(212 days)
Cumulase™ is indicated for use in removing the cumulus matrix surrounding oocytes in preparation for assisted reproduction technology (ART) procedures.
Recombinant Human Hyaluronidase Solution
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.
The provided document describes the Cumulase™ device, a recombinant human hyaluronidase solution intended for use in assisted reproduction technology (ART) procedures. The document focuses on the device's technical specifications and regulatory clearance, rather than a clinical study evaluating its performance against specific acceptance criteria.
Therefore, I cannot directly extract details about a study demonstrating the device meets acceptance criteria in the format requested, as the information is not present in the provided text. The document is a 510(k) premarket notification summary, which primarily establishes substantial equivalence to a predicate device and outlines manufacturing and characterization rather than a clinical performance study with predefined acceptance criteria.
However, I can infer some aspects based on the available information:
1. A table of acceptance criteria and the reported device performance:
The document lists "Product Control Testing" which can be interpreted as internal quality control acceptance criteria. However, it does not provide performance results against these criteria in a comparative table for a specific study.
| Acceptance Criteria (Product Control Testing) | Reported Device Performance (Not explicitly stated in this document as performance results from a study) |
|---|---|
| Enzymatic Activity (USP Assay) | Expected to pass, but specific results not available. |
| pH (USP <791>) | Expected to fall within an acceptable range, but specific results not available. |
| Endotoxin (USP <85>) | Expected to be within limits, but specific results not available. |
| Osmolality (USP <785>) | Expected to be within limits, but specific results not available. |
| Sterility (USP <71>) | Expected to be sterile, but specific results not available. |
| Mouse Embryo Assay (One Cell) | Expected to demonstrate non-toxicity/suitability, but specific results not available. |
The document states: "rHuPH20 Hyaluronidase has been extensively characterized to International Committee on Harmonization regulatory requirements." and "Cumulase™ has been qualified to ISO 10993 standards for biocompatibility." This indicates that these criteria were met, but specific data is not provided.
The "study that proves the device meets the acceptance criteria" is not described in detail as a standalone clinical performance study with statistical results. The 510(k) process primarily relies on demonstrating substantial equivalence to a predicate device (Medi-Cult Hyaluronidase, 510(k) # K991334) through characterization and quality control, rather than a prospective clinical trial.
Based on the provided information, the following questions cannot be answered as the relevant data is not present:
- Sample sized used for the test set and the data provenance: Not applicable as a clinical "test set" for performance evaluation is not described in this document.
- Number of experts used to establish the ground truth for the test set and the qualifications of those experts: Not applicable.
- Adjudication method: Not applicable.
- 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 biological solution, not an AI or imaging device requiring human reader interpretation.
- If a standalone (i.e. algorithm only without human-in-the-loop performance) was done: Not applicable.
- The type of ground truth used: For the quality control tests listed, the ground truth would be the established USP standards and ISO 10993 requirements for each parameter.
- The sample size for the training set: Not applicable as this is not an AI/machine learning device.
- How the ground truth for the training set was established: Not applicable.
Summary of available information related to the device's characteristics and "demonstration of meeting criteria":
- Technological Characteristics: Cumulase™ uses a recombinant human biotechnology-developed source of hyaluronidase enzymatic activity, distinguishing it from the bovine testicular derived source of the predicate device.
- Product Formulation: Hyaluronidase enzyme in a HEPES buffered salt solution, unpreserved. The raw material is rHuPH20, extensively characterized to ICH regulatory requirements.
- Manufacturing Process: Chemically defined and free of animal-derived components or materials.
- Biocompatibility: Qualified to ISO 10993 standards.
- Product Control Testing (Acceptance Criteria): Enzymatic Activity (USP Assay), pH (USP <791>), Endotoxin (USP <85>), Osmolality (USP <785>), Sterility (USP <71>), Mouse Embryo Assay (One Cell). The implication is that the product consistently meets these internal specifications.
- Predicated Device: Medi-Cult Hyaluronidase (510(k) # K991334). The 510(k) process for Cumulase™ is based on demonstrating substantial equivalence to this device.
The provided text serves as a regulatory submission document for market clearance, highlighting the safety and effectiveness of the device through characterization and comparison to a legally marketed predicate, rather than a detailed report of a clinical performance study against quantified acceptance criteria.
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APR 1 4 2005
| Appendix III | |
|---|---|
510(k) Premarket Notification Summary B.5
| Submitted by: | Halozyme Therapeutics Inc11588 Sorrento Valley Road, #17San Diego, Ca 92121 |
|---|---|
| Contact Person: | Mr. Don KennardHalozyme Therapeutics Inc.11588 Sorrento Valley Road, #17San Diego, Ca 92121 |
| Trade name: | Cumulase™ CatalogNumber H4001 |
| Common name: | Hyaluronidase |
| Classification name: | Reproductive Media andSupplements(21 CFR § 884.6180) |
| Predicate Device: | Medi-Cult Hyaluronidase(510(k) # K991334 |
| Description of the Device: | Recombinant HumanHyaluronidase Solution |
| Intended use: | Cumulase™ is indicated for use inremoving the cumulus matrixsurrounding oocytes inpreparation for assistedreproduction technology (ART)procedures. |
| Technological Characteristics: | Cumulase™ differs slightly fromthe predicate device. SpecificallyCumulase™ uses a recombinanthuman biotechnology developedsource of hyaluronidase enzymaticactivity instead of a bovinetesticular 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
§ 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.