BlastGen™ is based on ORIGIO® Sequential Blast™ (K133387) with the supplement of Leukine (Sargramostim) granulocyte macrophage colony-stimulating factor (GM-CSF).

BlastGen™ is a colorless, non-viscous solution contained in 3mL transparent glass bottles with white polypropylene caps, available in a single piece card board box, individually labeled and with instruction for use provided as a package insert. BlastGen™ is a ready to use by professionals for assisted reproduction.

BlastGen™ is quality control tested before release for pH, sterility, Mouse Embryo Assay, endotoxin, osmolality, GM-CSF concentration (by ELISA), GM-CSF potency (TF-1 cell assay) and human serum albumin (HSA) concentration (by ELISA).

AI/ML Overview

Here's an analysis of the acceptance criteria and study data for the BlastGen™ device, based on the provided text:

1. Table of Acceptance Criteria and Reported Device Performance

The FDA 510(k) summary does not explicitly state formal "acceptance criteria" in a tabular format for direct comparison with reported device performance. Instead, it presents various performance and safety data points that demonstrate equivalence to a predicate device. The implicit acceptance criterion for a 510(k) is "substantial equivalence" to a legally marketed predicate device.

However, based on the non-clinical and clinical evidence provided, we can infer some performance aspects that were evaluated.

Performance Characteristic	Implicit Acceptance Criterion (vs. Predicate/Control)	Reported Device Performance (BlastGen™)
Biocompatibility	Demonstrate safety (Non-cytotoxic, non-sensitizing, non-irritating)	"results demonstrated that BlastGen™ was safe."
Sterility	Achieve sterility assurance level (SAL) of 10⁻³	"SAL of 10⁻³."
Shelf-Life (Unopened)	Maintain product specifications (pH, osmolality, sterility, MEA, endotoxin, GM-CSF conc., GM-CSF potency, HSA conc.)	"26-week shelf-life" (Under recommended storage conditions)
Shelf-Life (Opened)	Maintain product specifications (pH, osmolality, sterility, MEA, endotoxin, GM-CSF conc., GM-CSF potency, HSA conc.)	"7-day stability" (After bottle opened)
Blastocyst Rate	Comparable to or improved over control/predicate (G1/G2)	"trend towards higher blastocyst rate" (vs. G1/G2, not statistically significant in one study)
Pregnancy Rate	Comparable to or improved over control/predicate	"trend towards higher pregnancy...rates" (vs. G1/G2 in one study)
Ongoing Implantation Rate	Comparable to or improved over control/predicate	"trend towards higher...ongoing implantation rates" (vs. G1/G2 in one study)
Embryo Development to Blastocyst	Increased proportion relative to control	"increased the proportion of embryos that developed to the blastocyst stage from 30 to 76%."
Developmental Competence (Hatching/Attachment)	Improved relative to control	"improved by GM-CSF"
Apoptotic Nuclei in Blastocysts	Reduced relative to control	"50% fewer apoptotic nuclei" (in 2 ng/ml GM-CSF vs. control)
Viable Inner Cell Mass Cells	Increased relative to control	"30% more viable inner cell mass cells" (in 2 ng/ml GM-CSF vs. control)

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

The primary clinical evidence mentioned is:

Sample Size: "a prospective randomized sibling zygote pilot study (n=371 zygotes)"
Data Provenance: Not explicitly stated (e.g., country of origin). The study is described as "prospective randomized sibling zygote pilot study." The names of authors (Nakajyo, Sjöblom) suggest international research, but the specific source country of the embryos/patients is not mentioned in this document.

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

This document describes a device (reproductive media) for culturing embryos, not a diagnostic device that requires expert-established ground truth for performance evaluation in the same way an imaging AI would. The "ground truth" for embryology outcomes (e.g., blastocyst formation, pregnancy) is typically based on biological observation and clinical outcomes. Therefore, the concept of "experts establishing ground truth for a test set" with specific qualifications (like radiologists) does not apply directly here. The "truth" is the biological outcome observed by embryologists/clinicians.

4. Adjudication Method for the Test Set

Not applicable in the context of this type of device and study. The outcomes (e.g., blastocyst formation, pregnancy) are objective biological assessments rather than subjective interpretations requiring adjudication.

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

No, a Multi-Reader Multi-Case (MRMC) comparative effectiveness study was not done.
This type of study is relevant for diagnostic devices where human readers interpret images or data, and the comparison is between human interpretation alone versus human interpretation with AI assistance. BlastGen™ is a culture medium, not a diagnostic imaging AI tool.

6. Standalone (Algorithm Only Without Human-in-the-Loop Performance) Study

No, a standalone "algorithm only" study was not done because BlastGen™ is a culture medium, not an algorithm or AI. Its performance is evaluated through biological outcomes in a laboratory and clinical setting, which inherently involves human embryologists and clinicians interacting with the embryos and patients.

7. Type of Ground Truth Used

The ground truth used for evaluating BlastGen's performance is biological and clinical outcomes, specifically:

Embryo development: Blastocyst formation rate, proportion of embryos reaching the blastocyst stage.
Embryo quality indicators: Apoptotic nuclei count, viable inner cell mass cell count.
Clinical outcomes: Pregnancy rate, ongoing implantation rates.
Pre-clinical tests: Mouse Embryo Assay (MEA), pH, osmolality, sterility, endotoxin, GM-CSF concentration, GM-CSF potency, and HSA concentration.

8. Sample Size for the Training Set

This information is not provided. The provided studies are performance evaluations of the final product, not related to the training of an algorithm.

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

This question is not applicable as BlastGen™ is a culture medium and not an algorithmic/AI device that requires a "training set" with established ground truth in the AI sense. Its formulation and development would be based on scientific research and biological principles, rather than machine learning training.

Summary

{0}------------------------------------------------

Image /page/0/Picture/1 description: The image shows the logo for the U.S. Department of Health & Human Services. The logo consists of a circular border with the text "DEPARTMENT OF HEALTH & HUMAN SERVICES - USA" arranged around the top half of the circle. Inside the circle is an emblem featuring a stylized depiction of three human profiles facing right, with flowing lines suggesting movement or connection.

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

February 29, 2016

Origio A/S Tove Kjaer Director Corporate Regulatory Affairs Knardrupvej 2 2760 Måløv Denmark

Re: K152932

Trade/Device Name: BlastGen™ Regulation Number: 21 CFR 884.6180 Regulation Name: Reproductive media and supplements Regulatory Class: Class II Product Code: MOL Dated: January 29, 2016 Received: February 8, 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. 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 (reporting of medical device

{1}------------------------------------------------

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 contact the Division of Industry and Consumer Education 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 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,

Image /page/1/Picture/8 description: The image shows the name "Herbert P. Lerner -S" in a large, sans-serif font. The text is black and appears to be the main subject of the image. In the background, there is a faint watermark or logo, possibly indicating the source or context of the image. The overall impression is a clear and simple presentation of the name.

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

{2}------------------------------------------------

Indications for Use

510(k) Number (if known) K152932

Device Name BlastGen™

Indications for Use (Describe)

BlastGen™ is for the culture of embryos from the 4-8 cell stage through to the blastocyst stage. BlastGen™ 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)

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 of this information collection, including suggestions for reducing this burden, to:

Department of Health and Human Services Food and Drug Administration Office of Chief Information Officer Paperwork Reduction Act (PRA) Staff PRAStaff@fda.hhs.gov

"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."

{3}------------------------------------------------

Image /page/3/Picture/1 description: The image shows the word "origio" in a stylized, sans-serif font. The color of the text is a deep purple. The letters are rounded and have a modern, minimalist design. The letter "g" is particularly unique, with a curved shape that resembles a number 8.

K152932 - BlastGen™

510(k) SUMMARY

Submitted by:	ORIGIO a/sKnardrupvej 2,2760 Måløv,Denmark
Contact Person:	Tove KjærDirector Corporate Regulatory AffairsORIGIO a/s
	Phone: +45 4679 0220Fax: +45 4679 0300
	Date Prepared:

Device Identification

Trade name:	BlastGen™ (Cat. No. 1205)
Common name:	BlastGen™ (Cat. No. 1205)
Classification name:	Reproductive media and supplements (21 CFR 884.6180, ProductCode MQL)

Predicate Devices: ORIGIO® Sequential Blast™ (Cat. No. 8305) (K133387)

Device Description:

BlastGen™ is based on ORIGIO® Sequential Blast™ (K133387) with the supplement of Leukine (Sargramostim) granulocyte macrophage colony-stimulating factor (GM-CSF).

Indication for Use:

BlastGen™ is for the culture of embryos from the 4-8 cell stage through to the blastocyst stage. BlastGen™ can also be used for embryo transfer.

Performance and Safety Data:

Biocompatibility

BlastGen™ is categorized as a medium in direct contact with embryos from the 4-8 cell stage to blastocyst stage. Since BlastGen™ can also be used for embryo transfer, it is also in contact with the uterus (patient). In accordance with ISO 10993-1:2009, the

{4}------------------------------------------------

cytotoxicity, sensitization and irritation tests have been conducted and the results demonstrated that BlastGen™ was safe.

Sterilization Validation

BlastGen™ is manufactured by aseptically filtration that was validated in accordance with EN/ISO 13408-2:2011. This product has a sterility assurance level (SAL) of 103.

Shelf-Life

The BlastGen™ has been evaluated for pH, osmolality, sterility, mouse embryo assay, endotoxin, GM-CSF concentration, GM-CSF potency and HSA concentration in shelf-life testing. Under recommended storage conditions. BlastGen™ has 26-week shelf-life in unopened bottle and 7-day stability after the bottle has been opened.

Clinical Evidence

A prospective randomized sibling zygote pilot study (n=371 zygotes) of GM-CSFcontaining media (EmbryoGen/BlastGen) for culturing embryos to the blastocyst stage showed a trend towards higher blastocyst rate in the EmbryoGen/BlastGen group compared to G1/G2 although these differences did not reach statistical significance. A trend towards higher pregnancy and ongoing implantation rates were also observed for EmbryoGen/BlastGen (Nakajyo et al., 2016).

The addition of GM-CSF increased the proportion of embryos that developed to the blastocyst stage from 30 to 76%. The developmental competence of these blastocysts (hatching and attachment to extracellular matrix-coated culture dishes), was also improved by GM-CSF (Sjöblom et al., 1999).

Blastocysts cultured in 2 ng/ml GM-CSF contained 50% fewer apoptotic nuclei and 30% more viable inner cell mass cells, compared to the control (Sjöblom et al., 2002)

Conclusion:

BlastGen™ and predicate device have the same indications and comparable technological characteristics. Based on non-clinical and clinical performance data, BlastGen™ is 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.