Natural Cycles is a stand-alone software application, intended for women 18 years and older, to monitor their fertility. Natural Cycles can be used for preventing a pregnancy (contraception) or planning a pregnancy (conception).

Device Description

Natural Cycles is an over-the-counter web and mobile-based standalone software application that monitors a woman's menstrual cycle using information entered by the user and informs the user about her past, current and future fertility status. The following information is used by the Natural Cycles software:

daily body temperature measurements
information about the user's menstruation cycle (i.e., start date, number of days)
optional ovulation or pregnancy test results
A proprietary algorithm evaluates the data and returns the user's fertility status.
Natural Cycles is available in three modes: Contraception, and Pregnancy. For Contraception mode, the device provides predictions of "not fertile," shown as green days, and "use protection," shown as red days, that allow the user to determine the days on which her risk of conception is highest, and then make choices about either abstaining from sex or using a barrier method of contraception to prevent pregnancy.
In addition to measuring daily basal body temperature with an oral thermometer with two decimal points, the device allows automatic temperature input from the Oura ring, a wearable temperature monitor.
Natural Cycles can be used by women 18 years and older. Women who have been on hormonal birth control within 60 days prior to using Natural Cycles have a higher risk of becoming preqnant when compared to women who have not been on hormonal birth control within the 12 months prior to using the device may not be right for women who have a medical condition where pregnancy would be associated with a significant risk to the mother or the fetus.

AI/ML Overview

Here's a breakdown of the acceptance criteria and study proving the device meets them, based on the provided FDA 510(k) summary for Natural Cycles (K202897):

1. Table of Acceptance Criteria and Reported Device Performance

The primary purpose of this 510(k) submission was to add the Oura ring as a new temperature input method for the Natural Cycles algorithm. Therefore, the acceptance criteria and performance data revolve around demonstrating that this new input method does not negatively impact the algorithm's contraceptive effectiveness.

Acceptance Criteria (Implicit)	Reported Device Performance
Algorithm Performance Equivalence: The Natural Cycles algorithm, when using Oura ring temperature input, must maintain its ability to accurately identify ovulation and determine fertility status for contraception, comparable to using oral thermometer input, without increasing the risk of unintended pregnancy.	"the Natural Cycles algorithm was able to identify that ovulation had occurred, which was confirmed in the study by comparison to the 87 positive LH test results." (This indicates the core function of identifying ovulation was maintained). "Compared to the two-decimal place oral thermometer, the Natural Cycles algorithm provides additional 1.6 green days (not fertile) in the luteal phase of the menstrual cycle when the input temperature was from the Oura ring, without increasing the risk of unintended pregnancy." (This directly addresses the equivalence in contraceptive effectiveness by showing more "green days" without higher pregnancy risk, implying no decrease in safety/effectiveness).
Usability/Human Factors (Implicit for integration): The integration of Oura ring data should be seamless and not introduce new usability issues that compromise safety or effectiveness. (While not explicitly stated as a criterion, it's generally an underlying expectation for new input methods).	"Human factors testing in DEN170052 was used to support that device users could safely use the device." (This refers to prior human factors testing for the predicate device, implying that the general usability of Natural Cycles for temperature input was already established, and the Oura integration implicitly rode on this). The study design, with participants being "experienced users of both Natural Cycles and entering their daily temperature using an oral thermometer but did not have experience using the Oura ring with Natural Cycles," suggests that the focus was on the data integration, not on the fundamental usability of the app itself.
Software Compliance & Cybersecurity: The software handling Oura ring data must conform to regulatory standards.	"- Software documentation provided in accordance with the 2005 FDA guidance document Guidance for the Content of Premarket Submissions for Software Contained in Medical Devices to support device software with a major level of concern. - Cybersecurity information provided in accordance with the 2014 FDA guidance document ● Content of Premarket Submissions for Management of Cybersecurity in Medical Devices." (These directly state compliance with relevant software and cybersecurity guidelines.)

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

Sample Size for Test Set: 40 women.
Data Provenance:
- Country of Origin: The majority (38) of the women were located in Sweden, with one each in the US and Switzerland.
- Retrospective or Prospective: Prospective. The study involved current data collection from participants wearing the Oura ring and using an oral thermometer over multiple menstrual cycles.

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

The document does not mention the use of human experts to establish ground truth for this specific clinical study. The ground truth for identifying ovulation was established by:

Objective Physiological Markers: Luteinizing Hormone (LH) tests. Participants were asked to record the results of LH tests.
Algorithmic Confirmation: The Natural Cycles algorithm's determination of ovulation.

The study aimed to compare the algorithm's performance with two different temperature inputs (oral thermometer vs. Oura ring) against an objective biological marker (LH tests).

4. Adjudication Method for the Test Set

No explicit adjudication method is described, as the ground truth was based on LH test results and the algorithm's determination, rather than subjective expert interpretations.

5. If a Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study was done

No, an MRMC comparative effectiveness study was not done. This study focused on comparing the performance of the algorithm with different data inputs (Oura ring vs. oral thermometer) in determining fertility status, using LH tests for validation. It did not involve multiple human readers assessing cases with and without AI assistance.

6. If a Standalone (i.e., algorithm only without human-in-the-loop performance) was done

Yes, a standalone study was done. The study "was conducted to compare the daily temperatures generated by a wearable temperature monitor, the Oura ring, to a two decimal place oral thermometer for use by the NaturalCycles algorithm." The outcome measured was the algorithm's ability to identify ovulation and determine fertility status based on these inputs, and how the "green days" (not fertile) differed, without increasing the risk of unintended pregnancy. The human "in the loop" was the user providing the temperature data, but the performance being assessed was the algorithm's interpretation of that data.

7. The Type of Ground Truth Used

The primary ground truth used was:

Luteinizing Hormone (LH) Test Results: Used to confirm ovulation occurrence (87 positive LH test results were submitted).
Implied Clinical Outcome (Contraceptive Effectiveness): The statement "without increasing the risk of unintended pregnancy" refers to the overall clinical effectiveness as proven by prior studies of the Natural Cycles algorithm itself (likely referenced in the predicate device’s submission DEN170052), which this study aimed to maintain.

8. The Sample Size for the Training Set

The document does not specify the sample size for the training set for the Natural Cycles algorithm. It states, "There have been no changes to how the Natural Cycles algorithm determines the daily fertility status," implying the core algorithm was trained and validated prior to this submission (likely as part of the predicate device DEN170052). This submission focuses on validating a new input source for an existing, unchanged algorithm.

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

Since the document does not provide details on the training set, it does not specify how its ground truth was established. However, for a fertility tracking algorithm, the ground truth for training would typically involve:

Large datasets of menstrual cycles: Including daily basal body temperature, menstruation dates, and confirmed ovulation dates.
Confirmation of ovulation: Often through methods like ultrasound, blood hormone levels (e.g., progesterone for luteal phase confirmation), and LH tests.
Pregnancy outcomes: For contraceptive effectiveness studies.

The detailed methods for the original algorithm's training and ground truth establishment would be found in the 510(k) submission for the predicate device, DEN170052. This current submission (K202897) is an update validating a new data input source for an already cleared and validated algorithm.

Summary

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June 24, 2021

Natural Cycles Nordic AB % Sheila Hemeon-Heyer, JD, RAC President Heyer Regulatory Solutions LLC 125 Cherry Lane Amherst, MA 01002

Re: K202897

Trade/Device Name: Natural Cycles Regulation Number: 21 CFR§ 884.5370 Regulation Name: Software Application for Contraception Regulatory Class: II Product Code: PYT Dated: May 17, 2021 Received: May 17, 2021

Dear Sheila Hemeon-Heyer:

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.

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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 803) for devices or postmarketing safety reporting (21 CFR 4, Subpart B) for combination products (see https://www.fda.gov/combination-products/guidance-regulatoryinformation/postmarketing-safety-reporting-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 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,

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

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Indications for Use

510(k) Number (if known) K202897

Device Name

Natural Cycles

Indications for Use (Describe)

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

Registration Use (Part 21 CFR 201.321 Subpart D)
Over-The-Counter Use (21 CFR 201.66 Subpart C)

__ Prescription Use (Part 21 CFR 801 Subpart D)

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

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510(k) Summary K202897 - Natural Cycles

A. Submitter: NaturalCycles Nordic AB St Eriksqatan 63B 112 34 Stockholm, Sweden Contact: Raoul Scherwitzl, PhD, CEO and Co-Founder
Phone: +46 707174866 E-mail: Raoul.scherwitzl@naturalcycles.com
B. Correspondent: Hever Requlatory Solutions LLC 125 Cherry Lane Amherst, MA 01002
Contact: Sheila Hemeon-Heyer E-mail: Sheila@heyer-requlatory.com
C. Date Prepared: June 23, 2021

Device Name and Classification Information: D.

Trade Name:	Natural Cycles
Common Name:	Software application for contraception
Regulation Name:	Software application for contraception
Regulation Number:	21 CFR 884.5370
Regulatory Class:	II
Product Code:	PYT (Device, fertility diagnostic, contraceptive, software application)

E. Predicate Device(s): DEN170052 Natural Cycles
The predicate device has not been subject to a design-related recall.

F. Device Description:

daily body temperature measurements
information about the user's menstruation cycle (i.e., start date, number of days)
optional ovulation or pregnancy test results ●

A proprietary algorithm evaluates the data and returns the user's fertility status.

Natural Cycles is available in three modes: Contraception, and Pregnancy. For Contraception mode, the device provides predictions of "not fertile," shown as green days, and

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"use protection," shown as red days, that allow the user to determine the days on which her risk of conception is highest, and then make choices about either abstaining from sex or using a barrier method of contraception to prevent pregnancy.

In addition to measuring daily basal body temperature with an oral thermometer with two decimal points, the device allows automatic temperature input from the Oura ring, a wearable temperature monitor.

Natural Cycles can be used by women 18 years and older. Women who have been on hormonal birth control within 60 days prior to using Natural Cycles have a higher risk of becoming preqnant when compared to women who have not been on hormonal birth control within the 12 months prior to using the device may not be right for women who have a medical condition where pregnancy would be associated with a significant risk to the mother or the fetus.

G. Indications for Use Statement

H. Comparison with Predicate Device

A detailed comparison of the intended use and technological features of the subject and predicate device are described in the table below:

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Parameter	Subject DeviceNatural CyclesK202897	Predicate DeviceNatural CyclesDEN 170052	Comparison
Indications forUse Statement	Natural Cycles is a stand-alone software application,intended for women 18years and older, to monitortheir fertility.Natural Cycles can beused for preventing apregnancy (contraception)or planning a pregnancy(conception).	Natural Cycles is a stand-alone software application,intended for women 18years and older, to monitortheir fertility.Natural Cycles can beused for preventing apregnancy (contraception)or planning a pregnancy(conception).	Identical
UseEnvironment	App is downloaded touser's smartphone andused in the homeenvironment	App is downloaded touser's smartphone andused in the homeenvironment	Identical
InputInformation	• Manual input of two-decimal daily basal bodytemperature (BBT)measurements orautomatic input from theOura ring.• Manual input ofinformation about theuser's menstruationcycle, i.e. start date,number of days.• Optional manual inputof ovulation orpregnancy test results.	• Manual input of two-decimal daily basalbody temperature(BBT) measurements.• Manual input ofinformation about theuser's menstruationcycle, i.e. start date,number of days.• Optional manual inputof ovulation orpregnancy test results.	Expandedoption for anew source ofdaily basalbodytemperatureinformation.

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OutputInformation	• Prevent mode: For eachday, whether the womanis fertile (red) or non-fertile (green), withdescriptive texts.• Plan mode: Fertilitystatus results aredisplayed as a scale forfertile days, and greenfor non-fertile days,together with descriptiontexts.• Pregnancy mode:Provides educationalinformation about theprogress of thepregnancy.	• Prevent mode: Foreach day, whether thewoman is fertile (red) ornon-fertile (green), withdescriptive texts.• Plan mode: Fertilitystatus results aredisplayed as a scalefor fertile days, andgreen for non-fertiledays, together withdescription texts.• Pregnancy mode:Provides educationalinformation about theprogress of thepregnancy.	Identical
	• All uses in Preventmode or Plan modereceive the ovulationdate for the month anddaily statement offertility status. Historicdata is available for allusers.	• All uses in Preventmode or Plan modereceive the ovulationdate for the month anddaily statement offertility status. Historicdata is available for allusers.

The subject and predicate device have identical indications for use statements and have the same intended use - to predict fertile and non-fertile days for use in providing patient-specific recommendations related to contraception. The subject and predicate device have different technological characteristics (i.e., temperature data input sources). This difference does not raise different questions of safety and effectiveness as compared to the predicate device.

Summary of Non-Clinical Performance Testing l.

. Software documentation provided in accordance with the 2005 FDA guidance document Guidance for the Content of Premarket Submissions for Software Contained in Medical Devices to support device software with a major level of concern.
Cybersecurity information provided in accordance with the 2014 FDA guidance document ● Content of Premarket Submissions for Management of Cybersecurity in Medical Devices.
Human factors testing in DEN170052 was used to support that device users could safely use the device.

J. Summary of Clinical Performance Testing

The purpose of this 510(k) is to add the option for the user to obtain the daily basal body temperature information used by the Natural Cycles fertility algorithm from the Oura ring, a wearable temperature monitor. There have been no changes to how the Natural Cycles algorithm determines the daily fertility status.

A clinical study was conducted to compare the daily temperatures generated by a wearable

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temperature monitor, the Oura ring, to a two decimal place oral thermometer for use by the NaturalCycles algorithm. The study included 40 women who were experienced users of both Natural Cycles and entering their daily temperature using an oral thermometer but did not have experience using the Oura ring with Natural Cycles. The mean age of the study participants was 31.3 ± 4.9 years, and the mean menstrual cycle length for complete cycles during the study was 28.6 ± 4.4 days. The majority (38) of the women were located in Sweden, with one each in the US and Switzerland.

The women wore the Oura ring nightly, with the user's temperature information automatically synced to the Oura Cloud each morning, and also recorded their temperature each morning as taken using a two-decimal place oral thermometer. Data were collected over a total of 223 menstrual cycles, 155 of which were considered complete cycles per the study definition. The participants were also asked to record the results of luteinizing hormone (LH) tests each cycle. At least one positive LH test was submitted in 87 of the complete study cycles.

The results of the clinical study demonstrated that when temperature was inputted from either the Oura ring or the two-decimal place oral thermometer, the Natural Cycles algorithm was able to identify that ovulation had occurred, which was confirmed in the study by comparison to the 87 positive LH test results. Compared to the two-decimal place oral thermometer, the Natural Cycles algorithm provides additional 1.6 green days (not fertile) in the luteal phase of the menstrual cycle when the input temperature was from the Oura ring, without increasing the risk of unintended pregnancy.

K. Conclusion

A comparison of intended use and technological characteristics combined with performance data demonstrates that Natural Cycles is as safe and effective as the predicate device and supports a determination of substantial equivalence. Natural Cycles meets the special controls outlined in 21 CFR 884.5370, Software application for contraception.

Regulation Number and Section

§ 884.5370 Software application for contraception.

(a)
Identification. A software application for contraception is a device that provides user-specific fertility information for preventing a pregnancy. This device includes an algorithm that performs analysis of patient-specific data (e.g., temperature, menstrual cycle dates) to distinguish between fertile and non-fertile days, then provides patient-specific recommendations related to contraception.(b)
Classification. Class II (special controls). The special controls for this device are:(1) Clinical performance testing must demonstrate the contraceptive effectiveness of the software in the intended use population.
(2) Human factors performance evaluation must be provided to demonstrate that the intended users can self-identify that they are in the intended use population and can correctly use the application, based solely on reading the directions for use for contraception.
(3) Software verification, validation, and hazard analysis must be performed. Documentation must include the following:
(i) A cybersecurity vulnerability and management process to assure software functionality; and
(ii) A description of the technical parameters of the software, including the algorithm used to determine fertility status and alerts for user inputs outside of expected ranges.
(4) Labeling must include:
(i) The following warnings and precautions:
(A) A statement that no contraceptive method is 100% effective.
(B) A statement that another form of contraception (or abstinence) must be used on days specified by the application.
(C) Statements of any factors that may affect the accuracy of the contraceptive information.
(D) A warning that the application cannot protect against sexually transmitted infections.
(ii) Hardware platform and operating system requirements.
(iii) Instructions identifying and explaining how to use the software application, including required user inputs and how to interpret the application outputs.
(iv) A summary of the clinical validation study and results, including effectiveness of the application as a stand-alone contraceptive and how this effectiveness compares to other forms of legally marketed contraceptives.