Replens is a personal lubricant for vaginal application, intended to moisturize and lubricate, to enhance the ease and comfort of intimate sexual activity and supplement the body's natural lubrication. This product is compatible with natural rubber latex condoms and synthetic (polyurethane and polyisoprene) condoms.

Device Description

Replens Vaginal Moisturizer is a non-sterile, water-based, white to off-white, non-irritating, non-greasy, non-staining vaginal gel delivered in single-use, pre-filled applicators as a long-lasting moisturizer for vaginal dryness. The use of prefilled applicators provides less mess in application. Replens Vaginal Moisturizer is intended for ongoing use, not exclusively for use during intimate sexual activity.

AI/ML Overview

The provided document is a 510(k) Summary for Replens Long-Lasting Vaginal Moisturizer (in pre-filled applicators). It primarily focuses on demonstrating substantial equivalence to a predicate device for regulatory clearance rather than establishing a new device's performance against explicit acceptance criteria in a typical clinical study format for novel devices.

Therefore, the requested information, particularly regarding specific acceptance criteria, comprehensive effect sizes, and detailed ground truth establishment methods for a standalone AI algorithm, is largely not applicable or not explicitly stated in this type of regulatory submission. The document outlines safety and performance data in relation to its intended use and comparison to a predicate device.

However, I can extract and infer some information based on what is provided:

1. Table of Acceptance Criteria and Reported Device Performance

As this is a 510(k) for a personal lubricant, the "acceptance criteria" are generally tied to demonstrating safety, intended use (moisturizing and lubrication), and compatibility with condoms, rather than a quantifiable performance metric (like accuracy or sensitivity) typically seen in AI or diagnostic devices. The acceptance is implied by successfully passing various tests.

Acceptance Criteria (Inferred from testing)	Reported Device Performance
Biocompatibility:	Passed:
Cytotoxicity	-
Acute Vaginal Irritation	-
Subacute Vaginal Irritation	-
Subacute Vaginal Irritation with Histological Examination	-
Acute Systemic Toxicity	-
Hypersensitivity	-
Acute Oral Toxicity	-
Acute Dermal Toxicity	-
Dermal Irritation	-
Eye Irritation	-
Clinical Efficacy/Safety:	Concluded safe and well-tolerated and provided relief of symptoms: (Based on multiple clinical studies; specific metrics not detailed as acceptance criteria)
Influence on vaginal pH	Studies observed influence on vaginal pH, but specific target range for "acceptance" is not defined.
Influence on vaginal mucosa	Studies observed influence on vaginal mucosa.
Relief of patient's symptoms (e.g., vaginal dryness)	Studies reported relief of patient's symptoms.
Vaginal dryness index	Studies utilized vaginal dryness index.
Stability (Shelf life)	Confirmed: One (1) year shelf life.
Preservative Effectiveness (against microbial growth)	Successfully passed: USP <51> Antimicrobial Effectiveness Test requirements.
Dosing Consistency (applicator delivers required amount)	Confirmed: Prefilled applicator delivers the required amount of gel.
Condom Compatibility (strength/integrity of latex/synthetic condoms)	Confirmed: Does not materially affect the strength or integrity of natural rubber latex or synthetic (polyurethane and polyisoprene) condoms.
Substantial Equivalence to Predicate Device (Intended Use, Formulation, Safety, Technological Characteristics)	Concluded as substantially equivalent.

2. Sample Sizes and Data Provenance for Test Set (Clinical Studies)

The "test set" in this context refers to the clinical studies used to support the safety and efficacy of the Replens device.

Whitehead (1991): 32 patients enrolled (Replens group)
Nachtigall (1994): 15 patients enrolled
Gelfand and Wendman (1994): 25 patients enrolled
Bachmann et al. (1991): 89 patients enrolled (Replens group)
Bachmann et al. (1992): 54 patients enrolled
Zinny and Lee (1991): 26 patients enrolled
Young et al. (1991): 30 patients enrolled
Nakamura (1991): 10 patients enrolled

Data Provenance: The document does not explicitly state the country of origin for each study. However, authors like Bachmann, Nachtigall, Gelfand, and Wendman are typically associated with studies conducted in North America (primarily the US). Retrospective or Prospective: The study designs (double-blind, cross-over, open, parallel) indicate these were prospective clinical trials.

3. Number of Experts and Qualifications for Ground Truth

This information is not provided in the summary. For a medical device like Replens, "ground truth" would be established through patient-reported outcomes, clinical assessments (e.g., pH measurements, vaginal dryness index assessment by a clinician), and potentially histological examination (as mentioned for subacute vaginal irritation). The specific number and qualifications of experts involved in these assessments are not detailed.

4. Adjudication Method for the Test Set

This information is not provided. Clinical studies typically have methods for assessing patient outcomes and safety events, but a specific "adjudication method" in the context of diagnostic agreement (like for imaging AI) is not relevant or described here.

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

No, an MRMC comparative effectiveness study was not performed as this device is a personal lubricant, not an AI diagnostic tool. The concept of "human readers improving with AI vs. without AI assistance" is not applicable here.

6. Standalone Performance Study

Yes, the clinical studies listed (Bachmann et al., Nachtigall, Gelfand and Wendman, Zinny and Lee, Young et al., Nakamura) represent standalone performance studies for the Replens device. They assess its effects, safety, and patient-reported outcomes without "human-in-the-loop" interaction in the sense of an AI algorithm enhancing human decision-making.

7. Type of Ground Truth Used

The ground truth used in the clinical studies for Replens appears to be a combination of:

Clinical Assessments: Vaginal pH determination, vaginal mucosa observations, vaginal dryness index.
Patient-Reported Outcomes: Relief of patient's symptoms (vaginal dryness), completion of diary cards.
Pathology: Histological examination (for subacute vaginal irritation testing).
Safety Data: Adverse event reporting and tolerability assessments.

8. Sample Size for the Training Set

This information is not applicable. Replens is a medical device (personal lubricant), not an AI algorithm. Therefore, there is no "training set" in the context of machine learning. The clinical studies mentioned serve as the evidence base for its safety and efficacy.

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

This information is not applicable as there is no training set for an AI algorithm.

Summary

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KIGIZHI

Replens Vaginal Moisturizer (Applicators)

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Idnr: 2.0 510k Summary Version: 2.2 Date: August 13, 2010 Page 1 of 4

510(k) Summary

AUG 1 7 2010

Submitter:

Lil' Drug Store Products, Inc. 1201 Continental Place NE Cedar Rapids, IA 52402

Contact Person:

Tricia Miller Director of Regulatory Telephone: 319-294-3745 Facsimile: 319-393-3494 Email: tmiller@lildrugstore.com

Date:

August 13, 2010

Proprietary Name:

Replens Long-Lasting Vaginal Moisturizer (in pre-filled applicators)

Common name:

Personal Lubricant

Classification name:

21 C.F.R. 884.5300 Lubricant, Patient, Vaginal, Latex Compatible Product Code: NUC Class: 2 Obstetrics/Gynecology Review Panel:

Predicate Device:

CVS Personal Lubricant & Moisturizer Device Name: 510(k) Number: K062682 NUC, MMS Product Code:

Intended Use:

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Replens Vaginal Moisturizer (Applicators) 5

Idnr: 2.0 510k Summary Version: 2.2 Date: August 13, 2010 Page 2 of 4

with natural rubber latex condoms and synthetic (polyurethane and polyisoprene) condoms.

Description of Device

Replens Vaginal Moisturizer contains ingredients commonly used in other products for vaginal use sold as medical devices and cosmetics. All ingredients are either NF, USP, or are considered "generally recognized as safe for their intended use". The quantitative formulation is proprietary and considered confidential commercial information.

Technological Characteristics of the Device

Replens Vaginal Moisturizer is substantially equivalent to the identified previously cleared vaginal lubricant predicate with respect to its design and materials, principle of operation, function, formulation, and intended use. It is also substantially equivalent to other water-based vaginal lubricants and personal lubricants being commercially marketed in the U.S.

Summary of Performance Data

Biocompatibility Testing: The following biocompatibility testing has been performed on Replens Long-Lasting Vaginal Moisturizer:

Cytotoxicity .
Acute Vaqinal Irritation .
Subacute Vaqinal Irritation .
Subacute Vaginal Irritation with Histological Examination .
. Acute Systemic Toxicity
. Hypersensitivity
. Acute Oral toxicity
Acute Dermal Toxicity .
Dermal Irritation .
. Eve Irritation.

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Replens Vaginal Moisturizer (Applicators) 5

Idnr: 2.0 510k Summary Version: 2.2 Date: August 13, 2010 Page 4 of 4

Citation	No.PatientsEnrolled(Replens)	StudyDesign*	Dosage Regimen	Duration
Whitehead	32	D-B, X-over	2.5 g, 3 x weekly plusoption of additionalapplication prior tointercourse.	8 weeks
Nachtigall	15	Open, parallel	2.5 g, 3 x weekly	3 months
Gelfand andWendman	25	Open	2.5 g, 3 x weekly, plusoption of additionalapplication prior tointercourse.	3 months

D-B = double-blind; X-over = cross-over design

The parameters employed in the studies included the influence of Replens on vaginal pH and the vaginal mucosa, the relief of the patient's symptoms, the vaginal dryness index, determination of vaginal pH at varying time intervals after single or multiple applications of the gel, PAP smears and the completion of diary cards by the patient. All of the studies concluded that Replens was safe and well-tolerated.

Stability Data: Stability data confirms a shelf life of one (1) year for Replens Long-Lasting Vaginal Moisturizer.

Preservative Effectiveness: Replens Long-Lasting Vaginal Moisturizer has successfully passed the requirements of the USP <51> Antimicrobial Effectiveness Test.

Dosing Consistency Study: Dosing consistency studies confirm the prefilled applicator delivers the required amount of gel.

Condom Compatibility Testing: Condom compatibility testing confirms that Replens Long-Lasting Vaginal Moisturizer does not materially affect the strength or integrity of natural rubber latex or synthetic condoms (polyurethane and polyisoprene).

Conclusion

Based on the information presented in the 510(k) notice, it is concluded that Replens Long-Lasting Vaginal Moisturizer (in pre-filled applicators) for OTC use is safe and effective for its proposed indications and is substantially equivalent in intended use, formulation, safety, and technological characteristics to the identified predicate device and other similar waterbased personal lubricants.

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Replens Vaginal Moisturizer (Applicators) 510k

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Idnr: 2.0 510k Summary Version: 2.2 Date: August 13, 2010 Page 3 of 4

Page 414

Clinical Studies: The following clinical studies have been performed on Replens Long-Lasting Vaginal Moisturizer:

Bachmann GA, Notelovitz M, Gonzalez SJ, Thompson C, Morecraft BA. . (1991) Vaginal Dryness in Menopausal Women: Clinical Characteristics and Nonhormonal Treatment. Clinical Practice in Sexuality, 7(9): 1-8.
Bachmann GA, Notelovitz M, Kelly SJ, Owens A, Thompson C. (1992) . Long Term Nonhormonal Treatment of Vaginal Dryness. Clinical Practice in Sexuality, 8(8/9): 3-8.
Zinny MA, Lee S. (1991) Double-Blind Study of the Comparative . Effects of Two Gels on Vaginal pH in Postmenopausal Women. Today's Therapeutic Trends, 8(4): 65-72.
Younq R, Goldzieher J, Kaufman R. (1991) A Study of the Effects of . Col-1003 In Postmenopausal Women. Unpublished.
Nakamura R. (1991) Evaluation of Col-1003 in the treatment of . vaginal dryness in postmenopausal women. Unpublished.
Whitehead M. (1991) A Randomised Double Blind Evaluation of Col-. 1003, a bioadhesive polymer system vaginal moisturizing gel and, KY Brand Lubricating Jelly in the treatment of vaginal dryness in postmenopausal women receiving concomitant oral hormone replacement therapy. Unpublished
Nachtigall LE. (1994) Comparative study: Replens versus local . estrogen in menopausal women. Fertility and Sterility, 61(1): 178-180.
Gelfand MM, Wendman E. (1994) Treating Vaginal Dryness in Breast . Cancer Patients: Results of Applying a Polycarbophil Moisturizing Gel. J. Women's Health, 3(6): 427-433.

The format of the studies listed above is summarized in the table below:

Citation	No.PatientsEnrolled(Replens)	StudyDesign*	Dosage Regimen	Duration
Bachmann et al	89	D-B, X-over	2.5 g per day	5 days
Bachmann et al	54	Open	2.5 g, 3 x weekly	12 months
Zinny and Lee	26	D-B, parallel	2.5 g alternate nights	4 weeks
Young et al	30	Open	2.5 g, 3 x weekly, plusoption of additionalapplication prior tointercourse.	12 months
Nakamura	10	Open, X-overbetweentreatmentdurations	2.5 g daily	1-5 days

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

Lil Drug Store Products, Inc. c/o Mr. Mark A. Job Responsible Third Party Regulatory Technology Services, Inc. 1394 25th Street, NW BUFFALO MN 55313

AUG 1 7 2010

·Re: K101241

· Trade/Device Name: Replens Long-Lasting Vaginal Moisturizer Gel (in pre-filled applicators)

Regulation Number: 21 CFR $884.5300.

Regulation Name: Condom Regulatory Class: II

Product Code: NUC Dated: July 30, 2010

Received: August 2, 2010

Dear Mr. Job:

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.

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

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Page 2

adverse events) (21 CFR 803); good manufacturing practice requirements as set forth in the quality systems (QS) 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 go to http://www.fda.gov/AboutFDA/CentersOffices/CDRH/CDRHOffices/ucm115809.htm for the Center for Devices and Radiological Health's (CDRH's) Office of Compliance. Also, please note the regulation entitled, "Misbranding by reference to premarket notification" (21CFR 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 Small Manufacturers, International and Consumer Assistance at its toll-free number (800) 638-2041 or (301) 796-7100 or at its Internet address

http://www.fda.gov/MedicalDevices/Resourcesfor You/Industry/default.htm.

Sincerely yours,

Huker Lemur us

Herbert P. Lerner, M.D., Director (Acting) Division of Reproductive. Gastro-Renal and Urological Devices Office of Device Evaluation Center for Devices and Radiological Health

Enclosure

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Replens Vaginal Moisturizer (Applicators) 5

Idnr: 1.0 Indications Statement Version: 2.1 Date: May 25, 2010 Page 1 of 1

STATEMENT OF INDICATIONS FOR USE

510(k) Number: KIO1241

Device Name: Replens Long-Lasting Vaginal Moisturizer (in prefilled applicators)

Indications for Use: Replens is a personal lubricant for vaginal application, intended to moisturize and lubricate, to enhance the ease and comfort of intimate sexual activity and supplement the body's natural lubrication. This product is compatible with natural rubber latex condoms and synthetic (polyurethane and polyisoprene) condoms.
Prescription Use (Per 21 CFR 801.109) OR

Over-the-Counter Use × (Optional Format 1-2-96)

(PLEASE DO NOT WRITE BELOW THIS LINE - CONTINUE ON ANOTHER PAGE IF NEEDED) Concurrence of CDRH, Office of Device Evaluation (ODE)

Shay L. Wa

(Division Sign-Off) Division of Reproductive, Abdominal, and Radiological Devices 510(k) Number

Regulation Number and Section

§ 884.5300 Condom.

(a)
Identification. A condom is a sheath which completely covers the penis with a closely fitting membrane. The condom is used for contraceptive and for prophylactic purposes (preventing transmission of sexually transmitted infections). The device may also be used to collect semen to aid in the diagnosis of infertility.(b)
Classification. (1) Class II (special controls) for condoms made of materials other than natural rubber latex, including natural membrane (skin) or synthetic.(2) Class II (special controls) for natural rubber latex condoms. The guidance document entitled “Class II Special Controls Guidance Document: Labeling for Natural Rubber Latex Condoms Classified Under 21 CFR 884.5300” will serve as the special control. See § 884.1(e) for the availability of this guidance document.