EmbryoGen® (1204) is a modification of EmbryoGen® (1203) (K120136), where the base medium has been changed from EmbryoAssist® (K080473) to the new ORIGIO Sequential Cleav™ (K133912) medium. EmbryoGen® (1204) contains GM-CSF (Granulocyte macrophage- colony stimulating factor), in the same concentration as EmbryoGen® (1203). EmbryoGen® (1204) is an aseptically filtered, colorless, non viscous solution, which is ready to use by professionals within assisted reproduction. EmbryoGen® (1204) is contained in 3 ml 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.

AI/ML Overview

The provided document is a 510(k) Summary for a medical device called EmbryoGen® (Cat. No. 1204). This device is a reproductive culture medium used for human embryos. The document focuses on demonstrating substantial equivalence to a predicate device, EmbryoGen® (Cat. No. 1203).

The 510(k) summary does not contain acceptance criteria or details of a study designed to prove the device meets specific performance acceptance criteria in the typical sense of a clinical trial for diagnostic or interventional devices with quantifiable outcomes like sensitivity, specificity, accuracy, etc.

Instead, the submission for EmbryoGen® (1204) relies on demonstrating substantial equivalence to a legally marketed predicate device (EmbryoGen® (1203)). This means the "acceptance criteria" are effectively the characteristics and performance of the predicate device. The "study" proving the device meets these criteria is a comparison of technological characteristics and performance data between the new device and the predicate device, as well as another cleared device (ORIGIO® Sequential Cleav™).

Here's an breakdown based on the provided text, addressing your questions where possible:

1. A table of acceptance criteria and the reported device performance

Since this is a submission for substantial equivalence of a culture medium, the "acceptance criteria" are the established specifications and comparable performance parameters of the predicate device and other similar cleared devices. The "reported device performance" are the specifications of the new device.

Acceptance Criteria (Predicate/Cleared Device Specs)	Reported Device Performance (EmbryoGen® (1204))
Indication for use: Culture of human embryos until 2-8 cell stage; embryo transfer day 2 or 3	Indication for use: Culture of human embryos until the 2-8 cell stage; embryo transfer at day 2 or 3. (Narrowed from predicate which included fertilization)
pH: 7.3-7.5 (EmbryoGen® (1203)); identical to ORIGIO® Sequential Cleav™	pH: 7.2-7.4 (A little lower than predicate, but identical to ORIGIO® Sequential Cleav™)
Osmolality (mOsm/kg): 272-288	Osmolality (mOsm/kg): 272-288
Endotoxin (EU/mL): <0.15	Endotoxin (EU/mL): <0.15
Aseptically filtered: X	Aseptically filtered: X
1-cell MEA: ≥80%	1-cell MEA: ≥80%
GM-CSF ELISA test: >80%	GM-CSF ELISA test: >80%
GM-CFS potency (TF-1 cell assay): 80-125%	GM-CFS potency (TF-1 cell assay): 80-125%
Protein source: HSA Protein Supplementation 2 mg/mL (EmbryoGen® (1203)); 5 mg/mL (ORIGIO® Sequential Cleav™)	Protein source: HSA Protein Supplementation 5 mg/mL
Drugs: Gentamicin sulphate 0.01 mg/mL	Drugs: Gentamicin sulphate 0.01 mg/mL
Recombinant human GM-CSF: 2 ng/mL	Recombinant human GM-CSF: 2 ng/mL
Base Medium: Similar components as ORIGIO® Sequential Cleav™ (e.g., 21 amino acids, Na Hyaluronate, no SSR)	Base Medium: Identical to ORIGIO® Sequential Cleav™ (e.g., 21 amino acids, Na Hyaluronate, no SSR)
Biocompatibility: Pass cytotoxicity, sensitization, irritation tests (ISO 10993-1:2009)	Biocompatibility: Passed cytotoxicity, sensitization, and irritation tests
Shelf life: 26 weeks for predicate	Shelf life: Validated to 26 weeks

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

The document does not specify a "test set" sample size for a typical clinical performance study. The "performance data" section primarily discusses laboratory tests and stability studies, which would involve samples of the culture medium itself, not biological samples from human patients in a clinical trial.

1-cell MEA (Mouse Embryo Assay): This is a biological assay using mouse embryos. The document states a performance criterion (≥80%) but does not specify the sample size (e.g., number of mouse embryos, number of batches tested) used to demonstrate this for EmbryoGen® (1204).
Stability studies: These tests involved multiple batches of the product over time. The sample size (number of batches) is not explicitly stated.
Data Provenance: Not specified as a clinical trial. The manufacturing company, ORIGIO a/s, is based in Denmark.

3. Number of experts used to establish the ground truth for the test set and the qualifications of those experts (e.g. radiologist with 10 years of experience)

This is not applicable to this type of device submission. There is no concept of "ground truth" established by human experts in the context of this culture medium's substantial equivalence demonstration. The "ground truth" is essentially the established specifications and safety profile of the predicate device and the general scientific understanding of IVF media components.

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

Not applicable. There is no clinical read by human readers that would require an adjudication method.

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 device is a culture medium, not an AI-powered diagnostic or decision support system that would involve human readers or AI assistance.

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

Not applicable. This device is a culture medium, not an algorithm.

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

The "ground truth" in this context is based on:

Established scientific understanding and regulatory requirements for reproductive media.
Performance specifications of the predicate device (EmbryoGen® (1203)) and another cleared device (ORIGIO® Sequential Cleav™).
Standardized laboratory tests for pH, osmolality, endotoxin, specific protein concentrations, and biological assays like MEA (Mouse Embryo Assay), GM-CSF ELISA, and GM-CSF potency (TF-1 cell assay).
Biocompatibility testing (cytotoxicity, sensitization, irritation) against ISO 10993-1:2009 standards.

There is no "expert consensus" or "pathology" in the sense of interpreting images or clinical findings.

8. The sample size for the training set

Not applicable. This device is a culture medium, not an AI/machine learning model that requires a training set.

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

Not applicable. As stated above, this device does not involve a training set.

Summary

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Image /page/0/Picture/2 description: The image shows a stylized logo or wordmark that reads "origio". The letters are designed with a somewhat retro or vintage aesthetic, featuring thick, rounded strokes. The "g" is uniquely styled with a comma-like shape below it, and the "i" is formed by two vertically stacked circles, giving the wordmark a distinctive and memorable appearance.

JUN 1 6 2014

K140317- EmbryoGen®

510(K) SUMMARY

Summary of Safety and Effectiveness Information Supporting a Substantially Equivalent Determination

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 Submitted: June 04, 2014
Device Identification
Trade name:	EmbryoGen® (Cat. No. 1204)
Common name:	EmbryoGen® (Cat. No. 1204)
Classification name:	Reproductive media and supplements (21 CFR 884.6180, ProductCode MQL)

Predicate devices:

EmbryoGen® (Cat. No. 1203) (K120136)

Description

EmbryoGen® (1204) is an aseptically filtered, colorless, non viscous solution, which is ready to use by professionals within assisted reproduction. EmbryoGen® (1204) is contained in 3 ml 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. )

Indication for use

EmbryoGen® is for culture of human embryos until the 2-8 cell stage. EmbryoGen® can also be used for embryo transfer at day 2 or 3.

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The indication for use for EmbryoGen® (1204) has been narrowed and does not include fertilization as EmbryoGen (1203). The indication for EmbryoGen® (1204) is considered comparable to the predicate since both media are for culture until 2-8 cell stage including human embryo transfer. Thus the reduction in indication does not represent a new intended use nor does it pose any safety or effectiveness issues.

Technological Characteristics

Table 1 compares the technological characteristics of EmbryoGen® (1204) to the predicate EmbryoGen® (1203). Both similarities and differences are illustrated.

Product	EmbryoGen® (1204)	EmbryoGen® (1203)
Indication for use	EmbryoGen® is for culture of human embryos until the 2-8 cell stage.EmbryoGen® can also be used for embryo transfer at day 2 or 3.	EmbryoGen® is for fertilization and culture until 2-8 cell stage.EmbryoGen® can also be used for embryo transfer at day 2 or 3.
Product specification
pH	7.2-7.4	7.3-7.5
Osmolality (mOsm/kg)	272-288	272-288
Endotoxin (EU/mL)	<0.15	<0.15
Aseptically filtered	X	X
1-cell MEA	≥80%	≥80%
GM-CSF ELISA test	>80%	>80%
GM-CFS potency (TF-1 cell assay)	80-125%	80-125%
Base Medium
Physiological salts	X	X
Bicarbonate	X	X
HEPES	-	X
Glucose, lactate, pyruvate	X	X
Amino Acids	21 amino acids	11 amino acids
EDTA	X	X
Vitamins	Ca-pantothenate, Folic acid	Mixture of 10 vitamins
Sodium Hyaluronate	X	-
Synthetic Serum Replacement (SSR)	-	X
Protein source
HSA Protein Supplementation	5 mg/mL	2 mg/mL
Drugs
Gentamicin sulphate	0.01 mg/mL	0.01 mg/mL
Insulin¹	-	0.51 µg/mL
Product	EmbryoGen® (1204)	EmbryoGen® (1203)
Recombinant human GM-CSF	2 ng/mL	2 ng/mL

Table 1. Comparison of EmbryoGen® (1204) and the predicate EmbryoGen® (1203).

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Insulin is a component in SSR

The technological characteristics of EmbryoGen® (1204) are comparable to those of the predicate device. The differences are all in the base medium which is identical to the cleared ORIGIO® Sequential Cleav™ (K1333912) with the same intended use as EmbryoGen (1204). The main differences between EmbryoGen (1204) and EmbryoGen (1203) are:

Synthetic Serum Replacement (SSR %: SSR has been removed in EmbryoGen (1204), . SSR is a metal ion buffer primarily containing a balanced mixture of trace elements and human recombinant insulin . The majority of the commercially available ART media do not contain SSR or similar components. Moreover, as EmbryoGen (1204) is identical in formulation to the cleared ORIGIO Sequential Cleav (K1333912) which also does not contain SSR, it does not represent a new technology.
EDTA: The concentration of EDTA is decreased compared to EmbryoGen® (1203) but is . identical to the EDTA concentration in ORIGIO® Sequential Cleav™(K1333912). A decreased EDTA concentration in EmbryoGen® (1204) therefore do not represent a new technology
Human Serum Albumin (HSA): EmbryoGen® (1204) contains 5 mg/mL HSA compared to 2 . mg/mL HSA in EmbryoGen® (1203). The majority of commercially available culture media with the same intended use including ORIGIO® Sequential Cleav™ (K1333912) contain 5 mg/mL HSA and thus, do not represent a new technology.
Amino Acids: EmbryoGen® (1204) contains 21 amino acids (both non-essential and . essential amino acids), whereas EmbryoGen® (1203) contains 11 non-essential amino acids only. EmbryoGen® (1204) are equivalent to the cleared ORIGIO® Sequential Cleav™(K1333912) in regards of the different amino acids as well as concentration and thus, do not represent a new technology.
Vitamins: EmbryoGen® (1204) contains the vitamins folic acid and calcium pantothenate in similar concentration range as predicate and other cleared ART media (ORIGIO® Sequential Cleav™ (K1333912)). Thus, folic acid and calcium pantothenate have a history of use in other ART media and do not represent a new technology
Sodium hyaluronate: EmbryoGen® (1204) contains sodium hyaluronate whereas . EmbryoGen 91203) does not. The concentration of sodium hyaluronate is 0.05 g/l which is in the range found in other commercial IVF media with the same intended use( ORIGIO® Sequential Cleav™ (K1333912)).

The technological characteristics of EmbryoGen® (1204) are comparable to the predicate device. do not impact substantial equivalence, and do not raise new types of safety or effectiveness questions.

Performance data

The product specifications for EmbryoGen® (1204) and EmbryoGen® (1203) are similar regarding sterility, endotoxin, osmolality, GM-CSF ELISA test, GM-CSF potency (TF-1 cell assay) and Mouse Embryo Assay (MEA) test.

Regarding the pH, the specification limit is a little lower for EmbryoGen® (1204) than EmbryGen® (1203). However, the specification for EmbryoGen® (1204) is identical to the pH specification for ORIGIO® Sequential Cleav™ (K1333912) with the identical indication for use for culture of human

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embryos until 2-8 cell stage and embryo transfer. Thus, the pH specification for EmbryoGen® (1204) does not raise any safety concerns.

The shelf life of EmbryoGen® has been validated in stability studies to 26 weeks. The parameters which have been tested in the stability studies through shelf life includes pH, osmolality, endotoxin, · HSA concentration, MEA, GM-CSF ELISA, GM-CSF potency (TF-1 Cell assay) and sterility.

In general, EmbryoGen® (1204) medium is subject to the same control methods and, to a significant degree, contain the same components as the predicate device EmbryoGen® (1203). EmbryoGen® (1204) has similar handling procedures and storage conditions. Therefore, EmbryoGen® (1204) is considered substantially equivalent to the predicate device EmbryoGen® (1203) (K133912).

Biocompatibility

EmbryoGen® (1204) is categorized as a medium in direct contact with embryos until 2-8 cell stage. Since EmbryoGen® (1204) can also be used for human embryo transfer, it is also in direct contact with the uterus (patient). Biocompatibility testing was conducted on EmbryoGen® per ISO 10993-1:2009 and included assessments of cytotoxicity, sensitization, and irritation. Results of these studies demonstrated that EmbryoGen® materials were biocompatible. EmbryoGen® (1204) is therefore considered safe for culture of human embryos as well as transfer of embryos to the patient (uterus).

Conclusion

The conclusion from the performance and safety data, intended use comparison, product formulation comparison and test specification comparison, demonstrates that EmbryoGen® (1204) is suitable for its intended use, and that the technological characteristics are substantially equivalent to the predicate device EmbryoGen® (1203) in which substantial equivalence has been demonstrated.

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Image /page/4/Picture/1 description: The image shows the logo for the U.S. Department of Health & Human Services. The logo consists of a stylized caduceus symbol, which is a staff with two snakes entwined around it. The symbol is surrounded by the text "DEPARTMENT OF HEALTH & HUMAN SERVICES - USA" in a circular arrangement. The text is written in all capital letters.

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

June 16, 2014

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

Re: K140317

Trade/Device Name: EmbryoGen® Regulation Number: 21 CFR§ 884.6180 Regulation Name: Reproductive media and supplements Regulatory Class: II Product Code: MQL Dated: March 17, 2014 Received: March 20, 2014

Dear Tove Kjær,

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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Page 2 - Tove Kjær

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-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,

Image /page/5/Picture/6 description: The image shows the name "Herbert P. Lerner -S" in a bold, sans-serif font. The name is written in black ink on a white background. The letters are evenly spaced and the name is easy to read. The letters "P. L" are surrounded by a faint, dotted circle.

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) K140317

Device Name EmbryoGen®

Indications for Use (Describe)

EmbryoGen® is for culture of human embryos until the 2-8 cell stage. EmbryoGen® can also be used for embryo transfer at day 2 or 3.

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)

PLEASE DO NOT WRITE BELOW THIS LINE - CONTINUE ON A SEPARATE PAGE IF NEEDED.

FOR FDA USE ONLY : Concurrence of Center for Devices and Radiological Health (CDRH) (Signature)

Herbert P. Lerner 2014.06.16 14:5

FORM FDA 3881 (9/13)

Form Approved: OMB No. 0910-0120 Expiration Date: December 31, 2013 See PRA Statement on last page.

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.