PeriCALM Patterns is intended for use to provide additional secondary information as an adjunct to qualified clinical decision-making during antepartum or intrapartum obstetrical monitoring at ≥32 weeks gestation for annotation and summary of the fetal heart rate recording for baseline, accelerations and the uterine pressure recording for contractions.

WARNING: Evaluation of FHR during labor and patient management decisions should not be based solely on PeriCALM Patterns annotations or summaries and should include inspection of the fetal monitor tracing and consideration of all pertinent clinical information.

Device Description

PeriCALM Patterns 3.0 is a software device to be used with fetal/maternal monitoring systems. The subject device is a software algorithm to detect, label and measure features (accelerations, decelerations, baseline, and contractions) in electronic fetal monitoring (EFM) records. PeriCALM Patterns 3.0 uses fetal monitor data imported through an interface with an external source or with a third-party clinical information system. PeriCALM Patterns can function in a networked environment or as a standalone workstation.

The subject device includes present-day Long and Short-Term Memory (LSTM) neural networks to identify segments of a fetal heart rate tracing corresponding to accelerations, decelerations, baseline as well as uninterpretable segments where is missing tracing. Contraction detection is achieved using the same processes as the predicate device.

AI/ML Overview

Here's a breakdown of the acceptance criteria and the study proving the device meets them, based on the provided text:

1. Table of Acceptance Criteria and Reported Device Performance

Metric / Parameter	Acceptance Criteria (Non-inferiority Margin)	Reported Device Performance
Acceleration & Deceleration Detection
Sensitivity (Se)	Non-inferiority margin of 15% (Device performance not significantly worse than 15% of Clinician Readers' Se) for 12 co-primary endpoints (Term & Preterm)	Passed all acceptance criteria for performance testing regarding pattern detection. (Specific values not provided in the text, but the study "passed all acceptance criteria").
Specificity (Sp)	Non-inferiority margin of 15% (Device performance not significantly worse than 15% of Clinician Readers' Sp) for 12 co-primary endpoints (Term & Preterm)	Passed all acceptance criteria for performance testing regarding pattern detection.
Positive Predictive Value (PPV)	Non-inferiority margin of 15% (Device performance not significantly worse than 15% of Clinician Readers' PPV) for 12 co-primary endpoints (Term & Preterm)	Passed all acceptance criteria for performance testing regarding pattern detection.
FHR Baseline Measurements
Bias (Mean difference)	Non-inferiority margin of 10% (for 4 co-primary endpoints)	Passed all acceptance criteria for performance testing regarding pattern detection. (Specific values not provided)
95% CI of Bias	≤ 5 bpm (for 4 co-primary endpoints)	Passed all acceptance criteria for performance testing regarding pattern detection. (Specific values not provided, but the study "passed all acceptance criteria"). The text states, "The acceptance criteria for 95% CI of Bias for the subject device was set to threshold of ≤ 5 bpm."

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

Sample Size: A total of 70 subjects were used in the study, with one tracing per subject. This included 30 preterm subjects and 40 term subjects.
Data Provenance: Tracings were obtained from hospitals using a variety of fetal monitor models and manufacturers (Corometrics 170, 250 series by GE HealthCare, Avalon FM50 and FM40 by Philips Medical, and S1 from Neoventa). The study was retrospective. The specific country of origin is not explicitly stated, but PeriGen, Inc. is located in Israel, however, the data provenance is through collaborations with US Hospitals through various monitor OEMs.

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

Number of Experts: 3 experts (referred to as "Truthers") were used.
Qualifications: They were specified as "a panel of 3 experts." While the specific medical specialty (e.g., Obstetrician) is implied by the context of "fetal heart rate tracings" and "obstetrical monitoring," their exact qualifications (e.g., years of experience, specific board certifications) are not detailed in the provided text.

4. Adjudication Method for the Test Set Ground Truth

Adjudication Method: A majority opinion approach was used to resolve inter-observer variation among the 3 experts.

5. Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study

Yes, an MRMC study was done. The study design is described as "a retrospective study with multi-reader/multi-case technique."
Effect Size of Human Readers' Improvement with AI vs. Without AI Assistance: The study's primary objective was to demonstrate the non-inferiority of the device (PeriCALM Patterns 3.0) to a set of qualified and experienced Obstetrician Gynecologists (Clinician Readers) in terms of pattern detection and baseline measurement. It does not describe a study where human readers were assisted by AI and then compared to human readers without AI assistance. Therefore, an effect size of human improvement with AI assistance is not reported in this text.

6. Standalone (Algorithm Only Without Human-in-the-Loop Performance) Study

Yes, implicitly. The study compared the "performance of PeriCALM Patterns 3.0" directly to "Ground Truth" and "Clinician Readers." This suggests the algorithm's performance was evaluated in isolation (without human interaction) in comparison to both human consensus and individual human expert performance. The metrics (Sensitivity, Specificity, PPV, Bias, LoA) are typical of standalone algorithm evaluations.

7. Type of Ground Truth Used

Expert Consensus: The ground truth for this study was established by a panel of 3 experts, with a majority opinion approach used to resolve inter-observer variation.

8. Sample Size for the Training Set

The provided text does not specify the sample size used for the training set. It only describes the test set.

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

The provided text does not specify how the ground truth for the training set was established. It only describes the ground truth establishment for the test set.

Summary

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Image /page/0/Picture/0 description: The image shows 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 logo on the right. The FDA logo features the letters "FDA" in a blue square, followed by the words "U.S. FOOD & DRUG ADMINISTRATION" in blue text.

January 10, 2025

PeriGen, Inc. Candace Alva Director of Regulatory Affairs and Quality Assurance Sderot Nim 2, P.O. Box 110 Rishon LeTziyon, 7510002 Israel

Re: K241009

Trade/Device Name: PeriCALM Patterns 3.0 Regulation Number: 21 CFR§ 884.2740 Regulation Name: Perinatal Monitoring System and Accessories Regulatory Class: II Product Code: HGM Dated: December 11, 2024 Received: December 11, 2024

Dear Candace Alva:

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.

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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).

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); 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-safety-reportingcombination-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.

All medical devices, including Class I and unclassified devices and combination product device constituent parts are required to be in compliance with the final Unique Device Identification System rule ("UDI Rule"). The UDI Rule requires, among other things, that a device bear a unique device identifier (UDI) on its label and package (21 CFR 801.20(a)) unless an exception or alternative applies (21 CFR 801.20(b)) and that the dates on the device label be formatted in accordance with 21 CFR 801.18. The UDI Rule (21 CFR 830.300(a) and 830.320(b)) also requires that certain information be submitted to the Global Unique Device Identification Database (GUDID) (21 CFR Part 830 Subpart E). For additional information on these requirements, please see the UDI System webpage at https://www.fda.gov/medical-device-advicecomprehensive-regulatory-assistance/unique-device-identification-system-udi-system.

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.

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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,

Monica D. Garcia -S

Monica D. Garcia, Ph.D. Assistant Director DHT3B: Division of Reproductive, Gynecology and Urology Devices OHT3: Office of GastroRenal, ObGyn, General Hospital and Urology Devices 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) K241009

Device Name PeriCALM Patterns 3.0

Indications for Use (Describe)

PeriCALM Patterns is intended for use to provide additional secondary information as an adjunct to qualified clinical decision-making during antepartum or intrapartum obstetrical monitoring at _32 weeks gestation for annotation and summary of the fetal heart rate recording for baseline, accelerations and the uterine pressure recording for contractions.

	Type of Use (Select one or both, as applicable)

X Prescription Use (Part 21 CFR 801 Subpart D)

Over-The-Counter Use (21 CFR 801 Subpart C)

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Image /page/4/Picture/0 description: The image shows the logo for PeriGen, a company specializing in advanced perinatal systems. The logo features the company name in a teal sans-serif font, with the "P" extending into a partial red circle on the left side. Below the name, in a smaller font, are the words "Advanced Perinatal Systems."

510(k) Summary PeriCALM Patterns 3.0 - K241009

Date Summary Prepared:	January 10, 2025
Submitter Information
Submitted by:	PeriGen Solutions, LtdSderot Nim 2, PO Box 110,Rishon LeTziyon,7510002, Israel
Telephone:	+972-3-905-9900
Contact Person:	Natan BlanksGM, Israel Operations
Subject Device Information
Device Trade Name:	PeriCALM Patterns 3.0
Common Name:	Computer-based information management system forobstetrical care
Regulation Name:	Perinatal monitoring system and accessories
Regulation Number	21 CFR 884.2740
Device Panel:	Obstetrics/Gynecology
Product code:	HGM (system, monitoring, perinatal)
Regulatory Class:	II
Predicate Device Information
Predicate Device:	CALM Patterns PeriGen Solutions, Ltd. (Also listed asPeriCALM Patterns)
	The predicate device has not been subject to a design-related recall
510(k) Number	K040788
Device Description

PeriGen Solutions Ltd.

Azrieli Rishonim | 2 Nim Blvd. POB 110 Rishon LeZion 7510002 Israel

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Image /page/5/Picture/1 description: The image shows the logo for PeriGen, a company that specializes in advanced perinatal systems. The word "PeriGen" is written in a combination of blue and red colors, with the "i" in "PeriGen" being replaced by a red arc. Below the company name, the words "Advanced Perinatal Systems" are written in a smaller, gray font.

Indications for Use

Comparison of Intended Use and Technological Characteristics of the Subject and Predicate Device	Subject DevicePeriGen – PeriCALM Patterns3.0K241009	Predicate DevicePeriGen - PeriCALMPatternsK040788
Intended Use	PeriCALM Patterns is intended foruse to provide additionalsecondary information as anadjunct to qualified clinicaldecision-making duringantepartum or intrapartumobstetrical monitoring at ≥32weeks gestation for analysis of thefetal heart rate recording forbaseline, accelerations anddecelerations and the uterinepressure recording forcontractions.WARNING: Evaluation of FHRduring labor and patientmanagement decisions should notbe based solely on PeriCALMPatterns annotations or summariesand should include inspection ofthe fetal monitor tracing andconsideration of all pertinentclinical information.	CALM Patterns is intended foruse as an adjunct to qualifiedclinical decision-making duringantepartum or intrapartumobstetrical monitoring at ≥36weeks gestation to obtainannotation of the FHR forbaseline, accelerations, anddecelerations.WARNING: Evaluation of FHRduring labor and patientmanagement decisions should notbe based solely on CALMPatterns annotations.
Applicable gestational age	≥32 weeks	≥36 weeks
Data Collection	Collects FHR and uterine activitydata from electronicmaternal/fetal monitors.	Collects FHR and uterineactivity data from electronicmaternal/fetal monitors.
Sample Rate	Samples FHR at a minimum offour samples per second. Samplesuterine activity at a minimum or 1sample per second	Samples FHR at a minimum offour samples per second. Samplesuterine activity at a minimum or 1sample per second

PeriGen Solutions Ltd.

Azrieli Rishonim | 2 Nim Blvd. POB 110 Rishon LeZion 7510002 Israel

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Pattern recognition module coretechnology	Signal processing and neuralnetworks	Signal processing and neuralnetworks
Neural network interference:combined accel-decel-baseline+ non-interpretable detection	Yes	No
Measurement and labelingaccelerations on the tracing	Yes	Yes
Baseline measurements	Yes	Yes
Contraction measurements	Yes	Yes
Analysis provided andsummarized in time intervals	15 or 30 minutes	20 minutes
Provides users with the option toselect, modify and export a set ofsummarized measurements.	Yes	Yes
Displays a long-termcompressed view of tracing	Yes	Yes
Summarizes measurements withthe long-term view.	Yes	Yes
Handling of disagreementsbetween algorithm detectedpatterns and clinician opinion	User can delete a featureannotation	User can add, modify or delete afeature annotation.
Non-interpretable segmentswhere there is missing tracing	Yes	No

The indications for use of PeriCALM Patterns 3.0 are similar to the predicate device and the subject and predicate device have the same intended use - as an adjunct to clinical decision making during antepartum, or intrapartum monitoring. The subject device has an extended gestational age from > 32 weeks, compared to the predicate device which has a gestational age from ≥ 36 weeks. This difference in gestational age does not raise different questions of safety and effectiveness.

The technological differences between the subject and predicate device include the addition of neural network interference (combined accel-decel-baseline + non-interpretable detection), different time intervals of analysis, and differences in the managements of non-interpretable segments for a missing trace. These differences do not raise different questions of safety and effectiveness as compared to the predicate device.

Summary of Non-clinical Performance Testing

Software and Cybersecurity

Perinatal Systems

Software was evaluated as recommended in the 2023 FDA guidance document "Content of Premarket Submissions for Device Software Functions." The following activities were successfully completed:

Risk Analysis / Management
Requirements Reviews ●
Design Reviews ●
Software Verification and Validation

PeriGen Solutions Ltd.

Azrieli Rishonim | 2 Nim Blvd. POB 110 Rishon LeZion 7510002 Israel

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Image /page/7/Picture/1 description: The image shows the logo for PeriGen. The logo consists of the word "PeriGen" in blue text, with the "P" partially enclosed by a red semi-circle. Below the word "PeriGen" are the words "Advanced Perinatal Systems" in a smaller font size.

The successful V&V tests demonstrate that the device performs in accordance with specifications. Cybersecurity was evaluated as recommended in the 2023 FDA guidance document "Cybersecurity in Medical Devices: Quality System Considerations and Content of Premarket Submissions."

Summary of Clinical Performance Testing

A retrospective study with multi-reader/multi-case technique was used to determine if the performance of PeriCALM Patterns 3.0 is not inferior to that of a set of qualified and experienced Obstetrician Gynecologists called the Clinician Readers. The predicate device was cleared for use in gestational ages of ≥36 weeks comparing to Ground Truth and Clinician Readers. The same approach was taken for this study, comparing PeriCALM Patterns 3.0 to Ground Truth and Clinician Readers for two gestational age subgroups: ≥36 weeks (term) and 32-35 weeks (pre-term). The ground truth for this study is established by a panel of 3 experts, called the "Truthers". To resolve the inter-observer variation, a majority opinion approach was used. The results of the comparison of the subject device to ground truth is to be non-inferior to the results of the comparison of Readers to ground truth.

A total of 70 subjects (30 preterm and 40 term), with one tracing per subject, were used in the study. Tracings were obtained from hospitals using a variety of fetal monitor models and manufacturers including Corometrics 170, 250 series by GE HealthCare, Avalon FM50 and FM40 by Philips Medical, and S1 from Neoventa and included both antepartum and intrapartum recordings. The tracings were selected from pregnancies with gestational ages from 32 weeks to term, covering a wide range of operating and clinical conditions with respect to maternal BMI, delivery modes, fetal birth weights, hospital types, Apgar scores and antepartum or intrapartum usage.

The study included sixteen (16) co-primary endpoints with different acceptance criteria for noninferiority. Twelve (12) co-primary endpoints pertained to accelerations and decelerations for both gestational groups (i.e., Term and Preterm) and included performance metrics (Sensitivity (Se), Specificity (Sp), Positive Predictive Value (PPV)) of the subject device compared to those of the Readers. Remaining four co-primary endpoints focused on the FHR baseline measurements and were based on Bland-Altman analyses to determine bias, the mean difference between two methods and the Limits of Agreement (LoA) which include 95% of the differences between the two measurement methods. Inferiority margin of 15% for acceleration and deceleration detection and 10% for baseline level was used. The acceptance criteria for 95% CI of Bias for the subject device was set to threshold of ≤ 5 bpm.

PeriCALM Patterns 3.0 passed all acceptance criteria on performance testing regarding pattern detection.

Conclusion

The performance data described above demonstrate that the PeriCALM Patterns 3.0 is as safe and effective as the PeriCALM Patterns (K040788) and supports a determination of substantial equivalence.

Regulation Number and Section

§ 884.2740 Perinatal monitoring system and accessories.

(a)
Identification. A perinatal monitoring system is a device used to show graphically the relationship between maternal labor and the fetal heart rate by means of combining and coordinating uterine contraction and fetal heart monitors with appropriate displays of the well-being of the fetus during pregnancy, labor, and delivery. This generic type of device may include any of the devices subject to §§ 884.2600, 884.2640, 884.2660, 884.2675, 884.2700, and 884.2720. This generic type of device may include the following accessories: Central monitoring system and remote repeaters, signal analysis and display equipment, patient and equipment supports, and component parts.(b)
Classification. Class II (performance standards).