The InPen is a home-use reusable pen injector for single-patient use by people with diabetes age 12 and older for the self-injection of a desired dose of insulin. The pen injector is compatible with Lilly Humalog® U-100 3.0 mL cartridges of insulin and single-use detachable and disposable pen needles (not included). The pen injector allows the user to dial the desired dose from 0.5 to 30 units in one-half (1/2) unit increments.

The InPen is a home-use reusable pen injector for single-patient use by people with diabetes age 12 and older for the self-injection of a desired dose of insulin. The pen injector is compatible with Novo Nordisk Novolog® U-100 3.0 mL cartridges of insulin and single-use detachable and disposable pen needles (not included). The pen injector allows the user to dial the desired dose from 0.5 to 30 units in one-half (1/2) unit increments.

The InPen dose calculator, a component of the InPen app, is indicated for the management of diabetes by people with diabetes age 12 and older by calculating an insulin dose or carbohydrate intake based on user entered data. Prior to use, a healthcare professional must provide the patient-specific target blood glucose, insulin-to-carbohydrate ratio, and insulin sensitivity parameters to be programmed into the software.

Device Description

The InPen System consists of a manually-controlled pen injector and an app containing a logbook and a dose (bolus) calculator.

The InPen is a manual pen injector containing a non-replaceable battery and electronics to communicate via Bluetooth® with the app on an iOS® mobile device. The intended dose is manually set by the user by rotating a dose knob. The insulin is injected by manually depressing the dose knob which causes the piston in the insulin cartridge to expel the intended dose. The InPen is provided in two different models for compatibility with the available U-100 insulin cartridges, i.e. Humalog® and Novolog®. The device is provided with Instructions For Use and a Quick Start Guide. The device is used with sterile needles and U-100 insulin cartridges (supplied separately).

The app is designed to manage the wireless transfer of insulin dose data from the InPen, log insulin dose data, and provide a dose calculator to aid mealtime insulin dose calculations. The insulin dose calculations provided by the app are meant for patients undergoing multiple daily injection (MDI) therapy. The InPen app is not intended to serve as an accessory to an insulin pump.

AI/ML Overview

Here's an analysis of the acceptance criteria and supporting study for the InPen System, based on the provided document:

1. Table of Acceptance Criteria and Reported Device Performance

The document doesn't explicitly present a direct table of "acceptance criteria" alongside "reported device performance" for each specific requirement in the way a formal test report might. However, it states that the device was tested against specific standards and "met the acceptance criteria." I will synthesize this information from the "Performance Data" section.

Acceptance Criterion (Standard or Requirement)	Reported Device Performance
Biocompatibility:
ISO 10993-1 (Cytotoxicity, Sensitization, Irritation/Intracutaneous Reactivity)	InPen System is considered biocompatible and acceptable for use.
Electromagnetic Compatibility & Electrical Safety:
IEC 60601-1 (Basic Safety & Essential Performance)	Complies with requirements.
IEC 60601-1-2 (EMC)	Complies with requirements.
IEC 60601-1-11 (Home Healthcare Environment)	Complies with requirements.
Software:
FDA Guidance for Industry and FDA Staff, "Guidance for the Content of Premarket Submissions for Software Contained in Medical Devices" (Software Level of Concern: Major)	Software verification and validation testing conducted, documentation provided.
Bench Testing (Pen Injector):
ISO 11608-1 (Needle-Based Injection Systems)	InPen System functioned as intended and met the acceptance criteria in all instances (general design, mechanical characterization, dose accuracy).
ISO 11608-4 (Pen-Injectors For Medical Use)	Requirements met where appropriate due to modifications for electronic/electromechanical pen-injectors.
Clinical Evidence (User Interface/Human Factors):
Hazard analysis according to ISO 14971	Hazard analysis completed.
Human Factors Summative Study (absence of critical errors leading to hazard)	After self-training, patients were able to use the InPen System without making critical errors that could lead to a hazard. No new use-related hazards identified.
Dose Calculator Functionality:
Standard approach using HCP-specified insulin-to-carbohydrate ratio and insulin sensitivity factors.	Uses standard approach.
Consideration for insulin on-board based on specific published study.	Includes consideration for insulin on-board based on Mudaliar, et al. (1999) study.

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

Test Set Sample Size: The document mentions a "comprehensive Human Factors Summative Study" involving "patients with sufficient diabetes knowledge." However, it does not specify the exact sample size for this study.
Data Provenance: The document does not explicitly state the country of origin for the data used in the Human Factors Summative Study. It is implied to be a prospective study as it involved patients completing tasks with the InPen System.

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

The document does not provide information on the number or qualifications of experts used to establish ground truth for the clinical (Human Factors Summative) test set. The assessment appears to be based on observed user performance and identification of critical errors, rather than expert-adjudicated diagnostic "ground truth."

4. Adjudication Method for the Test Set

The document does not specify an adjudication method (e.g., 2+1, 3+1, none) for the Human Factors Summative Study. The focus was on identifying critical errors during user interaction, which would likely be observed and documented by study facilitators/observers, rather than requiring expert adjudication of different interpretations.

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

No, a Multi-Reader Multi-Case (MRMC) comparative effectiveness study was not done. This type of study is typically used for diagnostic devices involving humans interpreting results (e.g., radiologists reading images) and comparing performance with and without AI assistance. The InPen System is a pen injector with a dose calculator, and its evaluation focused on functionality, safety, and human factors, not on improving human reader performance in a diagnostic context.

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

Yes, a form of standalone performance was implicitly done for the dose calculator component. The document states:

"The dose calculator uses the standard approach using healthcare provider specified insulin-to-carbohydrate ratio and insulin sensitivity factors for making calculations."
"In addition, the calculator includes a consideration for insulin on-board based on the published study by Mudaliar, et.al. (1999) for the duration of insulin action."

This indicates that the algorithm's calculation logic was assessed against established medical standards and a specific published clinical model, which represents a standalone evaluation of its computational accuracy and adherence to a defined medical algorithm.

7. The Type of Ground Truth Used

For biocompatibility, EMC, electrical safety, and bench testing, the ground truth was adherence to established national and international standards (ISO, IEC).
For the software verification and validation, the ground truth was adherence to FDA guidance documents for software in medical devices.
For the Human Factors Summative Study, the ground truth was the absence of "critical errors that could lead to a hazard" during patient use, as determined by observation during the study.
For the dose calculator, the ground truth for its logic was based on established medical practice/formulas (HCP-specified parameters) and a published clinical study/model (Mudaliar, et al. 1999 for insulin on-board).

8. The Sample Size for the Training Set

The document does not explicitly mention a training set sample size. The InPen System as described is a hardware device (pen injector) with a software component (app/dose calculator). The "training" for such devices typically refers to the data used during the development of the algorithms (firmware for the pen, logic for the app). This information is generally part of the internal development process and not usually reported as a "sample size" in FDA submission summaries unless a specific machine learning model with a distinct training phase is being described. Given the nature of the device (a calculator using established formulas rather than a predictive AI model trained on patient data), a traditional "training set" for an AI model may not be applicable.

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

As noted above, a distinct "training set" in the context of an AI/ML model for diagnostic or predictive purposes is not explicitly described. For the algorithmic logic of the dose calculator, the ground truth was established by:

Medical consensus/standards: The use of "healthcare provider specified insulin-to-carbohydrate ratio, and insulin sensitivity parameters." These are standard, well-accepted medical formulas.
Published clinical research: The "consideration for insulin on-board based on the published study by Mudaliar, et.al. (1999)." This study's findings served as the basis for incorporating this aspect into the calculator's logic.

Summary

{0}------------------------------------------------

Image /page/0/Picture/1 description: The image shows the logo for the U.S. Department of Health & Human Services. The logo is circular and contains the text "DEPARTMENT OF HEALTH & HUMAN SERVICES - USA" around the perimeter. In the center of the circle is an abstract symbol that resembles a stylized caduceus or a family of three people.

Food and Drug Administration 10903 New Hampshire Avenue Document Control Center - WO66-G609 Silver Spring, MD 20993-0002

July 26, 2016

Companion Medical, Inc. Mr. Jasper Benke Vice President, RA/QA 16486 Bernardo Center Drive, Suite 300 San Diego, California 92128

Re: K160629

Trade/Device Name: Inpen® System Regulation Number: 21 CFR 880.5860 Regulation Name: Piston Syringe Regulatory Class: Class II Product Code: FMF, NDC Dated: Julv 7, 2016 Received: July 8, 2016

Dear Mr. Benke:

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. 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.

{1}------------------------------------------------

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); medical device reporting (reporting of medical devicerelated adverse events) (21 CFR 803); good manufacturing practice requirements as set forth in the quality systems (OS) regulation (21 CFR Part 820); and if applicable, the electronic product radiation control provisions (Sections 531-542 of the Act); 21 CFR 1000-1050.

If you desire specific advice for your device on our labeling regulation (21 CFR Part 801), please contact the Division of Industry and Consumer Education at its toll-free number (800) 638-2041 or (301) 796-7100 or at its Internet address

http://www.fda.gov/MedicalDevices/ResourcesforYou/Industry/default.htm. 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

http://www.fda.gov/MedicalDevices/Safety/ReportaProblem/default.htm for the CDRH's Office of Surveillance and Biometrics/Division of Postmarket Surveillance.

You may obtain other general information on your responsibilities under the Act from the Division of Industry and Consumer Education at its toll-free number (800) 638-2041 or (301) 796-7100 or at its Internet address

http://www.fda.gov/MedicalDevices/ResourcesforYou/Industry/default.htm.

Sincerely yours,

Tina Kiang
-s

Tina Kiang, Ph.D. Acting Director Division of Anesthesiology. General Hospital, Respiratory, Infection Control, and Dental Devices Office of Device Evaluation Center for Devices and Radiological Health

Enclosure

{2}------------------------------------------------

Indications for Use

510(k) Number (if known) K160629

Device Name InPen System

Indications for Use (Describe)

The InPen is a home-use reusable pen injector for single-patient use by people with diabetes age 12 and older for the selfinjection of a desired dose of insulin. The pen injector is compatible with Lilly Humalog® U-100 3.0 mL cartridges of insulin and single-use detachable and disposable pen needles (not included). The pen injector allows the user to dial the desired dose from 0.5 to 30 units in one-half (1/2) unit increments.

The InPen is a home-use reusable pen injector for single-patient use by people with diabetes age 12 and older for the selfinjection of a desired dose of insulin. The pen injector is compatible with Novo Nordisk Novolog® U-100 3.0 mL cartridges of insulin and single-use detachable and disposable pen needles (not included). The pen injector allows the user to dial the desired dose from 0.5 to 30 units in one-half (1/2) unit increments.

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### 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 Companion Medical InPen® System

l. SUBMITTER

Address:	Companion Medical, Inc.16486 Bernardo Center Drive, Suite 300San Diego, California 92128
Phone:	(858) 522-0252
Contact:	Mr. Jasper Benke
Date Prepared:	July 26, 2016

ll. DEVICE

Name of Device:	InPen® System
Common Name:	Pen Injector with Dose Calculator

Classification Name: Piston Syringe Classification Regulation: (21 CFR §880.5860); Class II Product code: FMF, NDC

III. PREDICATE DEVICES

NovoPen® Echo (K123766) ACCU-CHEK® Bolus Advisor (K150910)

These predicates have not been subject to a design-related recall. No reference devices were used in this submission.

IV. DEVICE DESCRIPTION

The InPen System consists of a manually-controlled pen injector and an app containing a logbook and a dose (bolus) calculator.

{4}------------------------------------------------

V. INDICATIONS FOR USE

The InPen is a home-use reusable pen injector for single-patient use by people with diabetes age 12 and older for the self-injection of a desired dose of insulin. The pen injector is compatible with Novo Nordisk Novolog® U-100 3.0 mL cartridges of insulin and single-use detachable and disposable pen needles (not included). The pen injector allows the user to dial the desired dose from 0.5 to 30 units in one-half (1/2) unit increments.

VI. COMPARISON OF TECHNOLOGICAL CHARACTERISTICS WITH THE PREDICATE DEVICE

The InPen pen injector is substantially equivalent to other legally marketed pen injectors. Specifically, the InPen pen injector is substantially equivalent to the Novo Nordisk NovoPen Echo® (K123766) cleared on August 15, 2013. The InPen pen injector has the same intended use and similar indications, technological characteristics, and principles of operation as the previously cleared predicate device. A substantial equivalence chart comparing the similarities and differences between the InPen pen injector and its predicate device is shown in Table 1. The minor differences in technological characteristics do not raise new questions of safety or effectiveness. The differences in indications for use (patient age, insulin type) do not change the intended use, or raise new questions of safety and effectiveness; the subject patient age is a limitation of the predicate device patient age, thus the risk margin is decreased. The additional insulin type does not change the intended use, or raise new questions of safety and effectiveness as the insulin types are the same concentration, and marketed as comparable therapeutically.

{5}------------------------------------------------

Attribute	Subject Device	Predicate Device
	InPen Pen Injector	NovoPen Echo (K123766)
Classification	(Class II - FMF - 21 CFR §880.5860)	Same
Indications For Use	The InPen is a home-use reusablepen injector for single-patient useby people with diabetes age 12and older for the self-injection of adesired dose of insulin. The peninjector is compatible with LillyHumalog® U-100 / Novo NordiskNovolog® 3.0 mL cartridges ofinsulin and single-use detachableand disposable pen needles (notincluded). The pen injector allowsthe user to dial the desired dosefrom 0.5 to 30 units in one-half(1/2) unit increments.	The Novo Pen Echo is a re-usablepen injector designed for single-patient use by diabetics for theself-injection of a desired dose ofinsulin. The pen injector usesPenFill 3.0 mL cartridges of NovoNordisk insulin and a single usedetachable and disposable penneedle (supplied separately). Thepen injector allows the user to dialthe desired dose from 0.5 to 30units in one half (1/2) unitincrements.
Cartridge Volume	3 ml (300 units)	Same
Drug	U-100 insulin	Same
Syringe Type	Piston Syringe	Same
Single Patient Use	Yes	Same
Reusable Device	Yes	Same
Dose Accuracy	Meets ISO 11608-1 requirements	Same
Biocompatibility	Meets ISO 10993-1 requirements	Same
Maximum Dose	30 Units	Same
User Feedback	Audible and tactile clicksper increment	Same
Dose Dialing	Two-way	Same
Battery	Non-rechargeable	Same
Electronics	Folded Flex Circuit	Same
Software	Yes	Same
Dose Delivery	Mechanical	Same
Unit Increments	Half-Unit incrementsafter 0.5 Unit	Same
Dimensions	6.5" x ø0.6"	6.4" x ø0.7"
Weight	35 grams	51 grams
Fluid Pathway	None	Same
Contact
Dose History	Full; Displayed on app	Last Dose; Displayed on device
Dose Calculator	Yes	No
Communication
Attribute	Subject DeviceInPen Dose Calculator	Predicate DeviceACCU-CHEK® Bolus Advisor(K150910)
Classification	(Class II - NDC - 21 CFR §868.1890)	Same
Indications For Use	The InPen dose calculator, acomponent of the InPen app, isindicated for the management ofdiabetes by people with diabetesage 12 and older by calculating aninsulin dose or carbohydrate intakebased on user entered data. Priorto use, a healthcare professionalmust provide the patient-specifictarget blood glucose, insulin-to-carbohydrate ratio, and insulinsensitivity parameters to beprogrammed into the software.	The ACCU-CHEK Bolus Advisor, asa component of the ACCUCHEKConnect Diabetes ManagementApp, is indicated for themanagement of diabetes bycalculating an insulin dose orcarbohydrate intake based onuser entered data. Before its use,a physician or healthcareprofessional must activate thebolus calculator and provide thepatient-specific target bloodglucose, insulin-to-carbohydrateratio, and insulin sensitivityparameters to be programmedinto the software.
Prescription use?	Yes	Same
User Group	Diabetes patients treated withmultiple daily insulin injection(MDI) therapy	Same
Communication withinsulin pumps	No	Same
Software Level ofConcern	Major	Same
Wireless Connectivity	Bluetooth Low Energy (BLE)	Same
Control or affectblood glucosemeasurements?	No	Same
Control or affectinsulin delivery?	No	Same
Attribute	Subject DeviceInPen Dose Calculator	Predicate DeviceACCU-CHEK® Bolus Advisor(K150910)
Reports, graphs, andElectronic Log Book	Yes	Same
CarbohydrateCalculator	Calculates carbohydrate intakebased on user-entered data	Same
Manual Dose Entry	Yes	Same
InPen Dose Entry	Yes	No
Tracking of residualbolus insulin tomitigate stacking	Yes	Same
Operatingplatform	iOS platform	Same
UI Standards	iOS standards	Same

{6}------------------------------------------------

The InPen app is substantially equivalent to other legally marketed dose calculators. Specifically, the InPen app is substantially equivalent to the Roche ACCU-CHEK® Bolus Advisor (K150910) cleared on June 3, 2015. The InPen app has the same intended use and similar indications, technological characteristics, and principles of operation as the previously cleared predicate device. A substantial equivalence chart comparing the similarities and differences between the InPen pen injector and its predicate device is shown in Table 2. The minor differences in technological characteristics do not raise new questions of safety or effectiveness. The difference in indications for use (patient age) does not change the intended use, or raise new questions of safety and effectiveness, as the subject patient age is a limitation of the predicate device patient age, thus the risk margin is decreased.

Table 2

{7}------------------------------------------------

VII. Performance Data

Biocompatibility

The InPen System has been evaluated for biocompatibility according to ISO 10993-1 Biological Evaluation of Medical Devices - Part 1: Evaluation and Testing. The InPen System does not contact any part of the insulin fluid path. The patient contacting materials were identified and tested as a limited duration (≤ 24 hours), surface device, with skin contact. The following assays were completed:

. Cytotoxicity
Sensitization .
. Irritation / Intracutaneous Reactivity

The InPen System is considered biocompatible and acceptable for use.

Electromagnetic Compatibility and Electrical Safety

The InPen System has been tested and shown to comply with the electrical safety and electromagnetic compatibility requirements in IEC 60601-1 Medical Electrical Equipment, Part 1: General Requirements For Basic Safety And Essential Performance and IEC 60601-1-2 – Medical Electrical Equipment - Part 1-2: General Requirements For Basic Safety And Essential Performance - Collateral Standard: Electromagnetic Compatibility - Requirements And Tests.

Additionally, the InPen System complies with IEC 60601-1-11 Medical Electrical Equipment -Part 1-11: General Requirements For Basic Safety And Essential Performance - Collateral Standard: Requirements For Medical Electrical Equipment And Medical Electrical Systems Used In The Home Healthcare Environment.

{8}------------------------------------------------

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, "Guidance for the Content of Premarket Submissions for Software Contained in Medical Devices." The software for this device was considered as a "major" level of concern, since a failure or latent flaw in the software could directly result in serious injury or death to the patient or operator.

Bench Testing

The InPen System has been shown to meet the requirements of ISO 11608-1, Needle-Based Injection Systems For Medical Use - Requirements And Test Methods - Part 1: Needle-Based Injection Systems and Part 2:Needles. Where appropriate, requirements were modified to reflect ISO 11608-4, Pen-Injectors For Medical Use -- Part 4: Requirements And Test Methods For Electronic And Electromechanical Pen-Injectors. Testing was completed for general design requirements, mechanical characterization, and dose accuracy. In all instances, the InPen System functioned as intended and met the acceptance criteria.

Clinical Evidence

Companion Medical has demonstrated the InPen System is appropriate for its intended use through the use of hazard analysis according ISO 14971. Verification and validation of the user interface was completed through a series of Formative Studies and a comprehensive Human Factors Summative Study. In the Summative Study, patients with sufficient diabetes knowledge completed self-training and then completed a series of critical tasks using the InPen System. The Summative Study demonstrated that after self-training, patients are able to use the InPen System without making critical errors that could lead to a hazard. No new use-related hazards were identified during the study. The InPen System satisfies all functional performance and safety requirements, meets its intended use, and is safe for the intended user population. Substantial equivalence was based in part on the study.

The dose calculator uses the standard approach using healthcare provider specified insulin-tocarbohydrate ratio and insulin sensitivity factors for making calculations. In addition, the calculator includes a consideration for insulin on-board based on the published study by Mudaliar, et.al. (1999) for the duration of insulin action.

VIII. CONCLUSIONS

The subject device is substantially equivalent to the predicate devices, as demonstrated by performance data. It has the same intended use/indications for use, and substantially equivalent technological characteristics and principles of operation.

Regulation Number and Section

§ 880.5860 Piston syringe.

(a)
Identification. A piston syringe is a device intended for medical purposes that consists of a calibrated hollow barrel and a movable plunger. At one end of the barrel there is a male connector (nozzle) for fitting the female connector (hub) of a hypodermic single lumen needle. The device is used to inject fluids into, or withdraw fluids from, the body.(b)
Classification. Class II (performance standards).