BlastGen

K152932 · Origio A/S · MQL · Feb 29, 2016 · Obstetrics/Gynecology

Device Facts

• Record ID: K152932
• Device Name: BlastGen
• Applicant: Origio A/S
• Product Code: MQL · Obstetrics/Gynecology
• Decision Date: Feb 29, 2016
• Decision: SESE
• Submission Type: Traditional
• Regulation: 21 CFR 884.6180
• Device Class: Class 2

Intended 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.

Device Story

BlastGen™ is a reproductive culture medium used in assisted reproduction clinics by embryologists. It is a modification of the predicate ORIGIO® Sequential Blast™ (K133387) formulated with the addition of Leukine (Sargramostim), a granulocyte macrophage colony-stimulating factor (GM-CSF). The device serves as a growth environment for embryos from the 4-8 cell stage to the blastocyst stage and is also used during embryo transfer. By providing GM-CSF, the medium aims to improve embryo developmental competence, reduce apoptosis, and increase viable inner cell mass cells, potentially enhancing implantation and pregnancy rates. The solution is provided in glass bottles and is ready for use by professionals.

Clinical Evidence

Evidence includes a prospective randomized sibling zygote pilot study (n=371 zygotes) comparing GM-CSF-containing media to control media, showing trends toward higher blastocyst rates, pregnancy rates, and ongoing implantation rates. Supporting literature (Sjöblom et al., 1999; 2002) indicates GM-CSF increases blastocyst development (30% to 76%), improves developmental competence, reduces apoptotic nuclei by 50%, and increases inner cell mass cells by 30%.

Technological Characteristics

Ready-to-use, non-viscous liquid medium. Contains GM-CSF (Sargramostim) and human serum albumin (HSA). Quality control includes ELISA for GM-CSF/HSA, TF-1 cell assay for GM-CSF potency, and Mouse Embryo Assay. Sterilization via aseptic filtration validated per EN/ISO 13408-2:2011 (SAL 10^-3). Biocompatibility testing conducted per ISO 10993-1:2009.

Indications for Use

Indicated for the culture of embryos from the 4-8 cell stage through to the blastocyst stage and for embryo transfer in patients undergoing assisted reproduction.

Regulatory Classification

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.).

Special Controls

*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.

Predicate Devices

• ORIGIO® Sequential Blast™ (Cat. No. 8305) (K133387)

Submission Summary (Full Text)

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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

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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 [phone] or [phone] 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 [phone] or [phone] or at its Internet address

http://www.fda.gov/MedicalDevices/ResourcesforYou/Industry/default.htm.

Sincerely yours,

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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

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) | |
|-------------------------------------------------------------------------------------------------|-------------------------------------------------------------------------------------|
| <label><input checked="" type="checkbox"/> Prescription Use (Part 21 CFR 801 Subpart D)</label> | <label><input type="checkbox"/> Over-The-Counter Use (21 CFR 801 Subpart C)</label> |

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## K152932 - BlastGen™

## 510(k) SUMMARY

| Submitted by: | ORIGIO a/s<br>Knardrupvej 2,<br>2760 Måløv,<br>Denmark |
|-----------------|------------------------------------------------------------------|
| Contact Person: | Tove Kjær<br>Director Corporate Regulatory Affairs<br>ORIGIO a/s |
| | Phone: [phone]<br>Fax: [phone] |
| | 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, Product<br>Code 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).

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).

### 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

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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.