ORIGIO® Sperm Wash is intended for washing of spermatozoa, the isolation of motile viable sperm by swim-up method, dilution of ORIGIO gradients, and holding sperm for IUI procedure

ORIGIO® Gradient™ 100, ORIGIO® Gradient™ 90 and ORIGIO® Gradient™ 40/80 are for separation of motile sperm from the ejaculate by the density gradient method.

Device Description

ORIGIO® Sperm Wash and ORIGIO® Gradient™ devices are for separation of motile sperm from semen and handling of sperm. These devices are based on the same formulation, but differ in the content of Human Serum Albumin (HSA), NaCl, bicarbonate, and silane silica. The silane silica generates the density, thus it is an ingredient in the ORIGIO® Gradient™ devices only and is not present in ORIGIO® Sperm Wash. All subject devices, except ORIGIO® Gradient™ 100, contain gentamicin and HSA.

The subject devices are aseptically filtered, colorless solutions. ORIGIO® Gradient™ devices are viscous while ORIGIO® Sperm Wash is non-viscous. They are contained in transparent polyethylene terephthalate glycol (PETG) bottles with high density polyethylene (HDPE) closures, available in card board boxes, individually labeled and with instruction for use provided as a package insert.

AI/ML Overview

The document provided describes the acceptance criteria and performance data for ORIGIO® Sperm Wash and ORIGIO® Gradient™ devices (100, 90, and 40/80). However, it does not describe a study involving an AI device or human readers with AI assistance. The document pertains to reproductive media and supplements, which are chemical solutions used in assisted reproductive technologies, not complex imaging or diagnostic AI systems.

Therefore, many of the requested points, such as AI-related metrics (human readers with/without AI assistance, standalone AI performance), expert qualifications, and adjudication methods, are not applicable to this submission.

Here's the information that can be extracted from the provided text, focused on the device's characteristics and its comparison to predicate devices:

1. Table of Acceptance Criteria and Reported Device Performance

Criteria	Acceptance Criteria (ORIGIO® Sperm Wash)	Acceptance Criteria (ORIGIO® Gradient™ 40)	Acceptance Criteria (ORIGIO® Gradient™ 80)	Acceptance Criteria (ORIGIO® Gradient™ 90)	Acceptance Criteria (ORIGIO® Gradient™ 100)	Reported Device Performance
pH	7.95-8.495	Not specified directly for each gradient, but overall "commonly seen in reproductive media"	Not specified directly for each gradient, but overall "commonly seen in reproductive media"	Not specified directly for each gradient, but overall "commonly seen in reproductive media"	Not specified directly for each gradient, but overall "commonly seen in reproductive media"	"met all product specifications" (for all devices)
Osmolality (mOsm/kg)	272-288	317-333	297-313	Not specified	Not specified	"met all product specifications" (for all devices)
Density (g/ml)	N/A	1.048-1.062	1.098-1.112	1.105-1.119	1.123-1.137	"met all product specifications" (for all devices)
Human Sperm Survival Test	≥80% of control	Not specified directly for gradients	Not specified directly for gradients	Not specified directly for gradients	Not specified directly for gradients	"met all product specifications" (for all devices)
Endotoxin (EU/ml)	≤0.15	≤0.8	≤0.8	≤0.8	≤0.8	"met all product specifications" (for all devices)
Sterility	No growth (SAL 10⁻³)	No growth (SAL 10⁻³)	No growth (SAL 10⁻³)	No growth (SAL 10⁻³)	No growth (SAL 10⁻³)	"met all product specifications" (for all devices)
HSA concentration (mg/ml)	10	5	5	5	N/A	"met all product specifications" (for all devices)

Note: The document states that "The bench testing demonstrated that the subject devices met all product specifications," but it doesn't provide specific numerical results for each criterion to show how they met them, only the acceptance ranges.

2. Sample size used for the test set and the data provenance (e.g., country of origin of the data, retrospective or prospective)

Test set sample size: Not explicitly stated in terms of a "test set" as would be used for an AI algorithm. The performance evaluation was conducted on "sperm separated using subject devices" for "motility, morphology, viability, purity and integrity." The number of samples/donors used for this evaluation is not provided.
Data provenance: Not specified. The document indicates the devices are manufactured by ORIGIO a/s in Denmark, but the location of the performance testing is not mentioned. The nature of the studies appears to be laboratory bench testing rather than clinical trials with patient data.

3. Number of experts used to establish the ground truth for the test set and the qualifications of those experts

Not applicable. This relates to the evaluation of a medical device (reproductive media), not an algorithmic diagnostic or imaging tool that requires human expert interpretation for ground truth establishment. The performance evaluation involved laboratory tests on sperm characteristics.

4. Adjudication method (e.g., 2+1, 3+1, none) for the test set

Not applicable. No adjudication method described as it's not a study involving human interpretation of data for ground truth.

5. If a multi reader multi case (MRMC) comparative effectiveness study was done, If so, what was the effect size of how much human readers improve with AI vs without AI assistance

Not applicable. This is not an AI device or an imaging/diagnostic device that would involve human readers.

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

Not applicable. This is not an AI device. The "standalone performance" refers to the device's ability to perform its function (sperm washing and separation) independently, which was evaluated through bench testing. The document states "The bench testing demonstrated that the subject devices met all product specifications." and "The sperm separated using subject devices were evaluated for motility, morphology, viability, purity and integrity in comparison with predicate and other cleared devices."

7. The type of ground truth used (expert consensus, pathology, outcomes data, etc.)

The "ground truth" for the device's performance relies on laboratory measurements and established biological criteria for sperm characteristics (motility, morphology, viability, purity, integrity) as well as chemical and physical properties of the media (pH, osmolality, density, endotoxin levels, sterility, HSA concentration). There isn't a "ground truth" in the diagnostic sense (like a pathology report for an image).

8. The sample size for the training set

Not applicable. This is not an AI device, so there is no training set in the context of machine learning.

9. How the ground truth for the training set was established

Not applicable. As above, no training set for an AI model.

Summary

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

July 22, 2016

ORIGIO a/s Tove Kjaer Director Corporate Requlatory Affairs Knardrupvej 2 2760 Måløv Denmark

Re: K153267

Trade/Device Name: ORIGIO® Sperm Wash, ORIGIO® Gradient™ 100, ORIGIO® Gradient™ 90 and ORIGIO® Gradient™ 40/80 Regulation Number: 21 CFR& 884.6180 Regulation Name: Reproductive media and supplements Regulatory Class: II Product Code: MQL Dated: June 21, 2016 Received: June 23, 2016

Dear Tove Kjaer,

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.

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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); 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/ResourcesforYou/Industry/default.htm.

Sincerely yours.

Joyce M. Whang -S

for

Benjamin R. Fisher, Ph.D. Director Division of Reproductive, Gastro-Renal, and Urological Devices Office of Device Evaluation Center for Devices and Radiological Health

Enclosure

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Indications for Use

Form Approved: OMB No. 0910-0120 Expiration Date: January 31, 2017 See PRA Statement below.

510(k) Number (if known)

Device Name

ORIGIO® Sperm Wash, ORIGIO® Gradient™ 100, ORIGIO® Gradient™ 90 and ORIGIO® Gradient™ 40/80

Indications for Use (Describe)

ORIGIO® Sperm Wash is intended for washing of spermatozoa, the isolation of motile viable sperm by swim-up method, dilution of ORIGIO gradients, and holding sperm for IUI procedure

ORIGIO® Gradient™ 100, ORIGIO® Gradient™ 90 and ORIGIO® Gradient™ 40/80 are for separation of motile sperm from the ejaculate by the density gradient method.

	☒ Prescription Use (Part 21 CFR 801 Subpart D)
	☐ Over-The-Counter Use (21 CFR 801 Subpart C)

CONTINUE ON A SEPARATE PAGE IF NEEDED.

This section applies only to requirements of the Paperwork Reduction Act of 1995.

DO NOT SEND YOUR COMPLETED FORM TO THE PRA STAFF EMAIL ADDRESS BELOW.

The burden time for this collection of information is estimated to average 79 hours per response, including the
time to review instructions, search existing data sources, gather and maintain the data needed and complete
and review the collection of information. Send comments regarding this burden estimate or any other aspect
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"An agency may not conduct or sponsor, and a person is not required to respond to, a collection of information unless it displays a currently valid OMB number."

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

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510(k) SUMMARY

510(k) Number:	K153267
Submitted by:	ORIGIO a/sKnardrupvej 22760 MåløvDenmark
Contact person:	Tove KjærDirector Corporate Regulatory AffairsORIGIO a/sPhone: +45 4679 0220Fax: +45 4679 0300

Date Prepared: July 21, 2016

Device Identification:

Trade name:	ORIGIO® GradientTM 100 (Cat. No. 8400)ORIGIO® GradientTM 90 (Cat, No. 8401)ORIGIO® GradientTM 40/80 (Cat, No. 8402)ORIGIO® Sperm Wash (Cat, No. 8405)
Common name:	Density Gradient and Sperm Wash
Classification name:	Reproductive media and supplements (21 CFR 884.6180, ProductCode MQL)

Predicate Devices:

SupraSperm™ System (K003404) from ORIGIO is the predicate device for ORIGIO® Gradient™ devices

Sperm Preparation Medium (K991332) from ORIGIO is the predicate device for ORIGIO® Sperm Wash.

Device Description:

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Criteria	ORIGIO® SpermWash	ORIGIO® Gradient™
		40	80	90	100
pH	7.95-8.495
Osmolality (mOsm/kg)	272-288	317-333	297-313
Density (g/ml)	N/A	1.048-1.062	1.098-1.112	1.105-1.119	1.123-1.137
Human Sperm Survival Test	≥80% of control
Endotoxin (EU/ml)	≤0.15	≤0.8
Sterility	No growth (SAL10-3)
HSA concentration (mg/ml)	10	5	5	5	N/A

Indications for Use:

ORIGIO®Sperm Wash is intended for washing of spermatozoa, the isolation of motile viable sperm by swim-up method, dilution of ORIGIO® gradients, and holding sperm for IUI procedure.

ORIGIO®Gradient™ 100, ORIGIO® Gradient™ 90 and ORIGIO® Gradient™ 40/80 are for the separation of motile sperm from the ejaculate by the density gradient method.

Performance and Safety Data:

Product Specifications

The bench testing demonstrated that the subject devices met all product specifications.

Biocompatibility

Since ORIGIO® Sperm Wash can also be used for IUI (Intrauterine insemination), it mav have direct contact with the uterus (patient). In accordance with ISO 10993-1:2009, the cytotoxicity, sensitization and irritation tests have been conducted on this device and the results demonstrate that ORIGIO® Sperm Wash is safe.

Sterilization Validation

The subject devices are manufactured by aseptically filtration that was validated in accordance with EN/ISO 13408-2:2011. These products have a sterility assurance level (SAL) of 10-3.

Shelf-Life

The shelf-life study covering all product specifications has been conducted on the subject devices. The results demonstrate that Gradient™ 100 has a 20-week shelf-life whereas the other subject devices have a 36-week shelf-life in unopened bottle under recommended storage conditions. In addition, all subject devices are stable for four weeks under recommended storage conditions after the bottles have been opened.

Effectiveness of Separation of Motile Sperm

The sperm separated using subject devices were evaluated for motility, morphology. viability, purity and integrity in comparison with predicate and other cleared devices. The results demonstrate that the subject and predicate devices have comparable performance.

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Predicate Device Comparison:

ORIGIO® Sperm Wash

ORIGIO® Sperm Wash and its predicate device have the same intended use. The subject device is different from predicate devices in pH; however, this difference is commonly seen in reproductive media. Regarding formulation, there are following differences between the subject and predicate devices:

. Citrate is present in ORIGIO® Sperm Wash at higher concentration compared to the predicate device. However, citrate is a natural component in semen and present in much higher concentration than in ORIGIO® Sperm Wash.
. Sodium bicarbonate is present in ORIGIO® Sperm Wash at lower concentration compared to the predicate device, but within the range of other cleared sperm wash media.
. Unlike the predicate device, Synthetic Serum Replacement (SSR) is not present in ORIGIO® Sperm Wash. However, SSR is also absent in other cleared media intended for sperm handling. Therefore, absence of SSR is not considered detrimental for the sperm cells.
. HSA concentration has been increased from 5 mg/ml in the predicate device to 10 mg/ml in ORIGIO® Sperm Wash. However, the level of HSA in ORIGIO® Sperm Wash is still much lower than physiological level.
Taurine is present in ORIGIO® Sperm Wash but absent in the predicate device. ● However, taurine which is widely used in ART media, including cleared devices with similar indication.

Taken together, the differences do not raise new types of questions. Performance data shows that ORIGIO® Sperm Wash is as safe and effective as the predicate device. Therefore, ORIGIO® Sperm Wash is substantially equivalent to the predicate device in terms of safety and effectiveness.

ORIGIO® Gradient™ devices

ORIGIO® Gradient™ devices and their predicate device have the same intended use. Gradient™ devices are different from the predicate device in pH and osmolality; however, these differences are commonly seen in reproductive media. Regarding formulation, there are following differences between the subject and predicate devices:

ORIGIO® Gradient™ 40 contains a slightly higher concentration of NaCl, as ● compared to the predicate device, in order to adjust the medium to a slightly higher osmolality. However, the NaCl concentration used is still within the physiological range of semen.
Taurine is present in ORIGIO® Gradient™ devices but absent in the predicate . device. However, taurine is widely used in ART media, including cleared devices with similar indication.
HSA concentration has been increased to 5 mg/ml in ORIGIO® Gradient™ 40, 80 ● and 90. This concentration is within the normal range of cleared media intended for sperm.

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Citrate is present in ORIGIO® Gradient™ devices at higher concentration . compared to the predicate device. However, citrate is a natural component in semen and present in much higher concentration than in ORIGIO® Gradient™ devices.
. ORIGIO® Gradient™ devices do not contain SSR or phenol red compared to the predicate device. However, absence of SSR and phenol red are commonly seen in cleared media intended for sperm and therefore, it is not considered detrimental for the sperm cells.

Taken together, the differences do not raise new types of questions. Performance data shows that ORIGIO® Gradient™ devices are as safe and effective as the predicate device. Therefore, ORIGIO® Gradient™ devices are substantially equivalent to the predicate device in terms of safety and effectiveness.

Regulation Number and Section

§ 884.6180 Reproductive media and supplements.

(a)
Identification. Reproductive media and supplement are products that are used for assisted reproduction procedures. Media include liquid and powder versions of various substances that come in direct physical contact with human gametes or embryos (including water, acid solutions used to treat gametes or embryos, rinsing solutions, sperm separation media, supplements, or oil used to cover the media) for the purposes of preparation, maintenance, transfer or storage. Supplements are specific reagents added to media to enhance specific properties of the media (e.g., proteins, sera, antibiotics, etc.).(b)
Classification. Class II (special controls) (mouse embryo assay information, endotoxin testing, sterilization validation, design specifications, labeling requirements, biocompatibility testing, and clinical testing). The device, when it is phosphate-buffered saline used for washing, and short-term handling and manipulation of gametes and embryos; culture oil used as an overlay for culture media containing gametes and embryos; and water for assisted reproduction applications, is exempt from the premarket notification procedures in subpart E of part 807 of this chapter subject to the limitations in § 884.9.