(90 days)
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).
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 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 (NC° Birth Control), Conception (NC° Plan Pregnancy), and Pregnancy (NC° Follow Pregnancy). For NC° Birth Control 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, previous submissions cleared the Oura Ring and Apple Watch for automatic temperature input to the Natural Cycles algorithm. 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 pregnant when compared to women who have not been on hormonal birth control within the 12 months prior to using the device. This 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. The subject of this submission is the proposed inclusion of a Predetermined Change Control Plan (PCCP) that enables use of a broader range of temperature measuring devices for future wearable integrations with the Natural Cycles application. There are no changes to the Natural Cycles application from the application cleared in K231274.
The document describes the acceptance criteria and the results of a study for the Natural Cycles software application, which is intended for contraception and conception planning. This submission (K241006) primarily focuses on the inclusion of a Predetermined Change Control Plan (PCCP) to allow for the future integration of various temperature measuring devices, rather than changes to the core Natural Cycles application itself. The performance testing described is in the context of validating a new wearable temperature measuring device against the established performance of the Natural Cycles algorithm with existing temperature input methods (e.g., manual oral thermometer).
Here's a breakdown of the requested information:
1. Table of Acceptance Criteria and Reported Device Performance:
| KPI (Key Performance Indicator) | Acceptance Criteria (Specification) | Reported Device Performance (Implied by conclusion of substantial equivalence) |
|---|---|---|
| Std (Day-to-day variability) | CI upper bound ≤ 0.234 | Met |
| Ratio | CI lower bound ≥ 2.04 | Met |
| Ovulation detection | CI lower bound ≥ 85.5% | Met |
| Ovulation resolution | CI lower bound ≥ 76.1% | Met |
| PPA (Positive Percent Agreement) | CI lower bound ≥ 96.5% | Met |
| Fraction of green days | No more than 2 additional red days per cycle compared to the oral thermometer | Met |
Note: The document states "The information outlined above demonstrates that Natural Cycles is as safe and effective as the predicate device," implying that the device (or rather, the combination of the Natural Cycles algorithm with any new wearable validated under the PCCP) meets these acceptance criteria.
2. Sample size used for the test set and the data provenance:
The document does not explicitly state the sample size used for the test set or the data provenance (e.g., country of origin, retrospective/prospective). It refers to the KPIs in the context of validating new wearables. The study described is for evaluating the performance of the Natural Cycles algorithm when using temperatures from a device under consideration (i.e., a new wearable) as input.
3. Number of experts used to establish the ground truth for the test set and the qualifications of those experts:
The document does not specify the number or qualifications of experts used to establish ground truth for the test set.
4. Adjudication method (e.g. 2+1, 3+1, none) for the test set:
The document does not specify any adjudication method for the test set.
5. If a multi-reader multi-case (MRMC) comparative effectiveness study was done, what was the effect size of how much human readers improve with AI vs without AI assistance:
This is a standalone software application for contraception/conception planning, primarily based on an algorithm processing temperature data. The concept of "human readers" or "AI assistance" in the context of medical image interpretation (which is where MRMC studies are common) is not applicable here. Therefore, no MRMC comparative effectiveness study was done, and there is no effect size for human readers improving with AI assistance.
6. If a standalone (i.e. algorithm only without human-in-the-loop performance) was done:
Yes, the performance criteria (KPIs) listed are for the standalone algorithm's performance when analyzing temperature data, specifically within the context of a "device under consideration" (referring to a new wearable providing temperature input). The "Positive Percent Agreement (PPA)" refers to the algorithm's safety in predicting fertile windows without human intervention in the interpretation of the output days.
7. The type of ground truth used (expert consensus, pathology, outcomes data, etc.):
The ground truth appears to be established by comparing the algorithm's performance against biological markers and established menstrual cycle physiology, especially in relation to ovulation detection. For instance:
- "Detected ovulations – the fraction of cycles with positive LH where ovulation is detected by the Natural Cycles algorithm..." (LH refers to Luteinizing Hormone, a biological marker for ovulation).
- "Ovulation resolution – fraction of cycles with positive LH and ovulation detected, where ovulation is detected within two days from the LH-only ovulation day."
- The "Fraction of green days" and comparison to an "oral thermometer" suggest a benchmark against a standard measurement method and expected physiological outcomes.
8. The sample size for the training set:
The document does not specify the sample size for the training set.
9. How the ground truth for the training set was established:
The document does not explicitly describe how the ground truth for the training set was established. However, given the nature of the device, it can be inferred that the training would likely involve historical physiological data, including daily temperature readings, menstruation cycle information, and potentially LH/pregnancy test results, correlated with actual ovulation and fertility outcomes.
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July 11, 2024
NaturalCycles Nordic AB Megan Callanan Senior Regulatory and Compliance Specialist St Eriksgatan 63B Stockholm, 112 34 SWEDEN
K241006 Re:
Trade/Device Name: Natural Cycles Regulation Number: 21 CFR 884.5370 Regulation Name: Software Application for Contraception Regulatory Class: II Product Code: PYT Dated: April 19, 2024 Received: April 19, 2024
Dear Megan Callanan:
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.
The FDA's substantial equivalence determination also included the review and clearance of your Predetermined Change Control Plan (PCCP), "Predetermined Change Control Plan for New Wearables", version number 4.2. Under section 515(b)(1) of the Act, a new premarket notification is not required for a
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change to a device cleared under section 510(k) of the Act, if such change is consistent with an established PCCP granted pursuant to section 515C(b)(2) of the Act. Under 21 CFR 807.81(a)(3), a new premarket notification is required if there is a major change or modification in the intended use of a device, or if there is a change or modification in a device that could significantly affect the safety or effectiveness of the device, e.g., a significant change or modification in design, material, chemical composition, energy source, or manufacturing process. Accordingly, if deviations from the established PCCP result in a major change or modification in the intended use of the device, or result in a change or modification in the device that could significantly affect the safety or effectiveness of the device, then a new premarket notification would be required consistent with section 515C(b)(1) of the Act and 21 CFR 807.81(a)(3). Failure to submit such a premarket submission would constitute adulteration and misbranding under sections 501(f)(1)(B) and 502(0) of the Act, respectively.
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 (OS) regulation (21 CFR Part 820) for devices or current good manufacturing practices (21 CFR Part 4, Subpart A) for combination products; and, if applicable, the electronic product radiation control provisions (Sections 531-542 of the Act); 21 CFR Parts 1000-1050.
Also, please note the regulation entitled, "Misbranding by reference to premarket notification" (21 CFR 807.97). For questions regarding the reporting of adverse events under the MDR regulation (21 CFR Part 803), please go to https://www.fda.gov/medical-device-safety/medical-device-reportingmdr-how-report-medical-device-problems.
For comprehensive regulatory information about mediation-emitting products, including information about labeling regulations, please see Device Advice (https://www.fda.gov/medicaldevices/device-advice-comprehensive-regulatory-assistance) and CDRH Learn (https://www.fda.gov/training-and-continuing-education/cdrh-learn). Additionally, you may contact the Division of Industry and Consumer Education (DICE) to ask a question about a specific regulatory topic. See
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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) K241006
Device Name Natural Cycles
Indications for Use (Describe)
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).
| Type of Use (Select one or both, as applicable) | |
|---|---|
| ------------------------------------------------- | -- |
Prescription Use (Part 21 CFR 801 Subpart D)
Over-The-Counter Use (21 CFR 801 Subpart C)
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510(k) Summary K241006 — Natural Cycles
| Submitter: | NaturalCycles Nordic ABSt Eriksgatan 63b112 34 Stockholm, Sweden |
|---|---|
| SubmitterContact: | Name: Megan CallananPhone: (216)744-4524Email: Megan.callanan@naturalcycles.com |
| Date Prepared: | June 25, 2024 |
| Device Name and Classification Information | |
| Trade Name: | Natural Cycles |
| Common Name: | Software application for contraception |
| RegulationName: | Software application for contraception |
| RegulationNumber: | 21 CFR 884.5370 |
| Regulatory Class: | II |
| Product Code: | PYT (Device, fertility diagnostic, contraceptive, software application) |
| Predicate Device | |
| K231274 Natural CyclesThe predicate device has not been subject to a design-related recall. | |
| Device Description | |
| Natural Cycles is an over-the-counter web and mobile-based standalonesoftware application that monitors a woman's menstrual cycle usinginformation entered by the user and informs the user about her past,current and future fertility status. The following information is used by theNatural Cycles software:• daily 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 |
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status. Natural Cycles is available in three modes: Contraception (NC° Birth Control), Conception (NC° Plan Pregnancy), and Pregnancy (NC° Follow Pregnancy). For NC° Birth Control 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, previous submissions cleared the Oura Ring and Apple Watch for automatic temperature input to the Natural Cycles algorithm. 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 pregnant when compared to women who have not been on hormonal birth control within the 12 months prior to using the device. This 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. The subject of this submission is the proposed inclusion of a Predetermined Change Control Plan (PCCP) that enables use of a broader range of temperature measuring devices for future wearable integrations with the Natural Cycles application. There are no changes to the Natural Cycles application from the application cleared in K231274. Indications for Use Natural Cvcles 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).
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| Comparison with Predicate Device | ||||
|---|---|---|---|---|
| A detailed comparison of the intended use and technological features ofthe subject and predicate device are described in the table below: | ||||
| Parameter | Subject DeviceNatural CyclesK241006 | Predicate DeviceNatural CyclesK231274 | Comparison | |
| Indications forUse statement | Natural Cycles is astand-alone softwareapplication, intendedfor women 18 yearsand older, to monitortheir fertility.Natural Cycles can beused for preventing apregnancy(contraception) orplanning a pregnancy(conception). | Natural Cycles is astand-alone softwareapplication, intendedfor women 18 yearsand older, to monitortheir fertility.Natural Cycles can beused for preventing apregnancy(contraception) orplanning a pregnancy(conception). | Same | |
| Use Environment | App is downloaded touser's smartphoneand used in the homeenvironment | App is downloaded touser's smartphoneand used in the homeenvironment | Same | |
| InputInformation | Manual input oftwo-decimal dailybasal bodytemperature(BBT)measurements orautomatic inputfrom a validatedthird partytemperaturemeasuring device. Manual input ofinformation aboutthe user'smenstruationcycle, i.e., startdate, number ofdays. Optional manualinput of ovulationor pregnancy testresults. | Manual input oftwo-decimal dailybasal bodytemperature(BBT)measurements orautomatic inputfrom a validatedthird partytemperaturemeasuring device. Manual input ofinformation aboutthe user'smenstruationcycle, i.e., startdate, number ofdays. Optional manualinput of ovulationor pregnancy testresults. | Same | |
| OutputInformation | NC Birth Controlmode: For each | NC Birth Controlmode: For each | Same | |
| day, whether thewoman is fertile(red), or non-fertile (green),with descriptivetexts.• NC PlanPregnancy mode:Fertility statusresults aredisplayed as ascale for fertiledays, and greenfor non-fertiledays, togetherwith descriptivetexts.• NC FollowPregnancy mode:Provideseducationalinformation aboutthe progress ofthe pregnancy.• All users in NCBirth Controlmode or NC PlanPregnancy modereceive theovulation date forthe month anddaily statement offertility status.Historic data isavailable for allusers. | day, whether thewoman is fertile(red), or non-fertile (green),with descriptivetexts.• NC PlanPregnancy mode:Fertility statusresults aredisplayed as ascale for fertiledays, and greenfor non-fertiledays, togetherwith descriptivetexts.• NC FollowPregnancy mode:Provideseducationalinformation aboutthe progress ofthe pregnancy.• All users in NCBirth Controlmode or NC PlanPregnancy modereceive theovulation date forthe month anddaily statement offertility status.Historic data isavailable for allusers. | |||
| As outlined in the table above, the subject and predicate device haveidentical indications for use statements and have the same intendeduse. The subject and predicate device have identical technologicalcharacteristics. In addition, the subject device includes a PCCP tovalidate future wearables to be used with the Natural Cycles application.The inclusion of the PCCP in the subject devices does not raise differentquestions of safety and effectiveness. |
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Traditional 510(k) K241006 - Natural Cycles
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| Summary of Non-Clinical and/orClinicalPerformanceTesting | A PCCP was submitted to obtain authorization from FDA to add morewearables providing temperature as an input to the Natural Cyclesfertility algorithm in the future without requiring additional 510(k)s. | |
|---|---|---|
| Key Performance Indicators (KPIs): | ||
| Positive Percent Agreement (PPA) to assess product safety and contraceptive effectiveness, i.e., how often the user is exposed to a pregnancy risk because of a wrongly flagged green day in the fertile window. Fraction of green days assigned by the fertility algorithm over the total number of days for a given cycle, then averaged over all cycles. Day to day variability (std) – the standard deviation of the daily temperature values. Ratio between the temperature phase separation and the standard deviation, i.e., the temperature difference between the pre-ovulatory and post-ovulatory phases of the menstrual cycles. Detected ovulations – the fraction of cycles with positive LH where ovulation is detected by the Natural Cycles algorithm using the temperatures from the device under consideration as input. Ovulation resolution – fraction of cycles with positive LH and ovulation detected, where ovulation is detected within two days from the LH-only ovulation day. | ||
| Specifications: | ||
| KPI | Specification | |
| Std | CI upper bound ≤ 0.234 | |
| Ratio | CI lower bound ≥ 2.04 | |
| Ovulation detection | CI lower bound ≥ 85.5% | |
| Ovulation resolution | CI lower bound ≥ 76.1% | |
| PPA | CI lower bound ≥ 96.5% | |
| Fraction of green days | No more than 2 additional red days percycle compared to the oral thermometer | |
| Conclusion | ||
| The information outlined above demonstrates that Natural Cycles is as | The information outlined above demonstrates that Natural Cycles is as safe and effective as the predicate device and supports a determinationof substantial equivalence. |
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§ 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.