The Advisor Pro Platform is intended for the management of diabetes by people with diabetes and their health care providers in order to report, log, track, share, monitor and review their data using the dedicated computer or mobile software. Advisor Pro Platform also enables communication between people with diabetes and their health care providers as well as among health care providers.

The Advisor Pro Platform enables the healthcare provider to use the Advisor Pro Algorithms for treatment recommendations as described below and prescribe the Advisor Pro Bolus Calculator for patient use.

Advisor Pro Algorithm is a decision-support software intended for assisting healthcare professionals in the management of their patients with diabetes who monitor their glucose levels using continuous glucose monitor (CGM) and/or Self-Monitoring Blood Glucose (SMBG) meter; and use any of the following insulin types as their therapy to manage glucose levels via subcutaneous injections or continuous sub-cutaneous insulin infusion (CSII; insulin pump) reported either manually or automatically:

Long Acting insulins (for injections only)
Short acting insulins:
- Rapid acting analogs (for injections and insulin pump according to manufacturer indications for use)
- Regular human insulin (for injections only)

The Advisor Pro algorithm is intended to be used for patients with:

Type 1 diabetes over the age of 6 using an insulin pump or subcutaneous insulin injections.
Type 2 diabetes over the age of 10 who use subcutaneous insulin injections.

Advisor Pro Algorithm is indicated for use by healthcare professionals when analyzing CGM, SMBG and/or insulin delivery data to generate recommendations for optimizing a patient's insulin treatment plan for basal therapy and/or bolus therapy and/or glucose targets; without considering the full clinical status of a particular patient. Advisor Pro Algorithm does not replace clinical judgment.

The Advisor Pro Bolus Calculator, a component of the DreaMed Diary App, is a diabetes management tool for people with type 1 diabetes above the age of 6 and type 2 diabetes above the age of 10, who use subcutaneous insulin injections therapy (not for pump use). This tool can help calculate their rapid acting analogs for insulin bolus doses based on user-entered blood glucose and/or meal information.

The initial setup of the user's treatment plans, and bolus calculator settings must be performed by a healthcare provider.

Device Description

The Advisor Pro Platform is a software device that is designed to be a diabetes management platform. It includes the Advisor Pro Algorithm that provides insulin therapy adjustment recommendations to physicians to assist in the management of diabetes for patients with Type 1 diabetes using an insulin pump or multiple daily injections, a continuous glucose monitoring (CGM) system and/or self-management blood glucose meter (SMBG). The Advisor Pro Algorithm also provides insulin therapy adjustment recommendations to physicians to assist in the management of diabetes for patients with Type 2 diabetes on basal-bolus therapy via multiple daily injections (MDI), a continuous glucose monitoring (CGM) system and/or self-management blood glucose meter (SMBG).

The Advisor Pro Algorithm gathers and analyzes information inputted through the Diabetes Management Systems (DMS), which collects biological input information from various diabetes devices and data sources including the DreaMed Diary App. Diabetes device information required and used by Advisor Pro Algorithm includes glucose readings (either CGM sensor readings and/or capillary blood glucose measurements), insulin dosing logs, and meal data during daily routine care.

Following data collection and analysis, the Advisor Pro Algorithm generates results containing summary data and recommendations for adjustments to the patient's insulin therapy parameters, including basal insulin delivery rate(s), insulin to carbohydrate ratio and correction factor (insulin sensitivity) for pump patients and for MDI patients a daily injection plan including a basal plan and either a sliding scale or insulin to carbohydrate ratio and correction factor (insulin sensitivity) for bolus injections. Advisor Pro Algorithm may also advise on personalized diabetes management tips. Results are sent to the Diabetes Management System, which displays results to physicians and a report provided by the algorithm. The physician can approve, reject or change the recommendations and issue the updated treatment plan to the patient.

For MDI patients using rapid acting analogs for insulin bolus dose, the healthcare provider may prescribe the Advisor Pro Bolus Calculator which is integrated in the DreaMed Diary App to aid in calculating their bolus injections.

AI/ML Overview

The provided text describes the DreaMed Advisor Pro Platform, a software device intended for diabetes management. It includes two main components: the Advisor Pro Algorithm (a decision-support tool for healthcare professionals) and the Advisor Pro Bolus Calculator (for patient use).

Here's an analysis of the acceptance criteria and the study proving device performance based on the provided text:

1. Table of Acceptance Criteria and Reported Device Performance

The document does not explicitly present a table of quantitative acceptance criteria with corresponding performance metrics like sensitivity, specificity, accuracy, or specific thresholds for agreement. Instead, it focuses on demonstrating that the device's recommendations are "as good as" or "similar to" those of experts.

Acceptance Criteria (Implied)	Reported Device Performance
Device performs according to stated intended use ("functional testing")	"All test results fell within the pre-determined specification parameters and acceptance criteria."
User interface adequately validated for use	"The human factors, design, and labeling information provided in the submission confirm that the user interface has been adequately validated for use per the labeling." (Human factors testing was conducted with intended user populations of patients and healthcare providers)
Algorithm recommendations agree with expert recommendations	"The study results show that the recommendations of the Advisor Pro Algorithm Pro for MDI patients Type 1 and Type 2 were significantly as good as the recommendations of expert in the basal and bolus plan with regards to the overall level of agreement in the direction of change. Therefore, the Advisor Pro Algorithm recommendations could be considered similar to those given by healthcare professional who work at leading centers with a wealth of experience in the field of diabetes and who are especially familiar with diabetes technology devices."
No new safety or effectiveness concerns	"DreaMed Diabetes believes that the changes as described in this 510(k) submission do not present additional safety or effectiveness concerns for the Advisor Pro Platform including the Advisor Pro Algorithm as well as the Advisor Pro Bolus Calculator and is substantially equivalent to the predicates cited."

2. Sample Size Used for the Test Set and Data Provenance

Test Set Sample Size: The clinical study involved a data set of 17 Type 1 patients and 15 Type 2 patients.
Data Provenance: The document does not specify the country of origin for the data. It indicates the study was "retrospective clinical study."

3. Number of Experts Used to Establish the Ground Truth for the Test Set and Their Qualifications

Number of Experts: A total of 36 experts were involved.
Qualifications of Experts: The text states these were "healthcare professional who work at leading centers with a wealth of experience in the field of diabetes and who are especially familiar with diabetes technology devices." Specific professional titles (e.g., endocrinologist, specialized diabetes nurse), years of experience, or board certifications are not provided.

4. Adjudication Method for the Test Set

The document states, "Recommendations were compared to examine the level of agreement between one expert to his colleague versus the level of agreement between Advisor Pro Algorithm recommendations and experts." This implies some form of comparison or consensus evaluation, but a specific adjudication method (e.g., 2+1, 3+1) is not explicitly detailed. It seems to be a comparison of agreement levels rather than a formal adjudication process to establish a single ground truth from multiple expert reads for each case.

5. If a Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study Was Done, and Effect Size

While the study involved multiple experts evaluating cases and comparing their recommendations to the algorithm and to each other, the description doesn't explicitly label it as a formal MRMC comparative effectiveness study in the sense of directly measuring human reader improvement with AI assistance vs. without.

The study aimed to show that the AI's recommendations were "as good as" expert recommendations. It compared "the level of agreement between one expert to his colleague versus the level of agreement between Advisor Pro Algorithm recommendations and experts."

Therefore, it was not a direct MRMC study to quantify how much human readers improve with AI assistance. It was designed to show the equivalence/similarity of the algorithm's recommendations to those of experts. No effect size for human reader improvement with AI assistance is reported because that was not the stated purpose of this particular comparison.

6. If a Standalone (Algorithm Only Without Human-in-the-Loop Performance) Was Done

Yes, the study described is a standalone performance evaluation of the Advisor Pro Algorithm's recommendations compared to expert recommendations. The algorithm generated recommendations independently, which were then compared to expert decisions.

7. The Type of Ground Truth Used

The ground truth for the clinical study appears to be expert consensus or expert recommendations for insulin therapy adjustments. The algorithm's recommendations were compared against the recommendations of these experts to establish "level of agreement."

8. The Sample Size for the Training Set

The document does not provide information regarding the sample size used for the training set for the Advisor Pro Algorithm. The clinical study described involved a test set.

9. How the Ground Truth for the Training Set Was Established

The document does not provide information on how the ground truth for the training set was established. The clinical study described focuses on the evaluation of the algorithm's performance on a test set, not on its training data.

Summary

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September 28, 2021

DreaMed Diabetes Ltd. Inbal Beinglass Peled 5 Mota Gur St. Petah Tikva, 4952701 Israel

Re: K210561

Trade/Device Name: Advisor Pro Platform Regulation Number: 21 CFR 862.1358 Regulation Name: Insulin Therapy Adjustment Device Regulatory Class: Class II Product Code: QCC, NDC Dated: February 22, 2021 Received: February 25, 2021

Dear Inbal Beinglass Peled:

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 (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 located 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.

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

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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 803) for devices or postmarketing safety reporting (21 CFR 4, Subpart B) for combination products (see https://www.fda.gov/combination-products/guidance-regulatory-information/postmarketing-safety-reportingcombination-products); good manufacturing practice requirements as set forth in the quality systems (OS) regulation (21 CFR Part 820) for devices or current good manufacturing practices (21 CFR 4, Subpart A) for combination products; and, if applicable, the electronic product radiation control provisions (Sections 531-542 of the Act); 21 CFR 1000-1050.

Also, please note the regulation entitled, "Misbranding by reference to premarket notification" (21 CFR Part 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,

Kellie B. Kelm -S

Kellie B. Kelm, Ph.D. Director Division of Chemistry and Toxicology Devices OHT7: Office of In Vitro Diagnostics and Radiological Health Office of Product Evaluation and Quality Center for Devices and Radiological Health

Enclosure

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Indications for Use

510(k) Number (if known) K210561

Device Name Advisor Pro Platform

Indications for Use (Describe)

Advisor Pro Platform

The Advisor Pro Platform is intended for the management of diabetes and their health care providers in order to report, log, track, share, monitor and review their data using the dedicated computer or mobile software. Advisor Pro Platform also enables communication between people with diabetes and their health care providers as well as among health care providers.

Advisor Pro Algorithm

Long Acting insulins (for injections only) 0
Short acting insulins: 0
- Rapid acting analogs (for injections and insulin pump according to manufacturer indications for use)
- . Regular human insulin (for injections only)

The Advisor Pro algorithm is intended to be used for patients with:

Type 1 diabetes over the age of 6 using an insulin pump or subcutaneous insulin injections.
. Type 2 diabetes over the age of 10 who use subcutaneous insulin injections.

Advisor Pro Algorithm is indicated for use by healthcare professionals when analyzing CGM, SMBG and/or insulin delivery data to generate recommendations for optimizing a patient's insulin treatment plan for bolus therapy and/or glucose targets; without considering the full clinical status of a particular patient. Advisor Pro Algorithm does not replace clinical judgment.

Advisor Pro Bolus Calculator

The initial setup of the user's treatment plans, and bolus calculator settings must be performed by a healthcare provider.

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.

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Image /page/4/Picture/0 description: The image shows the logo for Dreamed Diabetes AI. The word "dreamed" is written in a light blue color, while the word "diabetes ai" is written in a smaller font size and is located below the word "dreamed". The "med" portion of the word "dreamed" is written in gray.

510(k) SUMMARY DreaMed Advisor Pro Platform

Submitter's Name, Address, Telephone Number, Contact Person and Date Prepared

DreaMed Diabetes Ltd. 5 Mota Gur St. Petah Tikva 4952701 lsrael

Contact Person: Inbal Beinglass Peled Email: inbal.peled@dreamed.ai Phone: +972-52-3642760 Date Prepared:February 22, 2021

Name of Device and Name/Address of Sponsor

Advisor Pro Platform DreaMed Diabetes Ltd. 5 Mota Gur Street Petah Tikva 4952701 Israel

Common or Usual Name

Insulin Therapy Adjustment Device

Classification

Class II, 21 CFR 862.1358, Product Code: QCC

Predicate Devices

DreaMed Advisor Pro, K201476

Reference Device: Accu-Chek Connect Diabetes Management App, Roche Diabetes Care Inc., K150910

Intended Use / Indications for Use

Advisor Pro Platform

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Image /page/5/Picture/0 description: The image shows the logo for Dreamed Diabetes AI. The word "dreamed" is written in a light blue color, while the word "diabetes ai" is written in a smaller font size and is located below the word "dreamed". The word "diabetes ai" is also written in a light blue color.

Advisor Pro Algorithm

o Long acting insulins (for injections only)
Short acting insulins: o
- · Rapid acting analogs (for iniections and insulin pump according to manufacturer indications for use)
  - · Reqular human insulin (for iniections only)

The Advisor Pro algorithm is intended to be used for patients with:

. Type 1 diabetes over the age of 6 using an insulin pump or subcutaneous insulin injections.
. Type 2 diabetes over the age of 10 who use subcutaneous insulin injections.

Advisor Pro Algorithm is indicated for use by healthcare professionals when analyzing CGM. SMBG and/or insulin delivery data to generate recommendations for optimizing a patient's insulin treatment plan for basal therapy and/or bolus therapy and/or glucose tarqets; without considering the full clinical status of a particular patient. Advisor Pro Algorithm does not replace clinical judgment.

Advisor Pro Bolus Calculator

The initial setup of the user's treatment plans, and bolus calculator settings must be performed by a healthcare provider.

Device Description

The Advisor Pro Algorithm gathers and analyzes information inputted through the Diabetes Manaqement Systems (DMS), which collects biological input information from various diabetes devices and data sources including the DreaMed Diary App. Diabetes device information

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Image /page/6/Picture/0 description: The image shows the logo for Dreamed Diabetes AI. The word "dreamed" is written in a sans-serif font, with the "drea" in a light blue color and the "med" in a dark gray color. Below the word "dreamed" is the phrase "diabetes ai" in a smaller, light blue sans-serif font. The logo is simple and modern, and the colors are calming and professional.

required and used by Advisor Pro Algorithm includes glucose readings (either CGM sensor readings and/or capillary blood glucose measurements), insulin dosing logs, and meal data during daily routine care.

Following data collection and analysis, the Advisor Pro Algorithm generates results containing summary data and recommendations for adjustments to the patient's insulin therapy parameters, including basal insulin delivery rate(s), insulin to carbohydrate ratio and correction factor (insulin sensitivity) for pump patients and for MDI patients a daily iniection plan including a basal plan and either a sliding scale or insulin to carbohydrate ratio and correction factor (insulin sensitivity) for bolus injections. Advisor Pro Algorithm may also advise on personalized diabetes manaqement tips. Results are sent to the Diabetes Management System, which displays results to physicians and a report provided by the algorithm. The physician can approve, reject or change the recommendations and issue the updated treatment plan to the patient.

Substantial Equivalence

The Advisor Pro Platform is as safe and effective as the predicate devices. The Advisor Pro Platform has the same principles of operation as the predicate devices.

With respect to the technological characteristics, the difference in the specification for minimal BG required, the difference does not affect the safety and effectiveness of the device as the recommendations before and after the change ultimately remain the same and thus the devices are substantially equivalent.

With respect to the indication for use we conclude that the differences in the indication for use between the predicates in allowing HCPs to receive insulin therapy adjustment recommendations for their Type 1 and Type 2 MDI patients do not affect safety and effectiveness of the device. This is based on the risk analysis, the clinical evidence and the human factors testing which show that the device is safe and effective for this additional treatment population. The indications for use differences between the Advisor Pro Algorithm and its predicate devices raise no new issues of safety or effectiveness. Thus, the Advisor Pro Alqorithm is substantially equivalent to its predicate device.

The Advisor Pro Bolus Calculator is substantially equivalent to the predicate device as it is has the same intended use and any minor differences related to technological characteristics such as: max bolus size and meal size type do not raise any new question of safety and effectiveness.

Software

Advisor Pro Platform was validated pursuant to the Major Level of Concern requirements.

Design validation testing results confirmed that the Advisor Pro Platform performs according to the stated intended use. Software evaluation consisted of functional testing performed pursuant to DreaMed's software test plan. All test results fell within the pre-determined specification parameters and acceptance criteria.

Special controls were implemented and validated according to DreaMed software test plan.

Human Factors

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Image /page/7/Picture/0 description: The image shows the logo for Dreamed Diabetes AI. The word "dreamed" is written in a sans-serif font, with the "drea" in a light blue color and the "med" in a dark gray color. Below the word "dreamed" is the phrase "diabetes ai" in a smaller, light blue sans-serif font.

Human factors testing was conducted with the intended user populations of patients and healthcare providers. The Human Factors validation was documented according to FDA Guidance - Applying Human Factors and Usability Engineering to Medical Devices (February 3, 2016). The human factors, design, and labeling information provided in the submission confirm that the user interface has been adequately validated for use per the labeling.

Clinical Evidence

Additional retrospective clinical study was performed to evaluate physicians' strategies of adjustment of Type 1 and Type 2 MDI patients' basal-bolus therapy plan based on glucose and insulin injection data and to compare results to automated recommendations given by the Advisor Pro Algorithm. The study involved a data set of 17 Type 1 patients and 15 Type 2 patients and a total of 36 experts.

Recommendations were compared to examine the level of agreement between one expert to his colleaque versus the level of agreement between Advisor Pro Algorithm recommendations and experts. The study results show that the recommendations of the Advisor Pro Algorithm Pro for MDI patients Type 1 and Type 2 were significantly as good as the recommendations of expert in the basal and bolus plan with regards to the overall level of agreement in the direction of change. Therefore, the Advisor Pro Algorithm recommendations could be considered similar to those given by healthcare professional who work at leading centers with a wealth of experience in the field of diabetes and who are especially familiar with diabetes technology devices.

Conclusions

DreaMed Diabetes believes that the changes as described in this 510(k) submission do not present additional safety or effectiveness concerns for the Advisor Pro Platform including the Advisor Pro Algorithm as well as the Advisor Pro Bolus Calculator and is substantially equivalent to the predicates cited.

Regulation Number and Section

§ 862.1358 Insulin therapy adjustment device.

(a)
Identification. An insulin therapy adjustment device is a device intended to incorporate biological inputs, including glucose measurement data from a continuous glucose monitor, to recommend insulin therapy adjustments as an aid in optimizing insulin therapy regimens for patients with diabetes mellitus.(b)
Classification. Class II (special controls). The special controls for this device are:(1) Design verification and validation must include the following:
(i) A complete description of the required data inputs, including timeframe over which data inputs must be collected and number of data points required for accurate recommendations;
(ii) A complete description of the types of device outputs and insulin therapy adjustment recommendations, including how the recommendations are generated;
(iii) Robust data demonstrating the clinical validity of the device outputs and insulin therapy recommendations;
(iv) A robust assessment of all input data specifications, including accuracy requirements for continuous glucose monitors and other devices generating data inputs, to ensure accurate and reliable therapy adjustment recommendations. This assessment must include adequate clinical justification for each specification;
(v) A detailed strategy to ensure secure and reliable means of data transmission to and from the device, including data integrity checks, accuracy checks, reliability checks, and security measures;
(vi) Robust data demonstrating that users can understand and appropriately interpret recommendations generated by the device; and
(vii) An appropriate mitigation strategy to minimize the occurrence of dosing recommendation errors, and to mitigate the risk to patients of any residual dosing recommendation errors to a clinically acceptable level.
(2) The device must not be intended for use in implementing automated insulin dosing.
(3) Your 21 CFR 809.10(b) labeling must include:
(i) The identification of specific insulin formulations that have been demonstrated to be compatible with use of the device;
(ii) A detailed description of the specifications of compatible devices that provide acceptable input data (e.g., continuous glucose monitors, insulin pumps) used to provide accurate and reliable therapy adjustment recommendations;
(iii) A detailed description of all types of required data (inputs) and dosing recommendations (outputs) that are provided by the device; and
(iv) A description of device limitations, and instructions to prevent possible disruption of accurate therapy adjustment recommendations (e.g., time zone changes due to travel).