CUMULASE

K042495 · Halozyme Therapeutics, Inc. · MQL · Apr 14, 2005 · Obstetrics/Gynecology

Device Facts

• Record ID: K042495
• Device Name: CUMULASE
• Applicant: Halozyme Therapeutics, Inc.
• Product Code: MQL · Obstetrics/Gynecology
• Decision Date: Apr 14, 2005
• Decision: SESE
• Submission Type: Traditional
• Regulation: 21 CFR 884.6180
• Device Class: Class 2

Intended Use

Cumulase™ is indicated for use in removing the cumulus matrix surrounding oocytes in preparation for assisted reproduction technology (ART) procedures.

Device Story

Cumulase™ is a recombinant human hyaluronidase (rHuPH20) enzyme solution in a HEPES buffered salt solution. It is used in clinical laboratory settings during assisted reproduction technology (ART) procedures to enzymatically remove the cumulus matrix surrounding oocytes. The device is intended for use by trained embryologists or clinical laboratory personnel. By facilitating the removal of the cumulus cells, the device prepares oocytes for subsequent procedures such as intracytoplasmic sperm injection (ICSI). The product is provided as a non-preserved solution, manufactured using recombinant human biotechnology to avoid animal-derived components.

Clinical Evidence

No clinical data provided. Evidence consists of bench testing and product characterization, including enzymatic activity (USP Assay), pH (USP <791>), endotoxin (USP <85>), osmolality (USP <785>), sterility (USP <71>), and mouse embryo assay (one-cell).

Technological Characteristics

Recombinant human hyaluronidase (rHuPH20) in HEPES buffered salt solution. Biocompatibility qualified per ISO 10993. Control testing follows USP standards for enzymatic activity, pH, endotoxin, osmolality, and sterility. Animal-component free. Non-preserved.

Indications for Use

Indicated for use in removing the cumulus matrix surrounding oocytes in preparation for assisted reproduction technology (ART) procedures.

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

• Medi-Cult Hyaluronidase (K991334)

Submission Summary (Full Text)

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## APR 1 4 2005

| Appendix III | |
|--------------|--|
| | |

## 510(k) Premarket Notification Summary B.5

| Submitted by: | Halozyme Therapeutics Inc<br>11588 Sorrento Valley Road, #17<br>San Diego, Ca 92121 |
|--------------------------------|-------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|
| Contact Person: | Mr. Don Kennard<br>Halozyme Therapeutics Inc.<br>11588 Sorrento Valley Road, #17<br>San Diego, Ca 92121 |
| Trade name: | Cumulase™ Catalog<br>Number H4001 |
| Common name: | Hyaluronidase |
| Classification name: | Reproductive Media and<br>Supplements<br>(21 CFR § 884.6180) |
| Predicate Device: | Medi-Cult Hyaluronidase<br>(510(k) # K991334 |
| Description of the Device: | Recombinant Human<br>Hyaluronidase Solution |
| Intended use: | Cumulase™ is indicated for use in<br>removing the cumulus matrix<br>surrounding oocytes in<br>preparation for assisted<br>reproduction technology (ART)<br>procedures. |
| Technological Characteristics: | Cumulase™ differs slightly from<br>the predicate device. Specifically<br>Cumulase™ uses a recombinant<br>human biotechnology developed<br>source of hyaluronidase enzymatic<br>activity instead of a bovine<br>testicular derived source. |

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| Product Formulation: | |
|------------------------------------------------------------------------------------------------------------------------------------|-----------|
| Cumulase™ is a hyaluronidase enzyme in a HEPES buffered salt solution. | |
| The hyaluronidase enzyme raw material is a highly characterized biotechnology developed recombinant human hyaluronidase (rHuPH20). | |
| Cumulase™ is not preserved. | |
| Product Characterization: | |
| rHuPH20 Hyaluronidase has been extensively characterized to International Committee on Harmonization regulatory requirements. | |
| rHuPH20 Hyaluronidase manufacturing process media is chemically defined and is free of animal derived components or materials | |
| Cumulase™ has been qualified to ISO 10993 standards for biocompatibility | |
| Product Control Testing | |
| Enzymatic Activity | USP Assay |
| pH | USP <791> |
| Endotoxin | USP <85> |
| Osmolality | USP <785> |
| Sterility | USP <71> |
| Mouse Embryo Assay | One Cell |

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Image /page/2/Picture/2 description: The image shows the logo for the U.S. Department of Health & Human Services. The logo consists of a stylized eagle with three tail feathers, representing the department's commitment to health, human services, and well-being. The text "DEPARTMENT OF HEALTH & HUMAN SERVICES - USA" is arranged in a circular pattern around the eagle.

APR 1 4 2005

Food and Drug Administration 9200 Corporate Boulevard Rockville MD 20850

Mr. Don Kennard Vice President Regulatory and Quality Affairs Halozyme Therapeutics, Inc. 11588 Sorrento Valley Road, Suite 17 SAN DIEGO CA 92121

Re: K042495

Trade/Device Name: Cumulase™ Regulation Number: 21 CFR 884.6180 Regulation Name: Reproductive media and supplements

Regulatory Class: II Product Code: MQL Dated: April 1, 2005 Received: April 4, 2005

Dear Mr. Kennard:

We have reviewed your Section 510(k) premarket notification of intent to market the device referenced we have reviewed your bocurent by equivalent (for the indications for use stated in above and nave decemininarketed predicate devices marketed in interstate commerce prior to the cliciosale) to tegarry manteers production Device Amendments, or to devices that have been May 20, 1770, the charance 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 do not require approval of a provisions of the Act. The general controls provisions of the Act device, subject to the general controls prove, listing of devices, good manufacturing practice, labeling, and prohibitions against misbranding and adulteration.

If your device is classified (see above) into either class II (Special Controls) or class III (Premarket If your device is classinod (600 a0010) hitional controls. Existing major regulations affecting your Apploval), it thay be subject to outinateral Regulations, Title 21, Parts 800 to 898. In addition, FDA device build be found in nouncements concerning your device in the Federal Register.

Please be advised that FDA's issuance of a substantial equivalence determination does not mean that FIEase be advised mar 1271's issualled on aevice complies with other requirements of the Act or any Federal statutes and regulations administered by other Federal agencies. You must comply with all the Federal statues and regulations as ammitived to registration and listing (21 CFR Part 807); labeling Act s requirements, mediating practice requirements as set forth in the quality systems (QS) (21 CFK Fall 801), good manufacturing practice the electronic product radiation control provisions (Sections 531-542 of the Act); 21 CFR 1000-1050.

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This letter will allow you to begin marketing your device as described in your Section 510(k)
10 Jegal This letter will allow you to begin hanketing your interess of your device to a legally premarket notification. The FDA inding of subscification for your device and thus, permits your device to proceed to the market.

If you desire specific advice for your device on our labeling regulation (21 CFR Part 801), pleased If you desire specific advice for your device on our labering organises (
contact the Office of Compliance at one of the following numbers, based on the regulation number at the top of this letter:

| 21 CFR 876.xxxx | (Gastroenterology/Renal/Urology) | 240-276-0115 |
|-----------------|----------------------------------|--------------|
| 21 CFR 884.xxxx | (Obstetrics/Gynecology) | 240-276-0115 |
| 21 CFR 892.xxxx | (Radiology) | 240-276-0120 |
| Other | | 240-276-0100 |

Also, please note the regulation entitled, "Misbranding by reference to premarket notification" (21 CFR Also, please note the regulation entitled, "Misonomians" of the mider the Act from the 807.97). You may obtain other general information on your respections at its toll-free number (800) DIVISion of Dinal July 443-6597 or at its Internet address 056-2041 or (50 gov/cdrh/industry/support/index.html.

Sincerely yours,

Nancy C. Brogdon

Nancy C. Brogdon Director, Division of Reproductive, Abdominal, and Radiological Devices Office of Device Evaluation Center for Devices and Radiological Health

Enclosure

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Halozyme Therapeutics

Confidential

Volume l

## Indications for Use Statement C.4

| 510(k) Number | (if known): K042495 |
|----------------------|---------------------------------------------------------------------------------------------------------------------------------------------------------|
| Device Name: | Cumulase™ |
| Indications for Use: | Cumulase™ is indicated for use in removing the cumulus matrix surrounding oocytes in preparation for assisted reproduction technology (ART) procedures. |

Prescription Use X (Part 21 CFR 801 Subpart D)

AND/OR

Over-The-Counter Use (21 CFR 801 Subpart C)

(PLEASE DO NOT WRITE BELOW THIS LINE-CONTINUE ON ANOTHER PAGE OF NEEDED)

Concurrence of CDRH, Office of Device Evaluation (ODE)

David A. Lynn

(Division Sign-Off) Division of Reproductive, Abdominal, and Radiological Devices

510(k) Number _

Cumulase 510K Page 18