MEMORANDUM
PRIVILEGED AND CONFIDENTIAL — ATTORNEY-CLIENT COMMUNICATION ATTORNEY WORK PRODUCT
From: Miriam Calloway, Partner, and Amy Whitfield, Associate Calderwood & Harkness LLP 1401 K Street NW, Suite 900 Washington, D.C. 20005
To: Dr. Niamh Tierney, VP of Regulatory Affairs, Solstice Biomedical Devices Ltd. Marcus Hale, VP of U.S. Operations, Solstice Biomedical Inc.
CC: Joel Strauss, Partner, Calderwood & Harkness LLP Fiona Drennan, Quality Assurance Director, Solstice Biomedical Devices Ltd. Dr. Sandra Ellison, Managing Director, Pinnacle Regulatory Consulting Group LLC Thomas Greenbaum, Senior Regulatory Specialist, Pinnacle Regulatory Consulting Group LLC
Date: May 12, 2025
Re: Labeling Review — Solstice Lumina™ CGM System (Lumina C14 Sensor and Lumina R7 Reader/Transmitter) — Review of Draft Device Labeling for Compliance with 21 C.F.R. Part 801 and Applicable FDA Guidance
Engagement Reference No.: 1037-00002
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I. Purpose and Scope
Calderwood & Harkness LLP ("C&H") has been engaged by Solstice Biomedical Devices Ltd. ("SBD") and its U.S. subsidiary, Solstice Biomedical Inc. ("SBI"), to conduct a comprehensive review of the draft labeling package for the Solstice Lumina™ Continuous Glucose Monitoring System (the "Lumina CGM System" or "Lumina System"). The Lumina CGM System comprises two primary components: the Lumina C14 implantable sensor (the "C14 Sensor") and the Lumina R7 wearable reader/transmitter (the "R7 Reader"). This memorandum sets forth the findings and recommendations resulting from our review, undertaken in preparation for inclusion of the labeling package in the planned premarket notification submission under Section 510(k) of the Federal Food, Drug, and Cosmetic Act ("FD&C Act"), 21 U.S.C. § 360(k). The target submission date for the 510(k) is April 30, 2026.
The scope of our review encompasses the three principal components of the draft labeling package delivered to C&H on March 28, 2025, via secure file transfer:
1. Instructions for Use (IFU): The multi-page patient-facing booklet providing comprehensive setup, operation, troubleshooting, and safety information for the Lumina CGM System (Draft Revision 04, dated March 15, 2025).
2. Package Labeling: Both the outer carton labeling for the C14 Sensor and R7 Reader, respectively, and the inner carton labeling for individual sensor pouches (Draft Revision 03, dated March 10, 2025).
3. Physician Labeling (Healthcare Professional Guide): The summary guide intended for prescribing healthcare professionals, covering clinical indications, contraindications, warnings, precautions, device specifications, and clinical study data summaries (Draft Revision 02, dated March 12, 2025).
Our review has been conducted against the requirements of 21 C.F.R. Part 801 (Labeling), 21 C.F.R. § 809.10 (labeling for in vitro diagnostic products, to the extent applicable to the Lumina CGM System's glucose measurement function), and relevant FDA guidance documents pertaining to continuous glucose monitoring devices. In particular, we have evaluated the draft labeling against the FDA's guidance document titled "Integrated Continuous Glucose Monitoring Systems" (September 2023), which establishes specific labeling recommendations for devices seeking classification as integrated continuous glucose monitoring systems ("iCGM"). We have also considered the cybersecurity labeling requirements set forth in the FDA's September 2023 guidance, "Cybersecurity in Medical Devices: Quality System Considerations and Content of Premarket Submissions."
We note that Solstice provided the draft labeling adapted from its existing European Union Medical Device Regulation ("EU MDR") labeling, which was approved under CE certificate MCA-2024-07319, issued on September 12, 2024, by Meridian Conformity Assessment GmbH (Notified Body 0483). While the EU MDR labeling provides a useful foundation, our review has identified numerous areas where U.S.-specific modifications are required to achieve compliance with FDA's distinct regulatory framework. This memorandum identifies those modifications and provides prioritized recommendations for remediation.
The draft labeling was prepared with substantive input from Pinnacle Regulatory Consulting Group LLC ("Pinnacle"), and we have coordinated with Dr. Sandra Ellison and Thomas Greenbaum of Pinnacle in the course of this review to ensure alignment between our legal and regulatory compliance assessment and Pinnacle's technical regulatory work on the broader 510(k) submission package.
This memorandum is intended to serve as a working document for the Solstice regulatory affairs, quality assurance, and engineering teams, as well as for Pinnacle, to guide the labeling revision process over the coming months. We expect that certain issues identified herein—particularly those relating to the device's classification as an iCGM, the acceptability of specific insertion sites, and the adjunctive versus non-adjunctive use determination—will be informed by FDA feedback at the planned Pre-Submission ("Pre-Sub") meeting, which is targeted for August 14, 2025.
II. Regulatory Framework for Device Labeling
A. Statutory and Regulatory Requirements
The labeling of medical devices in the United States is governed by a comprehensive statutory and regulatory framework rooted in the FD&C Act and its implementing regulations. The following provisions are of principal relevance to the Lumina CGM System labeling review.
Sections 501 and 502 of the FD&C Act. Section 501 (21 U.S.C. § 351) establishes the adulteration provisions, which include requirements relating to the conformity of a device with its labeling. Section 502 (21 U.S.C. § 352) sets forth the misbranding provisions, which deem a device misbranded if, among other things, its labeling is false or misleading in any particular, if its labeling does not bear adequate directions for use, or if its labeling fails to bear required warnings and precautions. A device whose labeling does not conform to the requirements of Section 502 is subject to enforcement action, including seizure, injunction, and civil monetary penalties. Compliance with the labeling requirements discussed in this memorandum is therefore essential not only for the success of the 510(k) submission but also for the ongoing lawful marketing of the Lumina CGM System in the United States.
21 C.F.R. Part 801 — General Device Labeling. Part 801 of Title 21 of the Code of Federal Regulations implements the statutory labeling requirements for medical devices. The following specific sections are relevant to the Lumina CGM System:
21 C.F.R. § 801.1 — Medical devices; name and place of business of manufacturer, packer, or distributor. This section requires that the label of a device bear the name and place of business of the manufacturer, packer, or distributor. The name must be the actual corporate name, and the place of business must include the street address, city, state, and zip code. If the device is not manufactured by the person whose name appears on the label, the label must qualify the name with a phrase such as "Manufactured for," "Distributed by," or "Manufactured by [name], Distributed by [name]."
21 C.F.R. § 801.5 — Medical devices; adequate directions for use. This section requires that labeling bear adequate directions for use, defined as directions under which the layperson can use the device safely and for the purposes for which it is intended. For prescription devices, this requirement is subject to the exemption in § 801.109.
21 C.F.R. § 801.6 — Medical devices; misleading statements. Among other provisions, this section provides that labeling is misleading if it contains any representation or suggestion that the device is safe or effective for a use for which it is not intended.
21 C.F.R. § 801.15 — Medical devices; prominence of required label statements. All required label statements must appear prominently, conspicuously, and in terms that are likely to be read and understood by the ordinary individual under customary conditions of purchase and use. Required label statements must appear on the principal display panel or, if permitted, on the information panel.
21 C.F.R. § 801.63 — Medical devices; date of manufacture. (Note: This section addresses name and place of business of manufacturer, packer, or distributor on the label.) The device label must include the name and place of business information sufficient to allow the FDA and consumers to contact the responsible entity.
21 C.F.R. § 801.109 — Exemptions for devices for use by or on the order of a physician. This section exempts prescription devices from the requirement to bear adequate directions for lay use, provided that certain conditions are met. Specifically, the device must bear the statement "Caution: Federal law restricts this device to sale by or on the order of a _" (with the blank filled in with the appropriate licensed practitioner designation), or alternatively, the symbol "Rx only." Additionally, the device must bear labeling that provides adequate information for the prescribing practitioner to use the device safely and for its intended purpose. This is the operative exemption for the Lumina CGM System, as it is a prescription device.
21 C.F.R. § 862.1355 — Glucose test system. The Lumina CGM System is expected to be classified under product code QKQ, which corresponds to the glucose test system classification at 21 C.F.R. § 862.1355. This classification carries specific labeling requirements associated with the special controls applicable to glucose test systems, including requirements for accuracy labeling, performance data, and use-condition limitations.
B. Applicable FDA Guidance Documents
In addition to the statutory and regulatory requirements, several FDA guidance documents bear directly on the Lumina CGM System's labeling. While FDA guidance documents are not binding and do not establish legally enforceable responsibilities, they represent the Agency's current thinking and are closely followed by review divisions in evaluating premarket submissions. Departures from guidance recommendations should be justified and may invite additional FDA scrutiny.
The following guidance documents are of particular relevance:
"Integrated Continuous Glucose Monitoring Systems" (September 2023). This is the single most important guidance document for the Lumina CGM System's labeling review. It provides specific recommendations for labeling of devices seeking iCGM classification, including: (i) accuracy performance labeling requirements (including MARD thresholds and consensus error grid reporting); (ii) alert and alarm labeling requirements, including default threshold specifications and configurable range disclosures; (iii) interoperability labeling, particularly for iCGM devices intended to communicate data to compatible automated insulin delivery (AID) systems and other diabetes management devices; and (iv) specific warning and precaution language regarding adjunctive versus non-adjunctive use determinations.
"Guidance for Industry and FDA Staff: Factors to Consider Regarding Benefit-Risk in Medical Device Product Availability, Compliance, and Enforcement Decisions." While primarily directed at FDA's own enforcement discretion, this guidance informs the benefit-risk framework within which labeling claims and warnings are evaluated.
"Guidance for the Content of Premarket Submissions for Software Contained in Medical Devices." This guidance is relevant to the Lumina CGM System's software components, including the LuminaPredict Algorithm (v2.1), the Lumina Firmware (v3.4.2), the Lumina Reader OS (v2.1.0), and the Lumina Mobile App (v1.0.3). Software-related labeling claims—including claims regarding algorithm performance, trend arrow generation, and predictive alert features—must be consistent with the software documentation provided in the 510(k) submission.
"Cybersecurity in Medical Devices: Quality System Considerations and Content of Premarket Submissions" (September 2023). This guidance establishes FDA's expectations for cybersecurity-related labeling, including instructions for software updates, security patch management, data encryption disclosures, and recommended user actions for maintaining device cybersecurity. The Lumina CGM System's wireless communication via BLE 5.2 and its mobile application connectivity make cybersecurity labeling a significant concern.
FDA Labeling Guidance for the Unique Device Identification (UDI) System under 21 C.F.R. Part 830. The UDI rule requires that device labels and packages bear a unique device identifier in both human-readable and machine-readable (AIDC) formats. The Lumina CGM System must comply with UDI requirements, including submission of device information to the Global Unique Device Identification Database (GUDID).
C. Special Controls for iCGM Classification
A threshold issue for the Lumina CGM System's labeling is whether the device will be classified as an integrated continuous glucose monitoring system (iCGM). The iCGM classification was established through De Novo classification (DEN170088) and carries specific special controls that directly impact labeling content. If the Lumina CGM System is classified as an iCGM—a determination to be confirmed through the Pre-Sub meeting with FDA's Center for Devices and Radiological Health (CDRH), Office of Health Technology 2 (OHT2), Division of Chemistry and Toxicology Devices, targeted for August 14, 2025—the following additional labeling requirements will apply:
(a) Interoperability labeling identifying the device as an iCGM and describing its ability to communicate glucose data to compatible devices, including AID systems and other diabetes management applications, through a standardized data interface.
(b) Accuracy performance labeling specifying that the device meets the iCGM special controls accuracy criteria, including a mean absolute relative difference (MARD) of ≤ 9.0% and consensus error grid results demonstrating ≥ 99% of readings falling within Zones A and B. These performance thresholds must be accurately reflected in the labeling based on clinical study data.
(c) Specific alert and alarm labeling meeting the iCGM special controls for timely notification of glucose excursions, including hypoglycemia and hyperglycemia alerts with specified latency requirements.
We note that the MARD target of ≤ 9.0% and the consensus error grid target of ≥ 99% Zones A+B represent the minimum performance thresholds for iCGM classification. The Lumina CGM System's actual performance, as measured in the LUMINA-US clinical study, must meet or exceed these thresholds, and the labeling must accurately report the study results. Any discrepancy between claimed and demonstrated performance would constitute misbranding and would likely result in an unsuccessful 510(k) submission.
III. Summary of Draft Labeling Components Reviewed
A. Instructions for Use (IFU)
The draft IFU is a multi-page booklet (currently approximately 68 pages, Draft Revision 04, dated March 15, 2025) that has been adapted from the EU MDR IFU approved in connection with CE certificate MCA-2024-07319. The IFU is organized into the following principal sections: system overview and component descriptions; initial setup and mobile application pairing (Lumina Mobile App v1.0.3); C14 sensor insertion procedure; R7 reader operation and configuration; glucose reading interpretation, including trend arrows and 8-hour trend graphs; configurable hypoglycemia and hyperglycemia alert settings; troubleshooting and error codes; device maintenance, cleaning, and storage; and sensor disposal procedures.
The IFU references the following software versions: Lumina Firmware v3.4.2 (embedded in the C14 Sensor); Lumina Reader OS v2.1.0 (operating system for the R7 Reader); LuminaPredict Algorithm v2.1 (the proprietary algorithm that processes raw sensor signals to generate glucose values and predictive trend data); and Lumina Mobile App v1.0.3 (the companion mobile application compatible with iOS 16.0+ and Android 13.0+ operating systems).
The IFU is generally comprehensive in its coverage of device operation and user-facing functionality. However, as detailed in Sections IV through X of this memorandum, there are numerous deficiencies that must be addressed before the IFU is suitable for inclusion in the U.S. 510(k) submission. These deficiencies range from critical issues—such as the mismatch between the EU-approved indication (adults and children aged 4 years and older) and the U.S. intended use (adults aged 18 years and older)—to medium-priority matters such as British English spelling conventions that should be Americanized.
B. Package Labeling (Outer and Inner Carton)
The draft package labeling encompasses the outer carton labeling for the C14 Sensor (sold in packs of 2 sensors per carton) and the R7 Reader, as well as the inner carton labeling for individual sensor pouches. The outer carton labeling currently includes product identification, lot number fields, expiration date fields, storage condition icons, and certain regulatory symbols. The inner carton labeling for the individual sensor pouches includes the device name, lot number, expiration date, sterilization method symbol, and single-use symbol.
As presently drafted, the package labeling reflects EU market requirements and includes the CE mark symbol (CE 0483), references to the EU MDR (Regulation (EU) 2017/745), and identification of Meridian Conformity Assessment GmbH as the notified body. These EU-specific elements must be either removed from or clearly segregated within the U.S. labeling. Additional U.S.-specific elements that are currently absent—including the Rx Only legend, UDI in human-readable and machine-readable formats, and U.S. establishment identification—must be incorporated as described in Section IV of this memorandum.
C. Physician Labeling (Healthcare Professional Guide)
The draft physician labeling is a summary guide intended for prescribing healthcare professionals. It covers clinical indications for use, contraindications, warnings, precautions, sensor technical specifications, and a clinical study data summary. The guide is approximately 24 pages in its current draft form (Draft Revision 02, dated March 12, 2025).
The clinical study data section of the physician labeling currently references data from the EU pivotal clinical study conducted in support of the CE marking application. This data will need to be updated with the results of the LUMINA-US study (Protocol SBD-LUM-CL-001, conducted under the oversight of Veltrano Clinical Research Organization Inc.) once those results become available, which is currently anticipated by March 15, 2026. The physician labeling also requires updating of the clinical indications section to match the U.S. Indications for Use Statement (FDA Form 3881) and the addition of several contraindications, warnings, and precautions that are standard for CGM device labeling in the U.S. market.
IV. General Labeling Deficiencies and Recommendations
This section addresses labeling deficiencies that are cross-cutting—i.e., they affect multiple or all components of the labeling package. Section-specific deficiencies are addressed in subsequent sections of this memorandum.
A. Establishment Identification (21 C.F.R. § 801.1 and § 801.63)
Deficiency: The draft labeling, across all three components (IFU, package labeling, and physician labeling), identifies only Solstice Biomedical Devices Ltd. as the device manufacturer, with the address listed as Unit 14, Liffey Innovation Park, Chapelizod, Dublin D20 FX72, Ireland. The U.S. labeling must also identify the U.S. establishment—Solstice Biomedical Inc. ("SBI"), located at 220 Westbrook Drive, Suite 400, Cambridge, MA 02142—as the entity responsible for distributing the device in the United States and as the 510(k) holder. The failure to include the U.S. establishment identification on the labeling creates a misbranding concern under 21 C.F.R. § 801.1 and could complicate FDA's ability to associate the device with the appropriate domestic establishment registration.
Recommendation: All labeling components should be revised to include the following dual identification:
"Manufactured by: Solstice Biomedical Devices Ltd., Unit 14, Liffey Innovation Park, Chapelizod, Dublin D20 FX72, Ireland"
"Distributed by: Solstice Biomedical Inc., 220 Westbrook Drive, Suite 400, Cambridge, MA 02142, USA"
The designation "Distributed by" is appropriate for SBI if SBI is not engaged in the manufacturing of the device. Alternatively, if SBI performs any manufacturing activities (including specification development, design control, or final release activities), the designation "Manufactured for" or a co-manufacturer designation may be more appropriate. C&H recommends confirming SBI's role with respect to manufacturing activities for purposes of label designation accuracy. In all cases, the establishment identification must be consistent with SBI's FDA establishment registration (Delaware File No. 7834291) and Part 807 registration and listing information.
B. Rx Only Statement (21 C.F.R. § 801.109)
Deficiency: The "Rx Only" legend is present on the outer carton labeling for both the C14 Sensor and the R7 Reader; however, the legend is absent from the IFU title page and from the physician labeling cover page. Under 21 C.F.R. § 801.109(b)(1), a prescription device must bear the statement "Caution: Federal law restricts this device to sale by or on the order of a _" or, alternatively, the symbol "Rx only" on all labeling. The omission of this statement from the IFU and physician labeling constitutes a misbranding violation and would likely be identified by FDA during review of the 510(k) submission.
Recommendation: The "Rx Only" legend (or the alternative "℞ only" symbol) should be added in a prominent position on the following labeling components:
(i) The IFU title page, in a conspicuous location adjacent to or immediately below the device name;
(ii) The physician labeling cover page, in a location consistent with the placement on other labeling components;
(iii) Any additional labeling materials (e.g., quick start guides, patient training materials) that may be developed for the U.S. market.
The legend should be in a font size consistent with the requirements of § 801.15 for prominence and conspicuousness.
C. Unique Device Identification (UDI) Compliance
Deficiency: The draft labeling does not include the Unique Device Identifier (UDI) in either the human-readable format (plain text) or the machine-readable format (AIDC, such as a barcode) on the device label or device package. Additionally, we understand that Solstice has not yet obtained the U.S.-specific Global Trade Item Number (GTIN) / Device Identifier (DI) assignments necessary for UDI compliance in the U.S. market. The current labeling contains only the EU-format identifiers, which are not compliant with the FDA's UDI requirements under 21 C.F.R. Part 830.
Recommendation: Solstice should take the following steps to achieve UDI compliance:
(i) Obtain a U.S.-specific UDI from an FDA-accredited issuing agency (GS1, HIBCC, ICCBBA, or ISBT 128). We recommend GS1 for consistency with existing Solstice product identification practices, but this determination should be made by the Solstice supply chain and regulatory affairs teams.
(ii) Ensure that the UDI appears in both human-readable and machine-readable (AIDC) format on: (a) the device label (for the C14 Sensor, this would be the individual sensor pouch label; for the R7 Reader, this would be the device itself or the label affixed thereto); (b) the device package (outer carton for both C14 Sensor pack and R7 Reader); and (c) at any higher level of packaging used for shipping or distribution.
(iii) Submit the required device information (device description, company name, brand name, model number, version or model, labeler DUNS number, and other required data elements) to the FDA's Global Unique Device Identification Database (GUDID) prior to marketing the device in the United States.
(iv) Ensure that the Production Identifier (PI) elements—including lot or batch number, expiration date, manufacturing date (if applicable), and distinct identification code (serial number for the R7 Reader)—are correctly formatted and applied in accordance with 21 C.F.R. Part 830 requirements.
D. EU-Specific References to Be Removed or Modified
Deficiency: The draft labeling contains multiple references to EU-specific regulatory elements that are not applicable to the U.S. market and, if retained, could create confusion for U.S. users and raise misbranding concerns. Specific EU-specific references identified in our review include:
(i) The CE marking symbol (CE 0483), which appears on the outer carton, inner carton, IFU cover page, and physician labeling cover page;
(ii) References to the EU Medical Device Regulation (Regulation (EU) 2017/745) in the regulatory information sections of the IFU and physician labeling;
(iii) Identification of Meridian Conformity Assessment GmbH as the notified body, including the notified body number (NB 0483);
(iv) References to the Summary of Safety and Clinical Performance (SSCP) document required under EU MDR Article 32, including a URL link to the EUDAMED database entry;
(v) References to the European Authorized Representative and the EU importer, which are EU MDR-specific requirements.
Recommendation: C&H strongly recommends that Solstice prepare separate U.S.-specific labeling rather than attempting to create combined global labeling. Combined labeling (i.e., a single labeling document containing both EU and U.S. regulatory information in separate sections) is technically permissible but introduces significant risks: it increases the potential for user confusion, makes the labeling more complex and difficult to maintain, and may invite FDA scrutiny regarding the prominence and clarity of U.S.-specific information. If Solstice elects to pursue combined global labeling despite this recommendation, the U.S.-specific content must be clearly delineated from EU content—for example, through a separate, clearly labeled U.S. regulatory information section—and all U.S. required elements must appear prominently and not be overshadowed by EU-specific information.
If separate U.S. labeling is prepared (the recommended approach), all EU-specific references should be removed entirely from the U.S. labeling package.
E. Language and Readability
Deficiency: Several sections of the draft labeling employ British English spelling conventions, consistent with the labeling's origin as an adaptation of the EU MDR labeling prepared by SBD's Dublin-based regulatory affairs team. Examples identified in our review include:
• "colour" (should be "color")
• "metre" (should be "meter")
• "behaviour" (should be "behavior")
• "recognise" (should be "recognize")
• "calibre" (should be "caliber")
• "programme" (should be "program")
• "centre" (should be "center")
• "analyse" (should be "analyze")
• "catalogue" (should be "catalog")
• "defence" (should be "defense")
Additionally, certain measurement units are expressed solely in SI units without U.S. customary equivalents where such equivalents would be expected by U.S. users. While SI units are generally acceptable and preferred for scientific measurements, glucose values are conventionally reported in mg/dL in U.S. clinical practice (as opposed to mmol/L, which is common in many other countries). The draft labeling correctly uses mg/dL as the primary unit for glucose values in most locations, but we identified three instances where mmol/L appears as the primary unit or where mg/dL equivalents are omitted.
Recommendation: The entire labeling package should be reviewed and converted to American English spelling conventions throughout. Glucose values should appear consistently in mg/dL as the primary unit, consistent with U.S. clinical practice and the conventions used in the labeling of the identified predicate devices. The measurement range of 40–400 mg/dL should be stated consistently across all labeling components. Where dual units are provided for glucose values (mg/dL and mmol/L), mg/dL should appear first, with mmol/L in parentheses, if included at all.
V. Indications for Use / Intended Use Statement
A. Current Draft Language Review
The draft labeling states the intended use of the Lumina CGM System as follows:
"The Solstice Lumina™ Continuous Glucose Monitoring System is intended for the continuous monitoring of glucose levels in the interstitial fluid of persons with diabetes mellitus. The system is indicated for use in adults and children aged 4 years and older."
This language reflects the EU-approved indication as established under CE certificate MCA-2024-07319. However, the U.S. intended use must be limited to the indication that will be supported by the planned 510(k) submission and the LUMINA-US clinical study.
Deficiency: The intended use statement in the draft labeling includes a patient population—"adults and children aged 4 years and older"—that is broader than the population that will be studied in the LUMINA-US clinical trial (Protocol SBD-LUM-CL-001), which enrolls only subjects aged 18 years and older with Type 1 or Type 2 diabetes mellitus. Additionally, the draft intended use does not specify the types of diabetes mellitus for which the device is indicated, whereas the LUMINA-US study and the identified predicate devices are specific to Type 1 and Type 2 diabetes.
Recommendation: The intended use statement should be revised to read substantially as follows:
"The Solstice Lumina™ Continuous Glucose Monitoring System is intended for continuously monitoring glucose levels in the interstitial fluid of persons aged 18 years and older with Type 1 or Type 2 diabetes mellitus. The Lumina CGM System is a prescription device."
The precise wording of the intended use statement must match the Indications for Use Statement that will be submitted on FDA Form 3881 as part of the 510(k) submission. Any discrepancy between the labeling and the FDA Form 3881 statement may result in a Refuse to Accept (RTA) determination by FDA or an Additional Information (AI) request during the substantive review, either of which would delay the clearance timeline. C&H recommends that the Indications for Use statement on Form 3881 be finalized as early as practicable—ideally in connection with the Pre-Sub meeting—and that all labeling components be updated to reflect that finalized language verbatim.
B. Consistency with Predicate Indications
Maintaining consistency with the indications for use of the identified predicate devices is a critical element of the substantial equivalence argument that will underpin the 510(k) submission. The primary predicate device, the NovaSense GlucoTrack NX-500 (510(k) No. K211034), and the secondary predicate device, the NovaSense GlucoTrack NX-700 (510(k) No. K230489), are both limited to adults aged 18 years and older. The Lumina CGM System's labeling must not broaden the intended use population beyond what is supported by the substantial equivalence argument and the clinical data that will be generated in the LUMINA-US study. Any expansion of the intended use population—for example, to include pediatric patients—would require additional clinical data and would likely necessitate a separate 510(k) submission or a de novo classification request, as a broader indication would undermine the substantial equivalence comparison with the identified predicates.
C. Prescription Use Statement
Both the IFU and the physician labeling should clearly state that the Lumina CGM System is a prescription device, intended for use only by or on the order of a licensed healthcare practitioner. The labeling should further specify that sensor insertion and initial system setup require either a healthcare professional or a patient/caregiver who has been trained in the insertion procedure in accordance with the prescriber's instructions. This clarification is important to ensure that the device is used safely and within the scope of its intended use, and to avoid potential liability exposure from use by untrained individuals.
VI. Warnings and Precautions
The warnings and precautions sections of the draft labeling are among the areas requiring the most substantial revision for U.S. compliance. FDA expects CGM device labeling to contain comprehensive, specific warnings and precautions that address the reasonably foreseeable risks associated with device use. The draft labeling, adapted from the EU MDR version, is incomplete in several respects and, in certain cases, insufficiently specific. The following deficiencies and recommendations are organized by topic.
A. Identified Deficiencies in Warnings
1. Adjunctive vs. Non-Adjunctive Use Warning. Deficiency: The draft labeling is ambiguous regarding whether the Lumina CGM System is intended for adjunctive use—requiring confirmatory fingerstick blood glucose testing before treatment decisions are made—or non-adjunctive use—permitting treatment decisions, including insulin dosing, to be made based solely on CGM readings without confirmatory fingerstick testing. The draft IFU contains language in one section stating that "users should confirm glucose readings with a blood glucose meter before making treatment decisions" (Section 7.2, p. 34), while another section states that "the Lumina CGM System provides real-time glucose data to support diabetes management decisions" (Section 2.1, p. 8) without any qualification regarding the need for confirmatory testing. This inconsistency creates significant patient safety and regulatory compliance concerns.
Recommendation: The adjunctive versus non-adjunctive use determination is among the most consequential labeling decisions for the Lumina CGM System and has direct implications for the device's classification and the scope of the 510(k) submission. C&H recommends the following approach:
(a) If Solstice seeks non-adjunctive labeling (consistent with iCGM classification under DEN170088), the labeling must: (i) clearly state that the Lumina CGM System may be used to make diabetes treatment decisions without a confirmatory fingerstick test; (ii) specify the clinical performance thresholds that support this claim, including the demonstrated MARD of ≤ 9.0%; and (iii) include a warning identifying the specific circumstances under which confirmatory fingerstick testing is still recommended, such as when symptoms do not match CGM readings, during periods of rapidly changing glucose concentrations, when the system displays a signal loss or communication error, or when the system indicates glucose values at the extremes of the measurement range.
(b) If Solstice seeks adjunctive labeling, the labeling must include a prominent warning—in both the IFU and the physician labeling—stating that treatment decisions, including insulin dosing decisions, should not be made based solely on CGM readings and that a confirmatory blood glucose test using an FDA-cleared blood glucose monitoring system is required before making treatment decisions.
(c) Regardless of the determination, the labeling must be internally consistent. All references to the role of CGM readings in treatment decisions must align with the adjunctive or non-adjunctive claim.
This issue should be included in the Pre-Sub meeting questions for FDA (see Section XVI below), and the labeling should be held in draft form with respect to the adjunctive/non-adjunctive determination until FDA feedback is received.
2. MRI Safety Warning. Deficiency: The C14 implantable sensor contains metallic components, specifically a platinum-iridium (PtIr) electrode, which raises MRI safety concerns. The draft labeling includes an MRI conditional statement—"MR Conditional: The Lumina C14 sensor has been tested and found to be MR Conditional under specified conditions"—but critically fails to specify the conditions under which MRI is safe. Specifically, the draft labeling does not identify: the maximum static magnetic field strength (e.g., 1.5T, 3T); the maximum spatial gradient field; the maximum whole-body specific absorption rate (SAR); the maximum allowable scan duration; or any anatomical placement restrictions relative to the MRI coil.
Recommendation: This is a critical patient safety issue. The MRI safety labeling must be revised to include complete MRI conditional information in accordance with the ASTM F2503 standard and the FDA's guidance on MRI safety labeling. Specifically, the labeling should include:
(a) A clear statement of MRI conditional status, including the specific conditions under which MRI may be safely performed with the sensor in situ. These conditions must be based on MRI safety testing data. If MRI conditional testing has been completed, the specific parameters (field strength, gradient, SAR limits, scan duration, sensor placement considerations) must be stated.
(b) If MRI conditional testing has not been completed or does not support MRI conditionality, the labeling must instead include a warning that the C14 Sensor must be removed prior to undergoing any MRI procedure and that MRI safety has not been established for the device.
(c) In either case, the MRI safety warning must appear prominently in both the patient IFU (in language understandable to lay users) and the physician labeling. The warning should be highlighted through visual emphasis (e.g., bold text, warning icon, shaded box) to ensure it is not overlooked.
(d) C&H recommends that Solstice coordinate with Dr. Aisling Burke (CTO) and the SBD engineering team to confirm the current status of MRI conditional testing and to provide the specific parameters necessary for labeling purposes. If testing is not yet complete, the testing timeline should be established promptly, as MRI safety labeling is a critical component that must be finalized before the 510(k) submission.
3. CT/X-Ray and Other Imaging Modalities. Deficiency: The draft labeling does not contain any warning or precaution regarding the use of CT scans, X-rays, or other medical imaging modalities in patients wearing the C14 Sensor. Given that the sensor is implanted subcutaneously and contains metallic components, there is a reasonable potential for imaging artifacts that could interfere with diagnostic image interpretation. Additionally, certain imaging modalities (e.g., high-energy radiation therapy) could potentially damage the sensor or affect its function.
Recommendation: Add a warning in both the IFU and physician labeling stating that: (i) the C14 Sensor may produce artifacts on CT, X-ray, or other medical images, which could interfere with image interpretation; (ii) patients should inform imaging technicians and radiologists about the presence and location of the sensor prior to any imaging procedure; and (iii) if there is any concern about potential interference with an imaging study, the sensor should be removed prior to the procedure at the discretion of the treating healthcare professional.
4. Interference Substances Warning. Deficiency: The list of substances known or expected to interfere with the accuracy of CGM glucose readings is materially incomplete in the draft labeling. The draft mentions only acetaminophen (paracetamol) as a potential interferent. FDA's expectations for CGM labeling, as reflected in the September 2023 iCGM guidance and in the labeling of predicate devices, require disclosure of all substances that have been tested for interference and all substances known to cause clinically significant interference with the glucose measurement.
Recommendation: The interfering substances warning should be expanded to include all substances tested during interference testing conducted at Whitmore Laboratories Inc. At a minimum, the following substances should be addressed in the labeling (with specific information regarding whether clinically significant interference was observed or was not observed at tested concentrations):
• Acetaminophen (paracetamol)
• Ascorbic acid (vitamin C)
• Salicylic acid
• Dopamine
• Ibuprofen
• Tolbutamide
• Tetracycline
• Uric acid
• Bilirubin
• Triglycerides
• Hematocrit variations
• Hydroxyurea (if tested)
• Mannitol (if tested)
The specific list of tested substances should be confirmed with Pinnacle and the Whitmore Laboratories testing protocols. For any substances found to cause clinically significant interference, the labeling should include a specific warning describing the nature and magnitude of the interference and recommending confirmatory fingerstick blood glucose testing when the patient has recently ingested or been administered the interfering substance.
5. Sensor Wear Duration Warning. Deficiency: The draft labeling warns that the C14 Sensor "should not be worn longer than 14 days" but does not adequately explain the specific risks associated with extended sensor wear beyond the validated wear period. The warning is stated in a single sentence without elaboration.
Recommendation: The sensor wear duration warning should be enhanced to include the following elements:
(a) A clear statement that the C14 Sensor has been validated for a continuous wear period of 14 days (336 hours) and that sensor accuracy and reliability have not been established beyond this period.
(b) A description of the specific risks associated with extended wear, including: (i) increased risk of local skin infection at the insertion site; (ii) potential for degradation of sensor accuracy and unreliable glucose readings; (iii) potential for sensor migration from the original insertion position; and (iv) increased risk of skin irritation, including contact dermatitis, at the adhesive site.
(c) An instruction to remove the sensor promptly at the end of the 14-day wear period and not to attempt to reuse or reinsert the sensor.
6. Altitude, Temperature, and Environmental Conditions. Deficiency: The draft labeling does not contain any warning or precaution regarding device performance at extreme altitudes, temperatures, or humidity levels. The Lumina CGM System's operating specifications—including the operating temperature range, humidity range, and altitude range—are not disclosed in the warnings section or elsewhere in the patient-facing IFU.
Recommendation: The labeling should include:
(a) A clear statement of the device's validated operating environmental specifications, including operating temperature range (e.g., 50°F to 113°F / 10°C to 45°C), operating humidity range (e.g., 10% to 93% relative humidity, non-condensing), and operating altitude range (e.g., -1,200 ft to 12,000 ft / -366 m to 3,658 m), or whatever specifications are supported by the device's environmental testing data.
(b) A warning that the device may not function accurately or reliably outside of its specified operating environment and that users should avoid exposing the device to extreme heat, cold, or humidity.
(c) A note regarding storage conditions for the C14 Sensor, including recommended storage temperature range and the consequences of exposure to temperatures outside the recommended range (e.g., sensor damage, reduced shelf life, potential for inaccurate readings).
B. Identified Deficiencies in Precautions
1. Pediatric Use Precaution. Deficiency: The draft labeling does not include a statement that the safety and effectiveness of the Lumina CGM System have not been established in patients under 18 years of age. Given that the EU-approved indication includes children aged 4 years and older but the U.S. intended use will be limited to adults aged 18 years and older, it is essential that the U.S. labeling include a clear precaution regarding the absence of pediatric data.
Recommendation: Add a precaution to the IFU and physician labeling stating: "Safety and effectiveness of the Lumina CGM System have not been established in individuals under 18 years of age. The device is not intended for use in the pediatric population." This precaution is consistent with the planned 510(k) submission scope and the LUMINA-US study population, which enrolls only adults aged 18 years and older.
2. Pregnancy and Gestational Diabetes. Deficiency: The draft labeling does not contain any precaution regarding use of the Lumina CGM System in pregnant patients or in patients with gestational diabetes mellitus (GDM). Pregnancy can alter glucose metabolism and interstitial fluid dynamics, potentially affecting CGM accuracy. Additionally, the LUMINA-US study excludes pregnant patients from enrollment.
Recommendation: Add a precaution stating: "The Lumina CGM System has not been evaluated in pregnant patients. Accuracy of the device during pregnancy has not been established. Patients with gestational diabetes mellitus should consult their healthcare provider before using this device."
3. Critically Ill Patients. Deficiency: The draft labeling does not include a precaution regarding the use of the Lumina CGM System in critically ill patients, hospitalized patients, or patients undergoing dialysis. These patient populations may present physiological conditions (e.g., hypoperfusion, edema, fluid shifts) that affect interstitial fluid glucose concentrations and, consequently, CGM accuracy. The LUMINA-US clinical study is designed for ambulatory patients and does not enroll critically ill, ICU, or dialysis patients.
Recommendation: Add a precaution stating: "The Lumina CGM System is intended for use in ambulatory settings and has not been evaluated in critically ill, intensive care unit (ICU), or dialysis patient populations. The accuracy and reliability of the device in these settings have not been established. The device should not be used as the sole basis for glucose monitoring in critically ill patients."
4. Electromagnetic Interference. Deficiency: The draft labeling includes a generic precaution regarding electromagnetic interference ("Keep the device away from strong electromagnetic fields") but does not reference the specific wireless communication technology used by the Lumina CGM System (BLE 5.2) or the potential sources of interference that could affect the BLE connection between the C14 Sensor and the R7 Reader. The precaution is insufficiently specific to be meaningful to users.
Recommendation: Revise the electromagnetic interference precaution to:
(a) Identify the BLE 5.2 wireless communication protocol used for data transmission between the C14 Sensor and the R7 Reader;
(b) Note that strong electromagnetic fields, certain electronic devices, or environments with high radio frequency interference may disrupt the BLE 5.2 connection and result in temporary loss of glucose data transmission;
(c) Reference the results of electromagnetic compatibility (EMC) testing conducted at Whitmore Laboratories Inc. (to the extent appropriate for inclusion in patient-facing labeling) or, at a minimum, state that the device has been tested for EMC in accordance with applicable standards; and
(d) Provide practical guidance for users, such as maintaining the recommended proximity between the C14 Sensor and R7 Reader and being aware that certain environments (e.g., airport security screening areas, certain industrial settings) may cause temporary communication disruptions.
VII. Contraindications
A. Current Draft Review
The draft labeling lists two contraindications for the Lumina CGM System:
1. Patients with known allergy to sensor adhesive materials.
2. Patients unable to maintain minimum sensor body clearance from transmitter.
Deficiency: This list is incomplete for the U.S. market and does not meet FDA's expectations for comprehensive contraindication labeling for CGM devices. The contraindication regarding "minimum sensor body clearance from transmitter" is vaguely worded and does not convey a specific clinical condition or patient characteristic. Additionally, several clinically important contraindications applicable to the Lumina CGM System are absent.
B. Recommended Additional Contraindications
Based on our review of FDA's expectations for CGM device labeling, the labeling of predicate devices, and the specific technological and clinical characteristics of the Lumina CGM System, C&H recommends that the following additional contraindications be included:
1. Hypersensitivity to sensor materials. Patients with known hypersensitivity to platinum, iridium, or other materials used in the C14 Sensor (specifically the PtIr-4G electrode coating) should be listed as contraindicated. This contraindication is distinct from allergy to the adhesive materials and addresses a different risk.
2. Pediatric patients. Use in patients under 18 years of age should be listed as a contraindication, consistent with the intended use limitation and the absence of pediatric clinical data.
3. MRI procedures. If MRI conditional testing has not been completed or does not support MRI conditionality under specified parameters, the labeling should contraindicate use during MRI procedures. The contraindication should state that the C14 Sensor must be removed prior to MRI.
4. Dialysis and severe dehydration. If clinical data does not support the use of the Lumina CGM System in patients undergoing dialysis or experiencing severe dehydration (conditions that can significantly alter interstitial fluid glucose concentrations), these populations should be listed as contraindicated for device use.
5. Use with unvalidated AID systems. The labeling should contraindicate the use of the Lumina CGM System for dosing decisions with automated insulin delivery (AID) systems unless the device has been specifically validated and cleared by FDA for interoperability with such systems. This is a particularly important contraindication in the context of iCGM classification, as iCGM devices may be marketed for interoperability with compatible AID systems, but such interoperability must be validated for each specific AID system. If the Lumina CGM System has not been validated for use with any specific AID system at the time of the 510(k) submission, the contraindication should clearly state this limitation.
C&H further recommends that the existing contraindication regarding "minimum sensor body clearance from transmitter" be revised for clarity. The intended meaning of this contraindication is unclear, and it should be either reworded to describe a specific clinical condition or anatomical limitation (e.g., patients with insufficient subcutaneous tissue depth at the intended insertion site) or removed if it does not address a genuine contraindication.
VIII. Sensor Insertion Instructions (IFU)
The sensor insertion instructions are a critical component of the IFU from both a user safety and a regulatory compliance perspective. Errors or omissions in the insertion instructions can lead to serious adverse events, including infection, inaccurate glucose readings due to improper sensor placement, and physical injury to the patient. Our review of the draft sensor insertion instructions identified the following deficiencies.
A. Identified Deficiencies
1. Anatomical Site Specification. Deficiency: The draft IFU refers to "the abdomen or upper arm" as the approved insertion sites for the C14 Sensor. However, the LUMINA-US clinical study protocol (SBD-LUM-CL-001) evaluates only the upper arm as the primary insertion site. Moreover, the primary predicate device (NovaSense GlucoTrack NX-500, K211034) is cleared for abdomen use only, while the secondary predicate device (NovaSense GlucoTrack NX-700, K230489) is cleared for both abdomen and upper arm. This creates a complex regulatory situation that must be carefully navigated in the labeling.
Recommendation: The labeled insertion site(s) must be restricted to only those anatomical sites for which clinical validation data supports the accuracy and safety of the device. The following approach is recommended:
(a) If the LUMINA-US study evaluates only the upper arm, the U.S. labeling should be limited to the upper arm as the sole approved insertion site. Including the abdomen as an insertion site in the absence of U.S. clinical data from the abdomen could be viewed by FDA as an unsupported labeling claim.
(b) If Solstice wishes to include the abdomen as an approved insertion site in the U.S. labeling, additional clinical data demonstrating sensor accuracy and safety at the abdominal site may be required. This could potentially be addressed through a protocol amendment to the LUMINA-US study or through a separate study, but either approach would have timeline and resource implications.
(c) This issue should be discussed with FDA during the Pre-Sub meeting (August 14, 2025) to obtain FDA's guidance on the acceptability of labeling the upper arm alone, the potential to rely on predicate data for the abdominal site, or the need for additional clinical data.
2. Sensor Insertion Procedure Illustrations. Deficiency: The sensor insertion illustrations in the draft IFU depict a three-step insertion process (open package, position applicator, press to insert) but omit two important procedural steps. First, the illustrations do not include a skin preparation step (i.e., cleaning and disinfecting the insertion site prior to sensor placement). Second, the illustrations do not depict or describe the post-insertion sensor activation and warm-up procedure, during which no glucose readings are available.
Recommendation: The sensor insertion instructions should be revised to include the following additional illustrated steps:
(a) Skin preparation step: Prior to sensor insertion, the insertion site should be cleaned with an appropriate antiseptic agent (e.g., isopropyl alcohol wipe). The labeling should include an illustration showing the skin being cleaned and allowed to dry before the applicator is positioned.
(b) Sensor warm-up step: Following insertion, the sensor requires a warm-up period of up to 60 minutes during which sensor equilibration occurs and no glucose readings are available to the user. The labeling should include an illustration or screen depiction showing the warm-up countdown on the R7 Reader or the Lumina Mobile App, along with an explanation that glucose readings will not be available during this period and that the user should not make treatment decisions based on any readings displayed during the warm-up.
(c) R7 Reader placement: An illustration should be added showing the proper placement of the R7 Reader over or adjacent to the sensor insertion site to initiate communication between the sensor and the reader, including the recommended proximity distance.
3. Sensor Removal and Disposal. Deficiency: The instructions for sensor removal in the draft IFU are brief—consisting of only two sentences—and do not adequately address sharps disposal requirements or biohazard handling procedures. Given that the C14 Sensor is a subcutaneously implanted device with a sharp insertion element, proper disposal guidance is essential for user safety and regulatory compliance.
Recommendation: The sensor removal section should be expanded to include:
(a) Detailed step-by-step instructions for removing the sensor from the skin, including guidance on gently peeling the adhesive and withdrawing the sensor from the subcutaneous tissue.