The product is intended for in vitro culture of human embryos following fertilization until Day 5/6 of development. The media can also be used for embryo transfer.

Device Description

SAGE 1-Step™ GM-CSF with HSA and SAGE 1-Step™ GM-CSF with SPS are assisted reproduction embryo culture media products consisting agents, physiological salts, energy substrates, amino acids, antibiotics, protein supplements (HSA or SPS), and granulocyte-macrophage colony-stimulating factor (GM-CSF, 2 ng/ml). These devices are aseptically filtered (sterility assurance level of 10 %), and supplied in 3 ml glass vials. They are tested for pH, osmolality, embryotoxicity, endotoxin, sterility, and GM-CSF concentration and potency before lot release. These devices have a shelf-life of 16 weeks, and can be used for up to seven days after vial opening when stored at 2-8°C.

AI/ML Overview

Here's an analysis of the acceptance criteria and study information based on the provided text, focused on the SAGE 1-Step™ GM-CSF with HSA and SAGE 1-Step™ GM-CSF with SPS devices:

This document is a 510(k) summary for a medical device that appears to be an embryo culture media, not an AI/ML powered device, therefore some of the requested information (like multi-reader multi-case studies, AI impact, human-in-the-loop, training set sizes, and expert qualifications for ground truth in the context of diagnostic performance) are not applicable. The evaluations are primarily focused on the chemical, physical, and biological properties of the media itself.

Acceptance Criteria and Reported Device Performance

Acceptance Criteria (Specification)	Reported Device Performance (SAGE 1-Step™ GM-CSF)
pH: 7.2-7.4	pH: 7.2-7.4
Osmolality: 257-273 mOsm/kg	Osmolality: 257-273 mOsm/kg
MEA (Mouse Embryo Assay): ≥80% blastocysts at 96h (1-Cell MEA)	MEA: ≥80% blastocysts at 96h (1-Cell MEA)
Endotoxin: <0.15 EU/ml	Endotoxin: <0.15 EU/ml (LAL)
Sterility: Aseptic Filtration SAL 10⁻³, no microbial growth	Sterility: Aseptic Filtration SAL 10⁻³, no growth (per USP <71>)
GM-CSF concentration: 80-120% recovery	GM-CSF concentration: 80-120% recovery (by ELISA)
GM-CSF potency: 80-125% potency	GM-CSF potency: 80-125% potency (TF-1 cell assay)
Shelf-Life (at specified tests)	16 weeks

Study Information

Sample Size used for the test set and the data provenance:
- Sample Size: The document does not specify a numerical sample size for individual tests like pH, osmolality, endotoxin, sterility, or GM-CSF concentration/potency beyond "real-time" shelf-life testing. For the Mouse Embryo Assay (MEA), it states "One-cell mouse embryos were exposed...", but the exact number of embryos or replicates is not provided.
- Data Provenance: The studies were performed as part of the regulatory submission by ORIGIO a/s (Denmark). The data is generated from non-clinical laboratory testing (in vitro), not human patient data. It is inherently "prospective" in the sense that the tests were conducted specifically for this submission on the manufactured media.
Number of experts used to establish the ground truth for the test set and the qualifications of those experts:
- This question is not applicable as the device is not an AI/ML diagnostic or image analysis tool. Ground truth in this context refers to established laboratory standards and measurement techniques (e.g., pH meters, osmometers, ELISA, cell assays, microscopic assessment of embryo development against a standard). The "ground truth" is determined by the output of these standardized assays, not by expert consensus on complex diagnostic cases.
Adjudication method (e.g., 2+1, 3+1, none) for the test set:
- This is not applicable for this type of device and study. Adjudication methods like 2+1 are typically used for reconciling disagreements among human readers/annotators in diagnostic studies. The results here are based on objective laboratory measurements.
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:
- No, a MRMC comparative effectiveness study was not done. This type of study is relevant for diagnostic devices that involve human interpretation, often assisted by AI. This device is an embryo culture media, not a diagnostic tool requiring human reader interpretation in its intended use.
If a standalone (i.e. algorithm only without human-in-the-loop performance) was done:
- This is not applicable. There is no algorithm or AI component in this medical product. The performance is the inherent biological and chemical properties of the media itself.
The type of ground truth used (expert consensus, pathology, outcomes data, etc.):
- The "ground truth" for the performance specifications relies on established laboratory methodologies and reference standards:
  - Standardized Analytical Measurements: pH meters, osmometers, spectrophotometers (for ELISA), LAL assays for endotoxin.
  - Biological Assays: Mouse Embryo Assay (MEA) results (percentage of embryos reaching blastocyst stage), TF-1 cell assay for GM-CSF potency. These assays have predefined criteria for success and are considered objective measures of the media's biological suitability.
  - Sterility Testing: USP <71> standards for microbial growth.
The sample size for the training set:
- This is not applicable as this device is not an AI/ML product. There is no "training set" in the context of machine learning. The media's formulation is developed based on scientific understanding of embryo biology.
How the ground truth for the training set was established:
- This is not applicable as there is no training set for an AI/ML algorithm. The "ground truth" for the media's development and validation would stem from scientific literature on embryo development, established laboratory protocols, and regulatory standards for reproductive media.

Summary

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Image /page/0/Picture/0 description: The image contains the logo of the U.S. Food and Drug Administration (FDA). On the left is the Department of Health & Human Services logo. To the right of that is the FDA logo, which is a blue square with the letters "FDA" in white. To the right of the blue square is the text "U.S. FOOD & DRUG ADMINISTRATION" in blue.

October 13, 2017

ORIGIO a/s Tove Kjaer Director, Corporate Regulatory Affairs Knardrupvej 2 Malov, 2760 Denmark

Re: K172197 Trade/Device Name: SAGE 1-Step™ GM-CSF with HSA, SAGE 1-Step™ GM-CSF with SPS Regulation Number: 21 CFR 884.6180 Regulation Name: Reproductive media and supplements Regulatory Class: Class II Product Code: MOL Dated: July 24, 2017 Received: July 26, 2017

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. 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);

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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 contact the Division of Industry and Consumer Education (DICE) 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. 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 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 Industry and Consumer Education (DICE) 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.

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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DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration

Indications for Use

510(k) Number (if known) K172197

Device Name

SAGE 1-Step™ GM-CSF with HSA SAGE 1-Step™ GM-CSF with SPS

Indications for Use (Describe)

The product is intended for in vitro culture of human embryos following fertilization until Day 5/6 of development. The media can also be used for embryo transfer

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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a CooperSurgical Company

K172197 Page 1 of 4

510(k) SUMMARY K172197

Submitter Information L
Submitter:

ORIGIO a/s Knardrupvej 2, 2760 Måløv, Denmark

Contact person:

Tove Kjær Director Corporate Regulatory Affairs ORIGIO a/s Phone: +45 4679 0220 Fax: +45 4679 0300 Email: tkjaer@origio.com

II. Date prepared: Oct. 13 2017

III. Device Information

Device Name:	SAGE 1-Step™ GM-CSF with HSASAGE 1-Step™ GM-CSF with SPS
Common name:	Embryo Culture Media
Classification name:	Reproductive media and supplements
Classification Number:	21 CFR 884.6180
Product Code:	MQL (Media, Reproductive)
Regulatory Class:	II

IV. Predicate Device

ORIGIO a/s - SAGE 1-Step™ with HSA and SAGE 1-Step™ with SPS (K133707)

These predicate devices have not been subject to any design-related recalls.

V. Indication for use

The product is intended for in vitro culture of human embryos following fertilization until Day 5/6 of development. The media can also be used for embryo transfer.

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VI. Device Description

These devices are aseptically filtered (sterility assurance level of 10 %), and supplied in 3 ml glass vials. They are tested for pH, osmolality, embryotoxicity, endotoxin, sterility, and GM-CSF concentration and potency before lot release. These devices have a shelf-life of 16 weeks, and can be used for up to seven days after vial opening when stored at 2-8°C.

VII. Comparison of Intended Use and Technological Characteristics of Subject and Predicate Devices

Parameter	Subject device-SAGE 1-StepTMGM-CSF (with HASor SPS) (K172197)	Predicate Device-SAGE 1-StepTM (withHAS or SPS)(K133707)	Comparison
Indications for Use	The product isintended for in vitroculture of humanembryos followingfertilization until Day5/6 of development.The media can alsobe used for embryotransfer.	This product isintended for in vitrofertilization andculture of humangametes andembryos fromfertilization until Day5/6 of development.The medium canalso be used forembryo transfer.	Different- Thesubject andpredicate devicesare both indicatedfor culturing embryosfollowing fertilizationuntil the blastocyststage (Day 5/6) ofdevelopment, andfor use in embryotransfer procedures.The predicate is alsoindicated for useduring fertilization,which is differentthan the subjectdevice. Thisdifference does notrepresent a newintended use, butrather a more limiteduse of the subjectdevice.
Formulation	Buffering agents,physiological salts	Buffering agents,physiological salts	Different -Baseformulations of the

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	energy substrates,amino acids,antibiotics, proteinsupplements (HSAor SPS), and GM-CSF	energy substrates,amino acids,antibiotics, andproteinssupplements (HSAor SPS)	subject andpredicate devicesare similar; however,the subject devicealso includes GM-CSF. Thisdifference does notraise differentquestions of safetyand effectiveness(e.g.,biocompatibility,embryotoxicity, etc.).
pH	7.2-7.4	7.2-7.4	Same
Osmolality	257-273	257-273	Same
MEA	1-Cell MEA: ≥80%blastocysts at 96h	1-Cell MEA: ≥80%blastocysts at 96h	Same
Endotoxin (EU/ml)	<0.15	<0.15	Same
Sterility	Aeptic FilterationSAL 10⁻³, no growth	Aeptic FilterationSAL 10⁻³, no growth	Same
Shelf-Life	16 weeks	26 weeks	Different - Theshelf-life of thesubject andpredicate devicesare different. Thisdifference does notraise differentquestions of safetyand effectiveness.

As noted in the table above, the devices have the same intended use and are technologically comparable. Differences in technological characteristics noted above do not raise different questions of safety or effectiveness.

VIII. Summary of Non-Clinical Performance Testing

The following studies have been performed to support substantial equivalence to the predicate devices:

pH 7.2-7.4 ●
. Osmolality - 257-273 mOsm/kg
Aseptic processing validation testing that meet the requirements in ISO 13408-2-2003

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Sterility testing per USP <71> No microbial growth ●
. Endotoxin testing per USP <85> - <0.15 EU/ml (LAL)
Mouse embryo assay (MEA) 1-Cell MEA: ≥80% blastocysts at 96h ●

One-cell mouse embryos were exposed to subject devices and cultured at 37°C in an atmosphere containing 5% CO2. The percent of embryos developed to the blastocyst stage at 96 hours were assessed in comparison with the control group.

GM-CSF concentration (by ELISA) 80-120% recovery .
GM-CSF potency (TF-1 cell assay) - 80-125% potency
Shelf-life testing (real-time) was conducted to ensure that the following product specifications are met at time zero and the end of shelf-life.
- pH O
- Osmolality O
- 1-Cell MEA O
- Endotoxin o
- Sterility O
- GM-CSF concentration O
- o GM-CSF potency

IX. Conclusion

The results of the performance testing conducted on the subject devices demonstrates that they are as safe and effective as the predicate devices and support substantial equivalence.

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.