← Product Code [MQL](/submissions/OB/subpart-g%E2%80%94assisted-reproduction-devices/MQL) · K182002 # Cumulus Remover (K182002) _Kitazato Corporation · MQL · Oct 23, 2018 · Obstetrics/Gynecology · SESE_ **Canonical URL:** https://fda.innolitics.com/submissions/OB/subpart-g%E2%80%94assisted-reproduction-devices/MQL/K182002 ## Device Facts - **Applicant:** Kitazato Corporation - **Product Code:** [MQL](/submissions/OB/subpart-g%E2%80%94assisted-reproduction-devices/MQL.md) - **Decision Date:** Oct 23, 2018 - **Decision:** SESE - **Submission Type:** Traditional - **Regulation:** 21 CFR 884.6180 - **Device Class:** Class 2 - **Review Panel:** Obstetrics/Gynecology ## Intended Use Cumulus Remover is for the removal of the cumulus complex and corona radiata surrounding the oocyte in preparation for ICSI. ## Device Story Cumulus Remover is an enzyme solution containing recombinant human hyaluronidase used to digest hyaluronic acid binding cumulus and corona cells to oocytes. It is utilized in clinical laboratory settings by embryologists prior to ICSI fertilization procedures. The solution facilitates the denuding of oocytes, which is a necessary step for successful sperm injection. The device is provided in polypropylene vials and is intended for professional use in assisted reproduction laboratories. By effectively removing the surrounding cell layers, the device enables the clinician to visualize and access the oocyte for the ICSI procedure, thereby supporting the fertilization process. ## Clinical Evidence Bench testing only. Testing included pH (USP <791>), osmolality (USP <785>), sterility (USP <71>), endotoxin (USP <85>), and hyaluronidase activity (Japanese Pharmacopoeia JP17). Aseptic processing validated per ISO 13408-1:2015 and ISO 13408-2:2003. Mouse embryo assay (MEA) performed: one-cell mouse embryos exposed to device and cultured at 37°C/5% CO2; acceptance criteria ≥80% development to expanded blastocyst stage within 96 hours. Shelf-life testing conducted for six months. ## Technological Characteristics Enzyme solution containing recombinant human hyaluronidase, physiological salts, energy substances, HEPES buffer, human albumin, gentamicin, and dextran. pH 7.2-7.6; osmolality 270-295 mOsm; hyaluronidase activity 70-90 units/ml. Provided in 0.5 mL polypropylene vials. Aseptically processed. Shelf-life 6 months at 2-8°C. ## Regulatory 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 - ICSI Cumulase ([K081639](/device/K081639.md)) ## Related Devices - [K200680](/device/K200680.md) — Synvitro Hyadase · Origio A/S, A Coopersurgical Company · Jul 17, 2020 - [K991393](/device/K991393.md) — HYALURONIDASE, 80 U/ML · Sage Biopharma · Feb 2, 2000 - [K011573](/device/K011573.md) — HYALURONIDASE IN HTF MEDIUM; HYALURONIDASE IN EBSS MEDIUM · Conception Technologies · Jul 2, 2001 - [K042495](/device/K042495.md) — CUMULASE · Halozyme Therapeutics, Inc. · Apr 14, 2005 - [K060699](/device/K060699.md) — SYNVITRO CUMULASE (HYALURONIDASE MEDIUM) · Medicult A/S · May 10, 2006 ## Submission Summary (Full Text) {0}------------------------------------------------ Image /page/0/Picture/0 description: The image shows the logo of the U.S. Food and Drug Administration (FDA). The logo consists of two parts: the Department of Health & Human Services logo on the left and the FDA logo on the right. The FDA logo features the letters "FDA" in a blue square, followed by the words "U.S. FOOD & DRUG ADMINISTRATION" in blue text. October 23, 2018 Kitazato Corporation % Audrey Swearingen Manager. Regulatory Affairs Emergo Global Consulting, LLC 2500 Bee Cave Road Building 1, Suite 300 Austin, TX 78746 Re: K182002 Trade/Device Name: Cumulus Remover Regulation Number: 21 CFR 884.6180 Regulation Name: Reproductive media and supplements Regulatory Class: Class II Product Code: MQL Dated: July 25, 2018 Received: July 26, 2018 Dear Audrey Swearingen: 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. Although this letter refers to your product as a device, please be avare that some cleared products may instead be combination products. The 510(k) Premarket Notification Database located at https://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfpmn/pmn.cfm identifies combination product submissions. 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. {1}------------------------------------------------ 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) for devices or postmarketing safety reporting (21 CFR 4, Subpart B) for combination products (see https://www.fda.gov/CombinationProducts/GuidanceRegulatoryInformation/ucm597488.htm); good manufacturing practice requirements as set forth in the quality systems (OS) regulation (21 CFR Part 820) for devices or current good manufacturing practices (21 CFR 4, Subpart A) for combination products; and, if applicable, the electronic product radiation control provisions 531-542 of the Act); 21 CFR 1000-1050. 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 comprehensive regulatory information about medical devices and radiation-emitting products, including information about labeling regulations, please see Device Advice (https://www.fda.gov/MedicalDevices/DeviceRegulationandGuidance/) and CDRH Learn (http://www.fda.gov/Training/CDRHLearn). Additionally, you may contact the Division of Industry and Consumer Education (DICE) to ask a question about a specific regulatory topic. See the DICE website (http://www.fda.gov/DICE) for more information or contact DICE by email (DICE@fda.hhs.gov) or phone (1-800-638-2041 or 301-796-7100). Sincerely. Michael T. Bailey -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 {2}------------------------------------------------ ## Indications for Use 510(k) Number (if known) K182002 Device Name Cumulus Remover #### Indications for Use (Describe) Cumulus Remover is for the removal of the cumulus complex and corona radiata surrounding the oocyte in preparation for ICSI. | Type of Use (Select one or both, as applicable) | | |-------------------------------------------------|-----------------------------------------------------| | Prescription Use (Part 21 CFR 801 Subpart D) | <div> <span style="font-size:100%;">☒</span> </div> | | Over-The-Counter Use (21 CFR 801 Subpart C) | <div> <span style="font-size:100%;">☐</span> </div> | #### 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}------------------------------------------------ # 510(k) Summary Cumulus Remover K182002 #### 1. Submission Sponsor Kitazato Corporation 81 Fuji Shizuoka 416-0907 JAPAN Phone number: +(81) 545-66-2202 Contact: Mr. Futoshi Inoue Title: President #### 2. Submission Correspondent Emergo Global Consulting, LLC 2500 Bee Cave Road Building 1, Suite 300 Austin, TX 78746 Office Phone: (512) 327-9997 Contact: Audrey Swearingen, RAC Title: Director, Regulatory Affairs #### 3. Date Prepared October 23, 2018 #### 4. Device Identification | Trade name: | Cumulus Remover | |--------------------|------------------------------------| | Common name: | Hyaluronidase Solution | | Regulation name: | Reproductive Media and Supplements | | Regulation number: | 21 CFR 884.6180 | | Product code: | MQL (Media, Reproductive) | | Regulatory class: | II | #### 5. Predicate Device ICSI Cumulase (K081639) manufactured by MediCult a/s. This predicate device is now branded by Origio a/s and has not been subject to any design related recalls. {4}------------------------------------------------ #### 6. Device Description Cumulus Remover is an enzyme solution containing recombinant human hyaluronidase that digests hyaluronic acid that binds the cumulus and corona cells surrounding oocytes together. This function of hyaluronidase can be used for denuding cumulus and coronal cells from oocytes prior to performing Intracytoplasmic Sperm Injection (ICSI) fertilization procedures. Cumulus Remover is provided in a polypropylene vial (package size 0.5 mL), and five vials are packaged together in a box. This product is aseptically processed and has a shelf-life of six months when stored at 2-8°C. Cumulus Remover is tested for pH, osmolality, endotoxin, sterility, embryotoxicity, and hyaluronidase activity before lot release. #### 7. Indication for Use Cumulus Remover is for the removal of the cumulus complex and corona radiata surrounding the oocyte in preparation for ICSI. | Device | K182002 (subject device) | K081639 (predicate device) | |------------------------|---------------------------------------------------------------------------------------------------------------------------------------|---------------------------------------------------------------------------------------------------------------------------------| | Indications for Use | Cumulus Remover is for the removal of<br>the cumulus complex and corona radiata<br>surrounding the oocyte in preparation<br>for ICSI. | ICSI Cumulase is for the removal of<br>cumulus complex and corona radiata<br>surrounding the oocyte in preparation<br>for ICSI. | | pH | 7.2-7.6 | Information is not available | | Osmolality | 270-295 mOsm | Information is not available | | Hyaluronidase activity | 70-90 units/ml (average 80 units/ml) | 40-120 units/ml (average 80 units/ml) | | Formulation | Physiological salts | Physiological salts | | | Energy substance | Energy substance | | | Buffering substance (HEPES) | Buffering substance (HEPES) | | | Recombinant human hyaluronidase | Recombinant human hyaluronidase | | | Human albumin | Human albumin | | | Gentamicin | | | | Dextran | | #### 8. Substantial Equivalence Discussion The subject and predicate devices have the same indications for use/intended use; however, there are differences in technological characteristics. Although the subject and predicate devices possess different ranges of hyaluronidase activity, the activity range of the subject device falls within the activity range of the predicate and both devices have the same average hyaluronidase activity (80 units/ml). Regarding formulation, the subject and predicate devices have the same or comparable salts, energy substance, and buffering agents. The subject device is different from the predicate device in that it contains gentamicin and dextran. These differences in formulation do not raise different questions of safety and effectiveness. In addition, the pH and osmolality values for the predicate device are not known; however, differences in pH and osmolality are common in assisted reproduction media products and do not raise different questions of safety and effectiveness. Also, the subject device pH and osmolality ranges are comparable to other assisted reproduction media products. ### 9. Summary of Non-Clinical Performance Testing The following studies have been performed to support substantial equivalence to the predicate devices: {5}------------------------------------------------ - pH testing per USP <791> See table above . - Osmolality per USP <785> See table above . - Aseptic Processing Validation per ISO 13408-1:2015 and ISO 13408-2:2003 . - Sterility testing per USP <71> No microbial growth . - . Endotoxin testing per USP <85> - <0.25 EU/ml - Mouse embryo assay (MEA) . 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 expanded blastocyst stage within 96 hours were assessed in comparison with the control group. The acceptance specification is that ≥80% of embryos expand to the blastocyst stage by 96h. - . Hyaluronidase activity - 70-90 units/ml (per Japanese Pharmacopoeia, JP17) - Shelf-life testing was conducted to ensure that the following product specifications are met at time . zero and end of shelf-life (six months). - * pH - * Osmolality - * 1-cell MEA - * Endotoxin - * Sterility - * Hyaluronidase activity #### 10. Conclusion The subject and predicate devices have the same intended use and comparable technological characteristics. The differences in technological characteristics between the subject and predicate devices do not raise different questions of safety and effectiveness. The performance data demonstrate that the subject device is substantially equivalent to the predicate device. --- **Source:** [https://fda.innolitics.com/submissions/OB/subpart-g%E2%80%94assisted-reproduction-devices/MQL/K182002](https://fda.innolitics.com/submissions/OB/subpart-g%E2%80%94assisted-reproduction-devices/MQL/K182002) **Published by [Innolitics](https://innolitics.com)** — a medical-device software consultancy. We help companies design, build, and clear FDA-regulated software and AI/ML devices. If you're preparing [a 510(k)](https://innolitics.com/services/510ks/), [a De Novo](https://innolitics.com/services/regulatory/), [a SaMD](https://innolitics.com/services/end-to-end-samd/), [an AI/ML medical device](https://innolitics.com/services/medical-imaging-ai-development/), or [an FDA regulatory strategy](https://innolitics.com/services/regulatory/), [get in touch](https://innolitics.com/contact). **Cite as:** FDA Device Explorer (Innolitics), https://fda.innolitics.com/submissions/OB/subpart-g%E2%80%94assisted-reproduction-devices/MQL/K182002