Predicate Devices

Reference Devices

AI/ML (Artificial Intelligence / Machine Learning)

No
The device description explicitly states that the titration is performed "via rule-based protocols," which is characteristic of traditional programming rather than AI/ML. There are no mentions of AI, ML, or related concepts like training or test sets.

Therapeutic

Yes
The device is described as "a prescription-use only (Rx-only) software device" that helps patients "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," indicating its therapeutic purpose in managing type 2 diabetes.

Diagnostic

No

The device is designed to manage and titrate medication based on existing diagnoses and blood glucose levels, not to diagnose a new condition. Its purpose is to help patients and healthcare providers understand and follow a titration plan and reach optimal medication doses.

SaMD (Software as a Medical Device)

Yes

The device description explicitly states that the iSage Rx patient app is a "stand-alone, prescription-use only (Rx-only) software device". While it is part of a larger system that includes web-based components, the core patient-facing device is described as software. The performance studies also focus on "Software Verification and Validation Testing".

IVD (In Vitro Diagnostic)

Based on the provided information, this device is not an IVD (In Vitro Diagnostic).

Here's why:

IVD Definition: In vitro diagnostics are tests performed on samples taken from the human body, such as blood, urine, or tissue, to detect diseases, conditions, or infections. They are used to provide information for diagnosis, monitoring, or screening.
iSage Rx Function: The description of iSage Rx clearly states its purpose is to help patients and healthcare providers manage basal insulin titration based on blood glucose levels. It provides a software-based system for understanding and following a titration plan.
Lack of Sample Analysis: There is no mention of iSage Rx analyzing any biological samples from the patient. It takes blood glucose readings (which are obtained through a separate device, likely a glucose meter) as input and provides guidance on insulin dosage.
Focus on Treatment Management: The primary function is to support the management of a treatment plan (insulin titration), not to diagnose or monitor a condition through the analysis of biological samples.

Therefore, iSage Rx falls under the category of a software device used for treatment management and support, not an in vitro diagnostic device.

PCCP (Predetermined Change Control Plan) Authorized

N/A

Overview

Intended Use / 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

Product codes

NDC

Device Description

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.

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:

1. Name of supported medication patient has been prescribed.
1. Starting dose of the supported medication
1. Target fasting blood glucose range.
1. Number of units to increase or decrease the supported medication based on an average fasting blood glucose values.
1. The frequency of the titration (1-7 days)
1. 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.
1. 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 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.

Mentions image processing

Not Found

Mentions AI, DNN, or ML

Not Found

Input Imaging Modality

Not Found

Anatomical Site

Not Found

Indicated Patient Age Range

adult patients

Intended User / Care Setting

adult patients with type 2 diabetes, and by their healthcare providers (HCP); nonacute care setting

Description of the training set, sample size, data source, and annotation protocol

Not Found

Description of the test set, sample size, data source, and annotation protocol

Not Found

Summary of Performance Studies (study type, sample size, AUC, MRMC, standalone performance, key results)

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.

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.

Key Results: 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.
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.

Key Metrics (Sensitivity, Specificity, PPV, NPV, etc.)

Not Found

Predicate Device(s)

K161865

Reference Device(s)

No reference devices were used in this submission

Predetermined Change Control Plan (PCCP) - All Relevant Information

Not Found

Regulation Number and Section

§ 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).

Summary

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)

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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 Insulin
Titration)	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:

1. Name of supported medication patient has been prescribed.
1. Starting dose of the supported medication
1. Target fasting blood glucose range.
1. Number of units to increase or decrease the supported medication based on an average fasting blood glucose values.
1. The frequency of the titration (1-7 days)
1. 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.
1. 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.

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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:

| Descriptive

Characteristic	Predicate Device	Proposed Device	Equivalent
Trade Name	iSage Rx (iSage Rx Basal
Insulin Titration)	iSage Rx Platform (iSage
Rx Basal Insulin Titration)	Same
510(k) Number	K161865	510(k) under review	NA
Classification
Product Code	NDC	NDC	Same
Device
Classification
Name	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 for
Use	iSage Rx (iSage Rx Basal
Insulin Titration) is
software indicated for use
by adult patients aged 21
and above who have type
2 diabetes and their
healthcare providers to
titrate basal insulin. 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 2 diabetes who are
also using prandial insulin
or patients with type 1
diabetes, gestational
diabetes, or patients
using an insulin pump.	iSage Rx Platform
software is 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
insulinsTitration of
combinations of
basal insulin and
GLP-1 receptor
agonists	Similar —Differences
include:
Added "Support for
the Titration of
combinations of
basal insulin and
GLP-1 receptor
agonists" as a new
intended use.
Intended Use	iSage Rx (iSage Rx Basal	iSage Rx Platform	Similar –Differences
	Insulin Titration) is
software indicated for use
by adult patients aged 21
and above who have type
2 diabetes and their
healthcare providers to
titrate basal insulin. 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 2 diabetes who are
also using prandial insulin
or patients with type 1
diabetes, gestational
diabetes, or patients
using an insulin pump.	software is 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 Patients using iSage Rx
can record their blood
glucose levels, view their
Healthcare Provider's
dosing plan for supported
medications, and record
the medication dose
taken.

iSage Rx connects with
the following devices:
Glucose meters
to transmit Blood
Glucose (BG)
data | include:
Added "Support for
the Titration of
combinations of
basal insulin and
GLP-1 receptor
agonists" as a new
intended use. Removed
contraindication for
prandial insulin.
Removal of
contraindication for
use of iSage
Rx/Dose Check that
it "Should not be
used by patients
with type 2 diabetes
who are also using
prandial insulin"
was removed as it
was intended to
refer to titration of
prandial insulin.
There are no
contraindications to
concurrent use of
prandial insulin. It
was deemed
unnecessary to
specify a
contraindication for
each specific type of
insulin outside of
those included in
the intended use. |
| Descriptive
Characteristic | 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 |

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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-based
Application and a
temporary password.
When HCP clicks on the
link, he or she will be
prompted to change the
temporary password.
Once a new password is
created, the HCP will be
able to login to the HCP
Web-based Application
with the new password	Supported medications Supported Clinical Titration
Protocols Supported Wireless
glucometers Supported Languages Supported Hypo-
consumables Adult age
definition
and the username (i.e.,
his or her registered email
address).
The HCP Web-based
Application is used by
HCPs to 1) choose from
and customize a patient's	Dose Check is a white-
labeled version of iSage
Rx that is identical to
iSage Rx. The two
software 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 those
features 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 the
study evidence that

supports each of the
titration
algorithms¹. This
promotes transparency
into exactly how the
titration algorithm works
for the HCPs. In addition,
the HCP is also presented
with an option to create a
custom titration
algorithm tailored for his
or her patient. The HCP
can view and adjust all
required data inputs to
the titration algorithms,
including elements such
as:
• the starting dose of
basal insulin (based on
the manufacturer's
labeling);
• a patient's fasting
Blood Glucose (BG)
targets;
• a hypoglycemic range
and insulin dose
adjustment
• the titration schedule
(frequency);
• a titration scale and
insulin dose adjustment
• the maximum number
of basal units per day
(maximum dosage of
basal insulin) based upon
his/her patient's profile.

After a HCP registers
patients in the HCP Web-
based Application, the
patient receives an SMS
notification, which
provides the link to
download the Patient | | |

12

13

Descriptive	Predicate Device	Proposed Device	Equivalent
Characteristic
	Mobile Application, or
directs them to the
appropriate download
location, and an
activation code to begin
using the mobile
application.

The Patient Mobile
Application allows a
patient to enter BG,
present the HCP-selected
titration schedule for the
basal insulin, and record
the basal insulin dose
taken. The patient is
presented with
educational messages in
the form of trivia
questions and answers.
The patient is also
presented with coaching
messages upon entering
BG. | | |
| Target Population | Healthcare Provider and
Adult diabetic patients
aged 21 and older only | Healthcare Provider and
Adult diabetic patients | Same |
| Where Used/Use
Environment | Home; Single patient-use | Home; Single Patient Use | Same |
| Software Based? | Yes | Yes | Same |
| Dose Calculation | Yes (Basal insulin titration
only to achieve a desired
target BG) | Yes | Same |
| Available
Platforms | Web-based; Mobile
(iPhone and Android) | Web-based;
Mobile (iPhone and
Android) | Same |
| Rx Only | Yes | Yes | Same |
| Descriptive | Predicate Device | Proposed Device | Equivalent |
| Characteristic | | | |
| Contraindications | The iSage Rx device
should not be used with
patients who are also
using bolus insulin and/or
patients who have
gestational diabetes. | The following
contraindications apply
to the use of iSage Rx:
Use by a person who
is not an adult. For replacement of
communication with
medical personnel in
the event of an
emergency. Use by patients with
type 1 diabetes Use by patients with
gestational diabetes. Use by patients using
an insulin pump. | Similar Removal of
contraindication for
use of iSage
Rx/Dose Check that
it "Should not be
used by patients
with type 2 diabetes
who are also using
prandial insulin"
was removed as it
was intended to
refer to titration of
prandial insulin.
There are no
contraindications to
concurrent use of
prandial insulin. It
was deemed
unnecessary to
specify a
contraindication for
each specific type of
insulin outside of
those included in
the 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 Glucose
Meters (Configurable depending on the

market 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 |
|-------------------------------------------------------------------------------------------------------------|-----|-------------------|
| Manufacturer
Amalgam Rx, Inc.
1007 N. Orange St
Suite 400
Wilmington, DE 19801
United States | Yes | Yes |
| CE symbol with Notified body number (If applicable to the
geography) | Yes | Yes |
| *Distributor
Amalgam Rx, Inc.
1007 N. Orange St
Suite 400
Wilmington, DE 19801
United States | Yes | Yes |
| *Authorized Representative | Yes | Yes |
| *Brand Name
iSage Rx (or) Dose Check | Yes | Yes |
| *Model Number
ISR-XX-001 (iSage Rx)
DSC-XX-001 (Dose Check) | Yes | Yes |
| Version Number
3.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 Systems
Sage Rx supports the following operating systems. When a new
operating system update becomes available, compatibility test will
be conducted prior to release.
Android: 9.x or later
iOS: 14.x or later
Google Chrome: 100.x or later
Firefox: 99.x or later
Microsoft Edge: 100.x or later
Safari: 15.x or later
IE browser is not supported. | Yes | Yes |
| Device Hardware | Yes | Yes |
| Cybersecurity Information | Yes | Yes |
| Availability of IFU | Yes | Yes |
| Disclaimers
Please be aware that, although iSage Rx contains messaging
functionality to support patients who report hypoglycemic and
hyperglycemic blood glucose measurements, iSage Rx (including the
website, the mobile app, and services) is not to be used for
emergencies and we disclaim all liability for the use of iSage Rx in
connection with emergencies. If you are a patient user, please go to
your nearest hospital in the event of an emergency. If you are a
provider, do not use iSage Rx to communicate with your patients
about 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.