(37 days)
iSage Rx is indicated for use by adult patients with type 2 diabetes, and by their healthcare providers to provide ongoing support for understanding and following a titration plan for the following medications, with the goal of reaching optimal medication dose and/or target fasting blood sugar control:
-Basal insulins
-Combinations of basal insulin and GLP-1 receptor agonists
iSage Rx System includes a web-based, HIPAA-compliant, password protected Health Care Provider (HCP), Account Administrated websites, and a patient mobile app. The system was designed to enable HCPs to digitize and deploy their basal insulin titration plan such that adult patients with type 2 diabetes may better understand and follow their basal insulin treatment plan through the iSage Rx app. The iSage Rx patient app is a stand-alone, prescription-use only (Rx-only) software device for use under the direction of a healthcare provider, that has the capability to titrate basal insulin and medications that combine basal insulin and GLP-1 receptor agonists, via rule-based protocols as part of a Titration Plan ordered by a Health Care Provider (HCP). It is intended for use in type 2 diabetes in a nonacute care setting.
The primary purpose of the iSage Rx device is to help the patient safely reach their fasting blood glucose targets and reach a maintenance dose of insulin through regular monitoring of blood glucose levels and titration of insulin doses.
This document is a 510(k) summary for the iSage Rx Platform. It details the device's intended use, comparison to a predicate device, and performance data to demonstrate substantial equivalence.
Here's a breakdown of the requested information based on the provided text:
1. A table of acceptance criteria and the reported device performance
The document does not explicitly present a table of acceptance criteria with corresponding performance metrics in a pass/fail format. Instead, it relies on the concept of "substantial equivalence" to a predicate device (iSage Rx, K161865). The performance data section describes "Software Verification and Validation Testing" that was conducted to demonstrate the device performs as intended and meets identified requirements.
However, based on the document's content, we can infer some implicit acceptance criteria:
| Acceptance Criteria (Inferred) | Reported Device Performance |
|---|---|
| Functional Equivalence to Predicate Device | The iSage Rx Platform's "purpose, design, function, and intended use... is identical to the predicate device." The "iSage Rx Platform contains all functionality of iSage Rx and Dose Check products." "iSage Rx includes all available feature configurations, whereas Dose Check contains only those features configured for a specific geography." Software verification and validation testing were conducted, and documentation was provided, to demonstrate the effectiveness of design control mitigations for identified risks. The "Traceability Matrix for iSage Rx Platform displays a matrix of all requirements by type and ID along with the related individual verification and validation test cases demonstrating that the requirement has been satisfied." The device "will perform as intended under specified use conditions." |
| Safety and Effectiveness Equivalence to Predicate Device | "Having no significant differences from the predicate device, it is therefore concluded that the iSage Platform has a similar safety and effectiveness profile and is substantially equivalent." "The non-clinical data affirms the device's safety." |
| Accuracy of Dose Calculation | The device is a "Predictive Pulmonary-Function Value Calculator" (Regulation Name) and "Calculator, Drug Dose" (Device Classification Name). The "Device Description" states its primary purpose is "to help the patient safely reach their fasting blood glucose targets and reach a maintenance dose of insulin through regular monitoring of blood glucose levels and titration of insulin doses." The system "calculates a fasting blood glucose average and generates an insulin dose according to the prescribed titration plan." The performance data section mentions "nonclinical datasets in the form of testing protocols and reports" that summarize "verification and validation of the key design requirements associated with safety and performance." This implicitly covers the accuracy of dose calculations as a critical safety and performance aspect, although specific metrics (e.g., calculation deviation) are not provided. |
| Interoperability with Supported Glucose Meters | "The iSage Rx Platform is interoperable with supported glucose meters noted in table 3 below. This interoperability is substantially equivalent to that of the predicate device in terms of the functionality enabling Bluetooth connections between the glucose meter and the device (K161865)." The document lists specific supported models (e.g., CONTOUR® NEXT ONE, Accu-Chek® Guide). "Integration with the following devices is supported by the iSage Rx device." |
| Compliance with Regulatory Standards | "All product development activities for the iSage Rx Platform were conducted in compliance with EN ISO 13458:2016 under the quality management system that has been certified by Intertek Medical Notified Body AB (Certificate Number:0139273)." "Software verification and validation testing were conducted, and documentation was provided as recommended by FDA's Guidance for Industry and FDA Staff, 'Content of Premarket Submissions for Device Software Functions.'" |
| Cybersecurity | "Cybersecurity Information" is listed as a labelling information item, implying that this was addressed as part of the overall evaluation. |
| User Interface and Experience | The "Device Description" mentions that the "iSage Rx patient app is a stand-alone, prescription-use only (Rx-only) software device for use under the direction of a healthcare provider, that has the capability to titrate basal insulin and medications that combine basal insulin and GLP-1 receptor agonists, via rule-based protocols..." "The iSage Rx Platform contains all functionality of iSage Rx and Dose Check products. iSage Rx/Dose Check is localized to the USA and contains a set of features, configured specifically for this particular geography based on market configurations." The patient app "prompts the patient every day to record their fasting blood glucose measurements and daily insulin doses." "If enough blood glucose information has not been recorded by the patient, the dose is not changed, and the patient is informed why the dose hasn't changed and is reminded to record their fasting blood glucose values." This indicates user flow and messaging were tested and met expectations. Dose Check is noted to have "identical in function, with the difference in the user interface only." |
2. Sample size used for the test set and the data provenance (e.g., country of origin of the data, retrospective or prospective)
The document refers to "Software Verification and Validation Testing" and "nonclinical datasets in the form of testing protocols and reports." However, it does not specify the sample size of the test set, nor does it specify the data provenance (country of origin, retrospective or prospective). It mentions that "All product development activities for the iSage Rx Platform were conducted in compliance with EN ISO 13458:2016," but this refers to the quality management system, not the specifics of the data used for testing. The product is localized to the USA for specific configurations.
3. Number of experts used to establish the ground truth for the test set and the qualifications of those experts (e.g. radiologist with 10 years of experience)
The document does not provide information on the number or qualifications of experts used to establish ground truth for the test set. It mentions the "Healthcare Provider (HCP) portal" and HCPs configuring titration plans, implying medical expertise is involved in the overall system, but not specifically for the ground truth of the validation testing.
4. Adjudication method (e.g. 2+1, 3+1, none) for the test set
The document does not specify any adjudication method for the test set.
5. If a multi reader multi case (MRMC) comparative effectiveness study was done, If so, what was the effect size of how much human readers improve with AI vs without AI assistance
This document describes a software device that provides a titration plan for patients with type 2 diabetes. It is a standalone software device intended for patient and HCP use to manage medication dosage, not an AI-assisted diagnostic tool for human readers interpreting medical images. Therefore, an MRMC comparative effectiveness study involving human readers improving with AI assistance would not be applicable in this context. The document focuses on the software's functional accuracy and safety in calculating and presenting drug doses.
6. If a standalone (i.e. algorithm only without human-in-the-loop performance) was done
Yes, a form of standalone performance evaluation was implicitly done for the algorithm. The "Software Verification and Validation Testing" and "nonclinical datasets" would involve testing the algorithm's output against expected results based on predefined rules for titration plans. The device's function is to "calculate a fasting blood glucose average and generates an insulin dose according to the prescribed titration plan." This is an algorithmic function that would be tested independently of patient or HCP interaction to confirm its computational accuracy.
7. The type of ground truth used (expert consensus, pathology, outcomes data, etc)
The document strongly implies that the "ground truth" for the device's dose calculation and titration logic is established based on "evidence-based preset clinical titration plans" and "evidence-based protocols from treat-to-target studies or other patient-led titration studies." HCPs can also create their own plans or customize these, further indicating that the ground truth is derived from established medical guidelines and clinical evidence for diabetes treatment. While not explicitly stated as "expert consensus" for the test set itself, the underlying principle is rooted in validated clinical practice.
8. The sample size for the training set
The document describes software that applies rule-based protocols for dose titration. It does not mention a training set or machine learning components that would require a "training set sample size" in the context of predictive algorithms that learn from data. The device operates on "rule-based protocols."
9. How the ground truth for the training set was established
As the device operates on "rule-based protocols" and does not appear to use machine learning from a training set, the concept of establishing ground truth for a training set is not applicable here. The "ground truth" for the rules themselves would be derived from clinical guidelines and evidence as mentioned in point 7.
{0}------------------------------------------------
Image /page/0/Picture/0 description: The image contains the logo of the U.S. Food and Drug Administration (FDA). The logo consists of two parts: the Department of Health & Human Services logo on the left and the FDA acronym with the full name of the agency on the right. The FDA part of the logo is in blue, with the acronym in a square and the full name written out to the right of the square.
August 21, 2024
Amalgam Rx, Inc Andy Miller VP, Reg. & Quality 1007 N. Orange St., Ste.400 Wilmington, Delaware 19801
Re: K242066
Trade/Device Name: iSage Rx Regulation Number: 21 CFR 868.1890 Regulation Name: Predictive Pulmonary-Function Value Calculator Regulatory Class: Class II Product Code: NDC Dated: July 15, 2024 Received: July 15, 2024
Dear Andy Miller:
We have reviewed your section 510(k) premarket notification of intent to market the device referenced above and have determined the device is substantially equivalent (for the indications for use stated in the enclosure) to legally marketed predicate devices marketed in interstate commerce prior to May 28, 1976, the enactment date of the Medical Device Amendments, or to devices that have been reclassified in accordance with the provisions of the Federal Food, Drug, and Cosmetic Act (the Act) that do not require approval of a premarket approval application (PMA). You may, therefore, market the device, subject to the general controls provisions of the Act. Although this letter refers to your product as a device, please be aware that some cleared products may instead be combination products. The 510(k) Premarket Notification Database available at https://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfpmn/pmn.cfm identifies combination product submissions. The general controls provisions of the Act include requirements for annual registration, listing of devices, good manufacturing practice, labeling, and prohibitions against misbranding and adulteration. Please note: CDRH does not evaluate information related to contract liability warranties. We remind you, however, that device labeling must be truthful and not misleading.
If your device is classified (see above) into either class II (Special Controls) or class III (PMA), it may be subject to additional controls. Existing major regulations affecting your device can be found in the Code of Federal Regulations, Title 21, Parts 800 to 898. In addition, FDA may publish further announcements concerning your device in the Federal Register.
Additional information about changes that may require a new premarket notification are provided in the FDA guidance documents entitled "Deciding When to Submit a 510(k) for a Change to an Existing Device" (https://www.fda.gov/media/99812/download) and "Deciding When to Submit a 510(k) for a Software Change to an Existing Device" (https://www.fda.gov/media/99785/download).
{1}------------------------------------------------
Your device is also subject to, among other requirements, the Quality System (QS) regulation (21 CFR Part 820), which includes, but is not limited to, 21 CFR 820.30, Design controls; 21 CFR 820.90, Nonconforming product; and 21 CFR 820.100, Corrective and preventive action. Please note that regardless of whether a change requires premarket review, the QS regulation requires device manufacturers to review and approve changes to device design and production (21 CFR 820.30 and 21 CFR 820.70) and document changes and approvals in the device master record (21 CFR 820.181).
Please be advised that FDA's issuance of a substantial equivalence determination does not mean that FDA has made a determination that your device complies with other requirements of the Act or any Federal statutes and regulations administered by other Federal agencies. You must comply with all the Act's requirements, including, but not limited to: registration and listing (21 CFR Part 807); labeling (21 CFR Part 801 and Part 809); medical device reporting of medical device-related adverse events) (21 CFR Part 803) for devices or postmarketing safety reporting (21 CFR Part 4, Subpart B) for combination products (see https://www.fda.gov/combination-products/guidance-regulatory-information/postmarketing-safetyreporting-combination-products); good manufacturing practice requirements as set forth in the quality systems (QS) regulation (21 CFR Part 820) for devices or current good manufacturing practices (21 CFR Part 4, Subpart A) for combination products; and, if applicable, the electronic product radiation control provisions (Sections 531-542 of the Act); 21 CFR Parts 1000-1050.
Also, please note the regulation entitled, "Misbranding by reference to premarket notification" (21 CFR 807.97). For questions regarding the reporting of adverse events under the MDR regulation (21 CFR Part 803), please go to https://www.fda.gov/medical-device-safety/medical-device-reportingmdr-how-report-medical-device-problems.
For comprehensive regulatory information about mediation-emitting products, including information about labeling regulations, please see Device Advice (https://www.fda.gov/medicaldevices/device-advice-comprehensive-regulatory-assistance) and CDRH Learn (https://www.fda.gov/training-and-continuing-education/cdrh-learn). Additionally, you may contact the Division of Industry and Consumer Education (DICE) to ask a question about a specific regulatory topic. See the DICE website (https://www.fda.gov/medical-device-advice-comprehensive-regulatoryassistance/contact-us-division-industry-and-consumer-education-dice) for more information or contact DICE by email (DICE@fda.hhs.gov) or phone (1-800-638-2041 or 301-796-7100).
Sincerely,
Joshua Balsam -S
Joshua M. Balsam, Ph.D. Branch Chief Division of Chemistry and Toxicology Devices OHT7: Office of In Vitro Diagnostics Office of Product Evaluation and Quality Center for Devices and Radiological Health
{2}------------------------------------------------
Indications for Use
| Submission Number (if known) | |
|---|---|
| ------------------------------ | -- |
Device Name
iSage Rx
Indications for Use (Describe)
iSage Rx is indicated for use by adult patients with type 2 diabetes, and by their healthcare providers to provide ongoing support for understanding and following a titration plan for the following medications, with the goal of reaching optimal medication dose and/or target fasting blood sugar control:
-Basal insulins
-Combinations of basal insulin and GLP-1 receptor agonists
Type of Use (Select one or both, as applicable)
Prescription Use (Part 21 CFR 801 Subpart D)
Over-The-Counter Use (21 CFR 801 Subpart C)
CONTINUE ON A SEPARATE PAGE IF NEEDED.
This section applies only to requirements of the Paperwork Reduction Act of 1995.
DO NOT SEND YOUR COMPLETED FORM TO THE PRA STAFF EMAIL ADDRESS BELOW.
The burden time for this collection of information is estimated to average 79 hours per response, including the time to review instructions, search existing data sources, gather and maintain the data needed and complete and review the collection of information. Send comments regarding this burden estimate or any other aspect of this information collection, including suggestions for reducing this burden, to:
Department of Health and Human Services Food and Drug Administration Office of Chief Information Officer Paperwork Reduction Act (PRA) Staff PRAStaff(@fda.hhs.gov
"An agency may not conduct or sponsor, and a person is not required to respond to, a collection of information unless it displays a currently valid OMB number."
{3}------------------------------------------------
510(k) Summary
As required by 21 CFR 807.92 K242066
l. Submitter's Name and Address:
Amalgam Rx, Inc. 1007 N. Orange St., Ste.400 Wilmington, DE 19801
Contact Person:
Andy Miller VP, Regulatory and Quality Amalgam Rx, Inc. +1-210-363-8753
Date Prepared:
Aug 20, 2024
II. Device Information
| Trade/Device Name: | iSage Rx Platform |
|---|---|
| Regulation Name: | Predictive Pulmonary-Function Value Calculator |
| Device Classification Name: | Calculator, Drug Dose |
| Regulatory Number: | 21 CFR 868.1890 |
| Regulatory Class: | II |
| Product Code: | NDC |
lll. Predicate Device
Table 1: Predicate Device
| 510(k) Number | 510(k) Device | Manufacturer |
|---|---|---|
| *K161865 | iSage Rx (iSage Rx Basal InsulinTitration) | iSage Rx, Inc. |
*This predicate device has not been subject to a design related recall No reference devices were used in this submission
IV. Device Description:
iSage Rx and Dose Check
iSage Rx System includes a web-based, HIPAA-compliant, password protected Health Care Provider (HCP), Account Administrated websites, and a patient mobile app. The system was designed to enable HCPs to digitize and deploy their basal insulin titration plan such that adult patients with type 2 diabetes may better understand and follow their basal insulin treatment plan through the iSage Rx app. The iSage Rx patient app is a stand-alone, prescription-use only (Rx-only) software device for use under the direction of a healthcare provider, that has the capability to titrate basal insulin and medications that combine basal insulin and GLP-1 receptor agonists, via rule-based protocols as part
{4}------------------------------------------------
of a Titration Plan ordered by a Health Care Provider (HCP). It is intended for use in type 2 diabetes in a nonacute care setting.
The primary purpose of the iSage Rx device is to help the patient safely reach their fasting blood glucose targets and reach a maintenance dose of insulin through regular monitoring of blood glucose levels and titration of insulin doses.
Prescribing HCPs must register with the iSage Rx system before they can order the Patient Mobile Application. Once the HCP is registered, they may register their patients through the HCP portal, after which the patient receives a link to download the iSage Rx app. As part of the patient registration process, the HCP configures a titration plan specific to that patient.
The HCP can either use the evidence-based preset clinical titration plans available on the HCP portal or create their own. The preset plans are those on-label for a manufacture's drug and/or evidencebased protocols from treat-to-target studies or other patient-led titration studies.
Regardless of the plan chosen, the HCP ultimately defines or approves the following parameters of the titration plan:
-
- Name of supported medication patient has been prescribed.
-
- Starting dose of the supported medication
-
- Target fasting blood glucose range.
-
- Number of units to increase or decrease the supported medication based on an average fasting blood glucose values.
-
- The frequency of the titration (1-7 days)
-
- Hypoglycemia threshold. The default is any blood glucose less than 70 mg/dl, but the HCP may increase that for patients with higher risk of hypoglycemia.
-
- Maximum daily number of units of the supported medication
Once the HCP has completed registering the patient, a text message is sent to the patient's mobile device for the patient to download the app from the App Store or Google Play Store.
After the patient has downloaded the app and onboarded through the registration process, the patient app prompts the patient every day to record their fasting blood glucose measurements and daily insulin doses. On titration day, the app calculates a fasting blood glucose average and generates an insulin dose according to the prescribed titration plan (given that the patient has recorded the required number of sequential daily fasting blood glucose values to calculate an average). From a calculated fasting blood glucose average, the app presents the new dose (if a change is required) on the titration day based on the HCP's titration plan. If enough blood glucose information has not been recorded by the patient, the dose is not changed, and the patient is informed why the dose hasn't changed and is reminded to record their fasting blood glucose values.
Patient data, either manually entered or entered via connected device, are available for view in the provider portal on the Patient Activity screen. Patients are informed of provider updates or changes to the prescribed titration plan through notifications. Using the iSage Rx app may help patients more easily understand their healthcare provider's insulin treatment plan and may help reduce the number of hypoglycemic events.
The iSage Rx Platform contains all functionality of iSage Rx and Dose Check products. iSage Rx/Dose Check is localized to the USA and contains a set of features, configured specifically for this particular
{5}------------------------------------------------
geography based on market configurations. The following functionality are included in the USA released version of the iSage Rx Software platform:
- O Supported medications
- O Supported Clinical Titration Plans
- Supported Wireless glucometers O
- Supported Languages O
- o Supported Hypo-consumables
Dose Check is a white-labeled version of iSage Rx that is identical to iSage Rx. The two software applications are identical in function, with the difference in the user interface only. iSage Rx includes all available feature configurations, whereas Dose Check contains only those features configured for a specific geography.
V. Indications for Use:
iSage Rx is software indicated for use by adult patients with type 2 diabetes, and by their healthcare providers (HCP), who are seeking a digital tool to provide ongoing support for patients to understand and follow their Healthcare Providers' treatment plans for the following medications, with the goal of reaching an optimal dose of medication and/or reaching target fasting blood glucose control:
- Titration of basal insulins
- . Titration of combinations of basal insulin and GLP-1 receptor agonists
Please note that the intended use for the subject device was re-worded for clarity, consistency to the predicate and to include basal + GLP-1 Receptor Agonists as a supported medication. Footnotes were added to specify that age and supported medications listed are configurable by country, and that specific features may or may not be applicable depending on country specific regulatory approvals. These modifications do not alter the overall indications for use or risk profile of the iSage Rx Platform.
VI. Comparison of the Technological Characteristics with the Predicate Device:
The purpose, design, function, and intended use of the iSage Rx Platform and its white-label version Dose Check is identical to the predicate device. The iSage Rx Platform is built based on the latest minor release within iSage Rx 2.0, with minor releases being inclusive of sequential 2.X releases. Minor releases in the 2.X device have included only non-significant changes such as modifying existing functionalities, bug fixes, and minor User Interface updates. All relevant code and documentation shall be used accordingly while allowing for specific configurations, including all Dose Check variants, based on geography.
NOTE: The device, iSage Rx is currently cleared in the United States as a Class II device, Product Code NDC under a 510(k), K161865. However, the device submitted under EU MDR shall be referred to as iSage Rx Platform whose variants are iSage Rx and Dose Check.
{6}------------------------------------------------
The iSage Rx Platform is interoperable with supported glucose meters noted in table 3 below. This interoperability is substantially equivalent to that of the predicate device in terms of the functionality enabling Bluetooth connections between the glucose meter and the device (K161865).
The following are assessment questions and answers used to aid in the assessment of Substantial equivalency:
| Question | Yes | No |
|---|---|---|
| Same Indications for Use Statement? | X | |
| Do differences alter the effect or raise new issues of device safety or effectiveness? | X | |
| Same technological characteristics? | X | |
| Could the new characteristics affect safety or effectiveness? | X | |
| Descriptive characteristics precise enough? | X | |
| New types of safety or effectiveness questions? | X | |
| Accepted scientific methods exist? | X | |
| Performance data available? | X | |
| Data demonstrates equivalence? | X |
Table : SE Assessment Questions and Answers
There are no significant changes in the materials, design, or other features of the iSage Rx Platform as compared with the predicate device.
The following table below show the comparison between the predicate device and the device under the scope of this submission:
| DescriptiveCharacteristic | Predicate Device | Proposed Device | Equivalent |
|---|---|---|---|
| Trade Name | iSage Rx (iSage Rx BasalInsulin Titration) | iSage Rx Platform (iSageRx Basal Insulin Titration) | Same |
| 510(k) Number | K161865 | 510(k) under review | NA |
| ClassificationProduct Code | NDC | NDC | Same |
| DeviceClassificationName | Calculator, Drug Dose(NDC) | Calculator, Drug Dose(NDC) | Same |
| Device Class | Class II | Class II | Same |
Table : Substantially Equivalency Table
{7}------------------------------------------------
| Descriptive | Predicate Device | Proposed Device | Equivalent |
|---|---|---|---|
| Indications forUse | iSage Rx (iSage Rx BasalInsulin Titration) issoftware indicated for useby adult patients aged 21and above who have type2 diabetes and theirhealthcare providers totitrate basal insulin. iSageRx is not intended toreplace the care andmanagement provided bya healthcare professionaltrained in themanagement of diabetes.iSage Rx should not beused by patients withtype 2 diabetes who arealso using prandial insulinor patients with type 1diabetes, gestationaldiabetes, or patientsusing an insulin pump. | iSage Rx Platformsoftware is indicated foruse by adult patients withtype 2 diabetes, and bytheir healthcareproviders (HCP), who areseeking a digital tool toprovide ongoing supportfor patients tounderstand and followtheir HealthcareProviders' treatmentplans for the followingmedications, with thegoal of reaching anoptimal dose ofmedication and/orreaching target fastingblood glucose control:Titration of basalinsulinsTitration ofcombinations ofbasal insulin andGLP-1 receptoragonists | Similar —Differencesinclude:Added "Support forthe Titration ofcombinations ofbasal insulin andGLP-1 receptoragonists" as a newintended use. |
| Intended Use | iSage Rx (iSage Rx Basal | iSage Rx Platform | Similar –Differences |
| Insulin Titration) issoftware indicated for useby adult patients aged 21and above who have type2 diabetes and theirhealthcare providers totitrate basal insulin. iSageRx is not intended toreplace the care andmanagement provided bya healthcare professionaltrained in themanagement of diabetes.ISage Rx should not beused by patients withtype 2 diabetes who arealso using prandial insulinor patients with type 1diabetes, gestationaldiabetes, or patientsusing an insulin pump. | software is indicated foruse by adult patients withtype 2 diabetes, and bytheir healthcareproviders (HCP), who areseeking a digital tool toprovide ongoing supportfor patients tounderstand and followtheir HealthcareProviders' treatmentplans for the followingmedications, with thegoal of reaching anoptimal dose ofmedication and/orreaching target fastingblood glucose control:Titration of basalinsulins Titration ofcombinations ofbasal insulin andGLP-1 receptoragonists Patients using iSage Rxcan record their bloodglucose levels, view theirHealthcare Provider'sdosing plan for supportedmedications, and recordthe medication dosetaken.iSage Rx connects withthe following devices:Glucose metersto transmit BloodGlucose (BG)data | include:Added "Support forthe Titration ofcombinations ofbasal insulin andGLP-1 receptoragonists" as a newintended use. Removedcontraindication forprandial insulin.Removal ofcontraindication foruse of iSageRx/Dose Check thatit "Should not beused by patientswith type 2 diabeteswho are also usingprandial insulin"was removed as itwas intended torefer to titration ofprandial insulin.There are nocontraindications toconcurrent use ofprandial insulin. Itwas deemedunnecessary tospecify acontraindication foreach specific type ofinsulin outside ofthose included inthe intended use. | |
| DescriptiveCharacteristic | Predicate Device | Proposed Device | Equivalent |
| iSage Rx is not intended to replace the care and management provided by a healthcare professional trained in the management of diabetes. iSage Rx should not be used by patients with type 1 diabetes, gestational diabetes, or patients using an insulin pump.Note: The above intended use is applicable to the Dose Check variant as well. | |||
| Device | Description | Description | Similar –Differences |
| The iSage Rx (iSage Rx Basal Insulin Titration) is a stand-alone, Prescription Only (Rx) software system that has the capability to titrate basal insulin, if and when, the prescribing Healthcare Provider (HCP) prescribes the titration schedule.The iSage Rx (iSage Rx Basal Insulin Titration) is comprised of a Mobile application (patient only) and Web-based application for the healthcare provider(s). The applications are called: Healthcare Provider (HCP) Web-based Application Patient Mobile Application Prescribing HCPs must register with the iSage Rx (iSage Rx Basal Insulin Titration) system before they can prescribe the Patient Mobile Application. An iSage Rx, Inc representative will assist the HCP on the phone, or in person, in registering for the portal. The HCP will receive support, including a user guide, on how to use the product to customize and prescribe validated insulin | iSage Rx Platform is a stand-alone, prescription-use only (Rx-only) software device that has the capability to titrate basal insulin and medications that combine basal insulin and GLP-1 receptor agonists, via rule-based protocols as part of a Titration Plan ordered by a Health Care Provider (HCP). Upon input of required fasting blood glucose data, the device generates an insulin dose according to the prescribed titration plan. Patients record their Fasting Blood Sugar (FBS) daily and the dose presented follows the prescribed protocol. Patient data, either manually entered or entered via connected device, are available for view in the provider portal on the Patient Activity screen. Patients are informed of provider updates or changes to the prescribed titration plan through notifications.The iSage Rx Platform contains all functionality of iSage Rx and Dose Check products. iSage Rx/Dose Check is localized to contain a set of features, configured specifically for a particular geography | include Configurability of features for specific geographies |
{8}------------------------------------------------
{9}------------------------------------------------
{10}------------------------------------------------
{11}------------------------------------------------
| titration algorithms for | based on market | |
|---|---|---|
| their patients. | configurations. The | |
| following are some of the | ||
| After the HCP is | key features that are | |
| registered, an email will | dependent on the | |
| be sent with a link to the | specific national market: | |
| HCP Web-basedApplication and atemporary password.When HCP clicks on thelink, he or she will beprompted to change thetemporary password.Once a new password iscreated, the HCP will beable to login to the HCPWeb-based Applicationwith the new password | Supported medications Supported Clinical TitrationProtocols Supported Wirelessglucometers Supported Languages Supported Hypo-consumables Adult agedefinition | |
| and the username (i.e., | ||
| his or her registered email | ||
| address). | ||
| The HCP Web-basedApplication is used byHCPs to 1) choose fromand customize a patient's | Dose Check is a white-labeled version of iSageRx that is identical toiSage Rx. The twosoftware applications are | |
| basal insulin treatment | identical in function, with | |
| plan, 2) prescribe the | the difference in the user | |
| basal insulin treatment | interface only. iSage Rx | |
| plan, 3) review patient | includes all available | |
| entered data, and 4) | feature configurations, | |
| make adjustments to the | whereas Dose Check | |
| patient's treatment plan.In order to help the HCP | contains only thosefeatures configured for a | |
| create a basal insulin | specific geography. The | |
| treatment plan for a | table in Appendix C. of | |
| patient, the HCP is | this document presents a | |
| presented with a list of | comparison of iSage Rx | |
| clinically validated | and the Dose Check | |
| titration algorithms to | software applications. | |
| select from, along with | ||
| appropriate links to thestudy evidence that | ||
| supports each of thetitrationalgorithms¹. Thispromotes transparencyinto exactly how thetitration algorithm worksfor the HCPs. In addition,the HCP is also presentedwith an option to create acustom titrationalgorithm tailored for hisor her patient. The HCPcan view and adjust allrequired data inputs tothe titration algorithms,including elements suchas:• the starting dose ofbasal insulin (based onthe manufacturer'slabeling);• a patient's fastingBlood Glucose (BG)targets;• a hypoglycemic rangeand insulin doseadjustment• the titration schedule(frequency);• a titration scale andinsulin dose adjustment• the maximum numberof basal units per day(maximum dosage ofbasal insulin) based uponhis/her patient's profile.After a HCP registerspatients in the HCP Web-based Application, thepatient receives an SMSnotification, whichprovides the link todownload the Patient |
{12}------------------------------------------------
{13}------------------------------------------------
| Descriptive | Predicate Device | Proposed Device | Equivalent |
|---|---|---|---|
| Characteristic | |||
| Mobile Application, ordirects them to theappropriate downloadlocation, and anactivation code to beginusing the mobileapplication.The Patient MobileApplication allows apatient to enter BG,present the HCP-selectedtitration schedule for thebasal insulin, and recordthe basal insulin dosetaken. The patient ispresented witheducational messages inthe form of triviaquestions and answers.The patient is alsopresented with coachingmessages upon enteringBG. | |||
| Target Population | Healthcare Provider andAdult diabetic patientsaged 21 and older only | Healthcare Provider andAdult diabetic patients | Same |
| Where Used/UseEnvironment | Home; Single patient-use | Home; Single Patient Use | Same |
| Software Based? | Yes | Yes | Same |
| Dose Calculation | Yes (Basal insulin titrationonly to achieve a desiredtarget BG) | Yes | Same |
| AvailablePlatforms | Web-based; Mobile(iPhone and Android) | Web-based;Mobile (iPhone andAndroid) | Same |
| Rx Only | Yes | Yes | Same |
| Descriptive | Predicate Device | Proposed Device | Equivalent |
| Characteristic | |||
| Contraindications | The iSage Rx deviceshould not be used withpatients who are alsousing bolus insulin and/orpatients who havegestational diabetes. | The followingcontraindications applyto the use of iSage Rx:Use by a person whois not an adult. For replacement ofcommunication withmedical personnel inthe event of anemergency. Use by patients withtype 1 diabetes Use by patients withgestational diabetes. Use by patients usingan insulin pump. | Similar Removal ofcontraindication foruse of iSageRx/Dose Check thatit "Should not beused by patientswith type 2 diabeteswho are also usingprandial insulin"was removed as itwas intended torefer to titration ofprandial insulin.There are nocontraindications toconcurrent use ofprandial insulin. Itwas deemedunnecessary tospecify acontraindication foreach specific type ofinsulin outside ofthose included inthe intended use. |
{14}------------------------------------------------
The intended use for the subject device was re-worded for clarity and to include basal + GLP-1 Receptor Agonists as a supported medication. These modifications do not alter the overall indications for use or risk profile of the iSage Rx Platform.
The description of this functionality in iSage Rx Platform is broadened to include wireless connectivity, consistent with evolving technologies including near field connectivity used in commercially available devices. As new glucose meters are identified by customers who wish to use the iSage Rx Platform, they are evaluated by Amalgam Rx's development team and the technological capability to support desired devices is developed and tested.
Compatible Blood Glucose Meters
The iSage Rx device has the capability to integrate wireless glucose meters to transmit Blood Glucose (BG) data to iSage Rx. Integration with the following devices is supported by the iSage Rx device:
{15}------------------------------------------------
Table 2: Supported Glucose Meters
| Wireless Blood GlucoseMeters (Configurable depending on themarket configuration) | Model Number (mg/dL) |
|---|---|
| CONTOUR® NEXT ONE (Ascensia) | Model 9765 |
| Accu-Chek® Guide (Roche) | Model 923 |
| OneTouch Verio Flex® (LifeScan) | AW 06932401A and AW 06933103A |
| Accu-Chek® Guide Me (Roche) | Model 897 |
| Accu-Chek® Instant(Roche) | Model 972 |
Labelling Information
The following information is provided to the User as IFU's (User Guides) available through the device as well as the "About" section in the product.
Table 3: Labelling Information
| Information | IFU | "About"Screen |
|---|---|---|
| ManufacturerAmalgam Rx, Inc.1007 N. Orange StSuite 400Wilmington, DE 19801United States | Yes | Yes |
| CE symbol with Notified body number (If applicable to thegeography) | Yes | Yes |
| *DistributorAmalgam Rx, Inc.1007 N. Orange StSuite 400Wilmington, DE 19801United States | Yes | Yes |
| *Authorized Representative | Yes | Yes |
| *Brand NameiSage Rx (or) Dose Check | Yes | Yes |
| *Model NumberISR-XX-001 (iSage Rx)DSC-XX-001 (Dose Check) | Yes | Yes |
| Version Number3.x.x.x | No | Yes |
| *Serial Number | No | Yes |
| *Registration Number | No | Yes |
{16}------------------------------------------------
| Information | IFU | "About"Screen |
|---|---|---|
| *Link to User Guide | No | Yes |
| *Customer Support Information | No | Yes |
| *Terms and Conditions | No | Yes |
| *UDI | No | Yes |
| *Intended Use | Yes | Yes |
| Indications for Use | Yes | Yes |
| Supported Operating SystemsSage Rx supports the following operating systems. When a newoperating system update becomes available, compatibility test willbe conducted prior to release.Android: 9.x or lateriOS: 14.x or laterGoogle Chrome: 100.x or laterFirefox: 99.x or laterMicrosoft Edge: 100.x or laterSafari: 15.x or laterIE browser is not supported. | Yes | Yes |
| Device Hardware | Yes | Yes |
| Cybersecurity Information | Yes | Yes |
| Availability of IFU | Yes | Yes |
| DisclaimersPlease be aware that, although iSage Rx contains messagingfunctionality to support patients who report hypoglycemic andhyperglycemic blood glucose measurements, iSage Rx (including thewebsite, the mobile app, and services) is not to be used foremergencies and we disclaim all liability for the use of iSage Rx inconnection with emergencies. If you are a patient user, please go toyour nearest hospital in the event of an emergency. If you are aprovider, do not use iSage Rx to communicate with your patientsabout emergency medical issues | Yes | Yes |
VII. PERFORMANCE DATA
Functional Testing
All product development activities for the iSage Rx Platform were conducted in compliance with EN ISO 13458:2016 under the quality management system that has been certified by Intertek Medical Notified Body AB (Certificate Number:0139273). Due to the nature of the iSage Rx Platform as standalone software, documentation is not applicable related to biocompatibility, electrical safety and electromagnetic compatibility, mechanical and acoustic testing, biological safety, sterilization, shelf-life, and medicinal substances, tissues, or materials of animal original, blood or tissues or derivatives of human origin.
{17}------------------------------------------------
The following performance data were provided in support of the substantial equivalence determination.
Software Verification and Validation Testing
Software verification and validation testing were conducted, and documentation was provided as recommended by FDA's Guidance for Industry and FDA Staff, "Content of Premarket Submissions for Device Software Functions." The Documentation Level was determined as "Basic" based on the risks of the iSage Rx software function(s) in the context of the device's intended use. The following is the rationale as to why Basic Documentation was selected instead of Enhanced Documentation for this premarket submission.
Rationale: A failure or latent flaw in the software will not result in serious injury or death to the patient or operator. The user of the Application could be exposed to harms due to malfunction of the device, user error, or unclear device labeling. The overall probability of occurrence of harms is generally low after implementation of risk control measures – the probability of occurrence for all harms that are on the serious or higher severity level all are all on the remote or lower level.
Software verification and validation testing of design control mitigations implemented for identified risks to demonstrate the effectiveness of the mitigations for the intended purpose, when used by intended users in accordance with the intended use environments. Verification and validation of the key design requirements associated with safety and performance are summarized in nonclinical datasets in the form of testing protocols and reports.
The Traceability Matrix for iSage Rx Platform (AML-PDV-ISP-100-MTX-001) displays a matrix of all requirements by type and ID along with the related individual verification and validation test cases demonstrating that the requirement has been satisfied. Tabs within the Traceability Matrix for iSage Rx Platform delineate requirements that are role specific as well as functional or non-functional.
Summary
Having no significant differences from the predicate device, it is therefore concluded that the iSage Platform has a similar safety and effectiveness profile and is substantially equivalent.
Conclusion:
iSage Rx Platform shows no significant differences from the predicate device, which is proprietary to Amalgam Rx. Hence the iSage Rx platform, including its white-label version Dose Check, is substantially equivalent to the predicate device. The non-clinical data affirms the device's safety, and the software verification and validation tests confirm that the iSage Rx Platform will perform as intended under specified use conditions. Therefore, it is concluded that there is no significant difference in the basic functionality, safety, and effectiveness between the iSage Rx Platform and the predicate device.
§ 868.1890 Predictive pulmonary-function value calculator.
(a)
Identification. A predictive pulmonary-function value calculator is a device used to calculate normal pulmonary-function values based on empirical equations.(b)
Classification. Class II (performance standards).