(133 days)
These products are intended for the in vitro fertilization and culture of human gametes and embryos from fertilization until Day 5/6 of development. The media can also be used for transfer.
The SAGE 1-Step 11 medium is intended for in vitro fertilization and culture of human gametes and embryos from fertilization until Day 5/6 of development. The medium can also be used for transfer. Two versions of the SAGE 1-Step™ medium are available: Catalogue no. 6701: SAGE 1-Step™ supplemented with Human Serum Albumin. Catalogue no. 6702: SAGE 1-Step™ supplemented with Serum Protein Supplement. Both versions of SAGE 1-Step™ are aseptically filtered, light pink, non viscous solutions, which are ready to use by professionals within assisted reproduction. The SAGE 1-Step™ media products are contained in 10 ml or 60 ml transparent Polyethylene Terephthalate Glvcol (PETG) bottles with high density polyethylene (HDPE) cap, available in a card boxes of 1 x 10 ml and 1 x 60 ml bottles. The bottles are individually labeled. The boxes also contain instruction for use provided as package insert.
The provided document describes the SAGE 1-Step™ culture medium for in vitro fertilization and embryo culture, comparing it to a predicate device, Global® Total®. The focus of the document is on establishing substantial equivalence to the predicate device, not on presenting a standalone study or a comparative effectiveness study with human readers and AI. Therefore, I can only address aspects related to the product specifications and how they compare to acceptance criteria, which are derived from the predicate device's performance.
Here's an analysis based on the available information:
1. Table of Acceptance Criteria and Reported Device Performance
The document does not explicitly define "acceptance criteria" for clinical performance, but rather compares the SAGE 1-Step™ to a predicate device's specifications. The implicit acceptance criterion for SAGE 1-Step™ is that its performance and specifications should be "comparable" or "similar" to the predicate, or that any differences do not raise new safety or effectiveness concerns.
| Performance Characteristic | Acceptance Criteria (from Predicate Global® Total®) | Reported SAGE 1-Step™ Performance (REF 6701 & 6702) | Outcome |
|---|---|---|---|
| pH | 7.2-7.4 | 7.2-7.4 | Meets |
| Osmolality (mOsm/kg) | 260-270 | 257-273 | Meets (slight wider range but considered acceptable) |
| Endotoxin (EU/mL) | <0.50 | <0.15 | Meets (improved) |
| Sterility | Negative | No growth | Meets |
| 1-cell MEA | >80% | ≥80% | Meets |
2. Sample Size Used for the Test Set and Data Provenance
The document does not specify a "test set" in the context of a clinical performance study using patient data. The performance data presented are primarily based on product specifications and laboratory tests (like Mouse Embryo Assay - MEA). Therefore, information regarding sample size used for a test set, its country of origin, or whether it was retrospective or prospective, is not provided.
3. Number of Experts Used to Establish Ground Truth for the Test Set and Qualifications of Those Experts
This information is not applicable as there is no human-involved "test set" or clinical study described where ground truth would need to be established by experts.
4. Adjudication Method for the Test Set
This information is not applicable as there is no human-involved "test set" or clinical study described that would require an adjudication method.
5. If a Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study Was Done, and Effect Size
No, a multi-reader multi-case (MRMC) comparative effectiveness study was not done. The document describes the technical comparison of a culture medium with a predicate device, not the comparison of human readers with and without AI assistance.
6. If a Standalone Study (Algorithm Only Without Human-in-the-Loop Performance) Was Done
No, a standalone study in the context of an algorithm's performance was not done. This document concerns a medical device (culture medium), not a diagnostic algorithm or AI. The product specifications mentioned (pH, osmolality, endotoxin, sterility, MEA) can be considered a type of "standalone" performance assessment for the medium itself, but not in the context of an AI algorithm.
7. The Type of Ground Truth Used
For the product specifications (pH, osmolality, endotoxin, sterility, 1-cell MEA), the "ground truth" is established through laboratory testing and validated analytical methods as per industry standards and regulatory requirements. For the Mouse Embryo Assay (MEA), the typical ground truth involves observing successful embryo development (e.g., to blastocyst stage) in a controlled environment, indicating the medium's suitability for supporting growth.
8. The Sample Size for the Training Set
There is no training set in the context of an AI algorithm described in this document. The development of SAGE 1-Step™ is based on established scientific principles of embryo culture and comparison with existing, cleared devices.
9. How the Ground Truth for the Training Set Was Established
This is not applicable as there is no training set for an AI algorithm. The "ground truth" for the development and validation of the SAGE 1-Step™ medium itself would be based on fundamental biological and chemical principles, experimental data from studies on embryo culture, and the historical performance data of the predicate device and other similar media.
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a CooperSurgical Company
K133707 Page 1 of 4
APR 1 6 2014
K-133707 -- SAGE 1-Step™
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: April 10, 2014 | |
| Device IdentificationTrade name: | SAGE 1-Step™ supplemented with Human Serum Albumin |
| SAGE 1-Step™ supplemented with Serum Protein Supplement | |
| Common name: | SAGE 1-Step™ |
| Classification name: | Reproductive media and supplements (21 CFR 884.6180, ProductCode MQL) |
| Predicate device:LifeGlobal: | LifeGlobal Global® Total® (K112083). |
Description
The SAGE 1-Step 11 medium is intended for in vitro fertilization and culture of human gametes and embryos from fertilization until Day 5/6 of development. The medium can also be used for transfer.
Two versions of the SAGE 1-Step™ medium are available:
- Catalogue no. 6701: SAGE 1-Step™ supplemented with Human Serum Albumin .
- Catalogue no. 6702: SAGE 1-Step™ supplemented with Serum Protein Supplement .
Both versions of SAGE 1-Step™ are aseptically filtered, light pink, non viscous solutions, which are ready to use by professionals within assisted reproduction.
The SAGE 1-Step™ media products are contained in 10 ml or 60 ml transparent Polyethylene Terephthalate Glvcol (PETG) bottles with high density polyethylene (HDPE) cap, available in a card boxes of 1 x 10 ml and 1 x 60 ml bottles. The bottles are individually labeled. The boxes also contain instruction for use provided as package insert.
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Compositions:
The different types of components included in SAGE 1-Step™ supplemented with Human Serum Albumin and SAGE™ 1 step supplemented with Serum Protein Supplement are provided in table 1.
Indication for use
This product is intended for in vitro fertilization and culture of human gametes and embryos from fertilization until Day 5/6 of development. The medium can also be used for embryo transfer.
Technological Characteristics
The design of the SAGE 1-Step™ as well as the predicate listed in this submission, are based on the concept to offer the embryos various components at any time, from fertilization until blastocyst stage. Table 1 compares the technological characteristics of SAGE 1-Step™ with the predicate Global® Total®. Both similarities and differences are illustrated.
SAGE 1-Step™ is for fertilization: culture and embryo transfer. Global® Total @ is intended for culture of human embryos from zygote to blastocyst and embryo transfer. In vivo the gametes and zyqote are exposed to the same environment as the spermatozoa fertilizes the oocyte and forms the zyqote in the part of the fallopian tube called the ampulla. Thus, the intended use for the SAGE 1-StepTM is considered comparable to the predicate and the differences are not considered to represent a new intended use nor does it pose any safety or effectiveness issues.
| Product | SAGE 1-Step™(REF 6701) | SAGE 1-Step™(REF 6702) | Global® Total® |
|---|---|---|---|
| Intended use | This product isintended for the in vitrofertilization and cultureof human gametesand embryos fromfertilization until Day5/6 of development.The medium can alsobe used for embryotransfer. | This product isintended for the in vitrofertilization and cultureof human gametesand embryos fromfertilization until Day5/6 of development.The medium can alsobe used for embryotransfer. | Culture of humanembryos from zygoteto blastocyst, andembryo transfer. |
| Product specification | |||
| pH | 7.2-7.4 | 7.2-7.4 | 7.2-7.4 |
| Osmolality (mOsm/kg) | 257-273 | 257-273 | 260-270 |
| Endotoxin (EU/mL) | <0.15 | <0.15 | <0.50 |
| Sterility | No growth | No growth | negative |
| 1-cell MEA | ≥80% | ≥80% | >80% |
| Formulation | |||
| Physiological salts | Magnesium SulphatePotassium ChloridePotassium PhosphateSodium Chloride | Magnesium SulphatePotassium ChloridePotassium PhosphateSodium Chloride | Calcium ChlorideMagnesium SulphatePotassium ChloridePotassium PhosphateSodium Chloride |
| Amino Acids | Yes | Yes | Yes |
Table 1 Comparison of SAGE 1-Step™ with the predicate Global® Total®
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| Product | SAGE 1-Step™(REF 6701) | SAGE 1-Step™(REF 6702) | Global® Total® |
|---|---|---|---|
| Stable form of L-Glutamine | Alanyl-Glutamine | Alanyl-Glutamine | Glycyl-Glutamine |
| Energy sources | GlucoseCalcium-L-LactateSodium Pyruvate | GlucoseCalcium-L-LactateSodium Pyruvate | GlucoseSodium-DL-LactateSodium Pyruvate |
| EDTA | Yes | Yes | Yes |
| Buffer | Sodium Bicarbonate | Sodium Bicarbonate | Sodium Bicarbonate |
| Phenol Red | Yes | Yes | Yes |
| Sodium hyaluronate | 0.1 mg/mL | - | - |
| Protein source | |||
| HSA (proteins: albumin) | 5 mg/mL | - | |
| PPF (proteins: albumin, α- and β-globulins) | - | 5 mg/mL | - |
| LGPS (proteins: albumin, α- and β-globulins) | - | - | 5 mg/mL |
| Drugs | |||
| Gentamicin sulphate | 0.01 mg/mL | 0.01 mg/mL | 0.01 mg/mL |
The base medium of SAGE 1-Step™, as well as the predicate, is similar to the first single-step medium developed by Lawitts and Biggers (1991) and later supplemented with amino acids.
The technological characteristics of SAGE 1-Step™ are comparable to those of the predicate device. The main differences are:
- Protein supplementation: SAGE 1-Step™ is available in two ready-to-use formulations with . either Serum Protein Supplementation (REF 6702) or Human Serum Albumin (REF 6701) as protein source. The protein source of the predicate is LGPS which is similar to Serum Protein Supplementation as they both contain albumin and globulins. Human Serum Albumin is different from the protein source in the predicate, it is however a standard protein supplement used in other cleared devices for continuous culture such as Irvine Scientific Continuous Single Culture Complete (K121572).
- Sodium Hyaluronate: SAGE 1-Step™ supplemented with Human Serum Albumin is further . added Sodium Hyaluronate as a supplement to albumin. Sodium Hyaluronate is a well known component in other ART media (VitroLifes G-series (K081114, K081117, K031015)) and hyaluronan is naturally found in the female reproductive tract. Thus the addition of Sodium Hyaluronate in SAGE 1-Step™ supplemented with Human Serum Albumin (REF 6701) is not considered to represent a new technology when compared to the predicate.
- Lactate: SAGE 1-Step™ contains Ca-L-Lactate whereas the predicate contains Na-DL-. Lactate.. The concentration of L-lactate in SAGE 1-Step™ is comparable with the concentration of L-lactate in the predicate.
- Magnesium Sulphate is added in a higher concentration compared to the predicate. . However other culture media e.g Quinn 's Advantage media (K002836) also contain higher concentrations of Magnesium Sulphate and it is judged that it will not influence the performance or safety compared to the predicate device .
- Calcium: Calcium is added in the form of Ca-Lactate whereas the predicate contains Na-. Lactate. The Calcium concentration in SAGE 1-Step™ is similar to the predicate and therefore it has no impact.
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- Stable L-Glutamine: Both SAGE 1-Step™ and the predicate contains a stable form of glutamine. Both Alanyl-Glutamine used in SAGE 1-STEP™ and Glycyl-Glutamine used in the predicate are widely used in ART media and have a history of safe use.
The differences in composition do not impact the substantial equivalence and do not raise any new types of safety or effectiveness concern.
Performance data
The product specifications for SAGE 1-Step™ and the predicate are similar regarding sterility, pH, and Mouse Embryo Assay (MEA) test. However, the endotoxin levels varies. Endotoxin is <0.50 EU/mL for Global® Total®. For SAGE 1-Step™ the endotoxin limit is <0.15 EU/mL.
Regarding the osmolality, the specification limit is a bit wider for SAGE 1-Step™ (257-273 mOsm/kg) than for the predicate (260-270 mOsm/kg).
The shelf life of SAGE 1-Step™ has been validated in stability studies to 14 weeks. The parameters which have been tested in the stability studies through shelf life includes pH, osmolality, endotoxin. HSA concentration, MEA, and sterility.
In general, SAGE 1-Step" medium is subject to the same control methods and, to a significant dearee, contain the same components as the predicate device. SAGE 1-Step™ has similar handling procedures and storage conditions. Therefore, SAGE 1-Step™ is considered substantially equivalent to the predicate device Global® Total®.
Biocompatibility
SAGE 1-Step™ is categorized as a medium in direct contact with gametes and embryos from OHOE Y-otep " is categorized as a median in direct contact with gameter and childryou franser, it is also in direct contact with the uterus (patient). The biological safety evaluation (ISO 10993-1) demonstrates that SAGE 1-Step™ medium, consist of well tested components and is non-toxic in use. SAGE 1-Step™ is therefore considered safe for fertilization and culture of human gametes and embryos as well as transfer of embryos back into the patient (uterus).
Conclusion
The conclusion from the performance and safety data, intended use comparison, product formulation comparison, and test specification comparison, demonstrates that the SAGE 1-Step™ supplemented with Human Serum Albumin and SAGE 1-Step™ supplemented with Serum Protein Supplement are suitable for its intended use, and meets the criteria in the comparison to the predicate device LifeGlobal Global® Total® (K112083).
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Image /page/4/Picture/0 description: The image shows the logo for the Department of Health & Human Services - USA. The logo is circular, with the text "DEPARTMENT OF HEALTH & HUMAN SERVICES - USA" arranged around the perimeter. Inside the circle is a stylized symbol that resembles a person embracing another person, or a stylized caduceus.
DEPARTMENT OF HEALTH & HUMAN SERVICES
Public Health Service
Food and Drug Administration 10903 New Hampshire Avenue Document Control Center - WO66-G609 Silver Spring, MD 20993-0002
April 16, 2014
ORIGIO a/s Tove Kjaer Director Corporate Regulatory Affairs Knardrupvej 2 Måløv 2760 Denmark
Re: K133707
Trade/Device Name: SAGE 1-Step™ supplemented with Human Serum Albumin and SAGE 1-Step™ supplemented with Serum Protein Supplement Regulation Number: 21 CFR§ 884.6180 Regulation Name: Reproductive media and supplements Regulatory Class: II Product Code: MQL Dated: March 17, 2014 Received: March 19, 2014
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 aboye) 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 Kjaer
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 (OS) 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/ReportalProblem/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,
Image /page/5/Picture/7 description: The image shows the word "Benjamin" followed by the letters "FDA" in a stylized font. The letters "FDA" are enclosed in a box-like shape. The word "sher-S" is written after the letters "FDA".
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
Form Approved: OMB No. 0910-0120 Expiration Date: December 31, 2013 See PRA Statement on last page.
510(k) Number (if known) K 133707
Device Name
SAGE I-Step™ with Human Serum Albumin and SAGE 1-Step™ with Serum Protein Supplement
Indications for Use (Describe)
These products are intended for the in vitro fertilization and culture of human gametes and embryos from fertilization uni! Day 5/6 of development. The media can also be used for transfer.
Type of Use (Select one or both, as applicable)
D 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.
BARTER FOR FOR USE ONLY TO A WARRELLER FOR SELECT FOR A BEA 2017 11 ------------------------------------------------------------------------------------------------------------------------------------------------------------------------------(· Concurrence of Center for Devices and Radiological Health (CDRH) (Signature)
Concurrence of Center for Devices and Radiological Health (CDRH) [signature]
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FORM FDA 3881 (9/13)
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§ 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.