemption under 21 C.F.R. § 812.2(c)(3) may not fully apply to the LUMINA-US study due to the invasive nature of the Lumina C14 sensor and its introduction of energy into the subject, as discussed in Section IV.A above. However, the study qualifies under the broader NSR abbreviated IDE pathway established by 21 C.F.R. § 812.2(b). Under this pathway, the study may proceed upon IRB approval without the need for submission of an IDE application to FDA, provided that Solstice complies with the abbreviated IDE requirements detailed in Section V above.
The NSR determination is supported by the following key findings:
• The Lumina C14 sensor is not an "implant" within the meaning of 21 C.F.R. § 812.3(d), as its 14-day wear duration is well below the 30-day threshold;
• The Lumina CGM System is not a life-supporting or life-sustaining device;
• The LUMINA-US study protocol incorporates robust safeguards, including confirmatory reference measurements and restrictions on the use of investigational device data for treatment decisions, that mitigate the risks associated with the device's diagnostic importance;
• The risks associated with subcutaneous sensor insertion are mild-to-moderate and well-characterized based on EU post-market surveillance data; and
• FDA has consistently accepted NSR determinations for clinical studies of analogous subcutaneous CGM systems, including the NovaSense GlucoTrack NX-700, which has an identical 14-day sensor wear duration.
The reviewing IRB — Clearwater Institutional Review Board LLC (IRB Registration No. IRB-2019-04821) — must concur with the NSR determination as part of its review and approval of the LUMINA-US study. Solstice should provide Clearwater IRB with a comprehensive risk assessment and NSR determination rationale, including the analysis set forth in this memorandum (subject to appropriate privilege considerations) and any supporting documentation, including EU post-market surveillance data and available biocompatibility testing results.
B. Confirmation via Pre-Sub Meeting
We strongly recommend that Solstice include a specific question regarding IDE exemption applicability in the Pre-Submission ("Pre-Sub") meeting package to be submitted to FDA CDRH, Office of Health Technology 2, Division of Chemistry and Toxicology Devices ("OHT2-DCT"), on June 16, 2025, in advance of the Pre-Sub meeting scheduled for August 14, 2025.
The Pre-Sub question should concisely describe the LUMINA-US study design — including the device description, the study population, the primary and secondary endpoints, the study safeguards (confirmatory reference measurements, restrictions on treatment decision-making based on investigational device data), and the NSR risk assessment — and should ask FDA to confirm that the LUMINA-US study may proceed as a non-significant risk study under IRB oversight without a separate IDE application.
Obtaining FDA's explicit agreement with the NSR determination at the Pre-Sub meeting will provide Solstice with critical regulatory certainty before the planned study commencement date of September 15, 2025. It will also substantially mitigate the risk of FDA subsequently disagreeing with the NSR determination during the 510(k) review or at any other point during the study, which could require submission of a full IDE application, interruption of the study, and significant delays to the downstream regulatory timeline.
Calderwood & Harkness will draft the relevant Pre-Sub question in coordination with Pinnacle Regulatory Consulting Group LLC (Dr. Sandra Ellison, Regulatory Strategy Lead, and Thomas Greenbaum, Regulatory Affairs Specialist) as part of the broader Pre-Sub meeting package preparation. Our target is to complete the draft Pre-Sub question by June 10, 2025, to allow adequate time for internal review and finalization before the June 16, 2025 package submission deadline.
C. Contingency Planning
While we believe the NSR determination is well-supported by the regulatory framework, precedent, and the specific facts of the LUMINA-US study, prudent regulatory planning requires that Solstice be prepared for the possibility that FDA may indicate — at the Pre-Sub meeting or otherwise — that the LUMINA-US study should be classified as a significant risk study.
In the event of an SR classification, Solstice would be required to submit a full IDE application to FDA before the LUMINA-US study could proceed. A full IDE application would require the preparation and submission of the following materials:
• FDA Form 3640 (Application for an Investigational Device Exemption);
• A complete investigational plan, including the study protocol, statistical analysis plan, case report forms, and informed consent documents;
• A detailed description of the investigational device, including spec