HYHUB™ and HYHUB™ Duo vial access devices are indicated for patients 17 years of age or older to allow a drug to be transferred from vials without using a needle, as prescribed, in a home environment or clinical setting.

Device Description

The HYHUB™ and HYHUB™ DUO vial access devices (VAD) are a stand-alone, single-use, disposable, non-pyrogenic, gamma sterilized device, which are intended to support the infusion of two medicinal liquids, as prescribed, in a home environment or clinical setting. The VAD is designed to accommodate up to two (2) or four (4) dual vial units (DVU) to be docked onto the VAD infusion tray which allows the transfer of medicinal liquids in a sequential, needleless manner using standard connections for syringes, applicable pumps, and infusion sets.

AI/ML Overview

The FDA 510(k) clearance letter for the HyHub™ and HyHub™ Duo Vial Access Devices (K243404) does not contain the level of detail typically found in a clinical study report or a summary of clinical performance for AI/ML-based devices. Instead, it focuses on demonstrating substantial equivalence to a predicate device through bench testing, biocompatibility testing, and a comparison of technological characteristics.

Therefore, many of the requested categories relating to acceptance criteria for AI inference, dedicated test sets, expert adjudication, MRMC studies, standalone algorithm performance, and detailed training data are not applicable or cannot be extracted from this document. The document describes a medical device, not an AI/ML algorithm.

However, I can extract the information relevant to the performance testing that was conducted to demonstrate this device meets its requirements for substantial equivalence.

1. Table of Acceptance Criteria and Reported Device Performance

For a traditional medical device like the HyHub, "acceptance criteria" are generally tied to meeting specific performance standards based on recognized test methods or internal protocols. The document does not explicitly state numerical acceptance criteria for each test alongside performance data in a single table, but it lists the tests performed and implies successful completion for substantial equivalence.

Since the document does not provide specific numerical acceptance criteria and reported performance results for each test (e.g., maximum allowable leak rate vs. measured leak rate), I can only present the categories of tests performed.

Acceptance Criteria Category (Bench Test)	Reported Device Performance (Summary Statement)
Leak test	Performed successfully, demonstrating the device functions as intended.
Particulate test	Performed successfully, demonstrating the device functions as intended.
Luer connectors compatibility	Performed successfully, demonstrating the device functions as intended.
Stopper fragmentation test	Performed successfully, demonstrating the device functions as intended.
Sterile packaging test	Performed successfully, demonstrating the device functions as intended.
Flow test	Performed successfully (supported pump compatibility, intended use).
Residual/Injectable Volume test	Performed successfully (supported pump compatibility, intended use).
Human Factors Validation	Performed successfully, demonstrating the device functions as intended.

2. Sample Size Used for the Test Set and Data Provenance

This information is not provided in the FDA 510(k) letter. The document mentions "bench tests" and "biocompatibility evaluation," implying a set of physical devices were tested rather than a "test set" of data in the AI/ML context. No details on the number of units tested per bench test are given, nor is information on geographical origin or retrospective/prospective nature of data for this type of hardware device.

3. Number of Experts Used to Establish Ground Truth and Qualifications

This information is not applicable for this type of device and submission. The "ground truth" for a vial access device is its physical performance against established engineering and biocompatibility standards, not expert interpretation of medical images or data.

4. Adjudication Method

Not applicable for this device type. Adjudication methods like 2+1 or 3+1 are used in studies involving human interpretation or labeling of data, typically for AI/ML device validation.

5. Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study

No. An MRMC study is not mentioned because this device is a physical vial access device, not an AI/ML diagnostic or assistive tool for human readers.

6. Standalone Performance Study (Algorithm Only)

No. This is a physical device, not an algorithm.

7. Type of Ground Truth Used

The "ground truth" for this device's evaluation is based on established engineering and biocompatibility standards, and physical performance measurements.

Bench Testing: Objective measurements against documented specifications for leak rates, particulate generation, flow rates, residual volumes, connector compatibility, and package integrity.
Biocompatibility Testing: Results from established in-vitro and in-vivo tests (e.g., cytotoxicity, sensitization, systemic toxicity, hemolysis) against defined biological safety endpoints as per ISO 10993-1.
Sterility Validation: Demonstration of a Sterility Assurance Level (SAL) of 10-6 in accordance with ISO 11137 (for gamma radiation) or ISO 11135 (for ethylene oxide).
Pyrogenicity: Testing to confirm the device is non-pyrogenic.

8. Sample Size for the Training Set

Not applicable. This is a physical medical device, not an AI/ML algorithm that requires a "training set" of data.

9. How the Ground Truth for the Training Set Was Established

Not applicable, as there is no "training set" for this device.

Summary

FDA 510(k) Clearance Letter - HyHub™ and HyHub™ Duo Vial Access Devices

Page 1

U.S. Food & Drug Administration
10903 New Hampshire Avenue
Silver Spring, MD 20993
www.fda.gov

Doc ID # 04017.08.00

July 18, 2025

Takeda Pharmaceuticals
Avanti Sawant
Associate Director Global Regulatory Affairs, Device PDT
500 Kendall Street
Cambridge, Massachusetts 02142

Re: K243404
Trade/Device Name: HyHub™ and HyHub™ Duo Vial Access Devices
Regulation Number: 21 CFR 880.5440
Regulation Name: Intravascular Administration Set
Regulatory Class: Class II
Product Code: LHI
Dated: June 20, 2025
Received: June 20, 2025

Dear Avanti Sawant:

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 (the 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 aware that some cleared products may instead be combination products. The 510(k) Premarket Notification Database available 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.

Additional information about changes that may require a new premarket notification are provided in the FDA guidance documents entitled "Deciding When to Submit a 510(k) for a Change to an Existing Device"

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K243404 - Avanti Sawant Page 2

(https://www.fda.gov/media/99812/download) and "Deciding When to Submit a 510(k) for a Software Change to an Existing Device" (https://www.fda.gov/media/99785/download).

Your device is also subject to, among other requirements, the Quality System (QS) regulation (21 CFR Part 820), which includes, but is not limited to, 21 CFR 820.30, Design controls; 21 CFR 820.90, Nonconforming product; and 21 CFR 820.100, Corrective and preventive action. Please note that regardless of whether a change requires premarket review, the QS regulation requires device manufacturers to review and approve changes to device design and production (21 CFR 820.30 and 21 CFR 820.70) and document changes and approvals in the device master record (21 CFR 820.181).

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-related adverse events) (21 CFR Part 803) for devices or postmarketing safety reporting (21 CFR Part 4, Subpart B) for combination products (see https://www.fda.gov/combination-products/guidance-regulatory-information/postmarketing-safety-reporting-combination-products); good manufacturing practice requirements as set forth in the quality systems (QS) regulation (21 CFR Part 820) for devices or current good manufacturing practices (21 CFR Part 4, Subpart A) for combination products; and, if applicable, the electronic product radiation control provisions (Sections 531-542 of the Act); 21 CFR Parts 1000-1050.

All medical devices, including Class I and unclassified devices and combination product device constituent parts are required to be in compliance with the final Unique Device Identification System rule ("UDI Rule"). The UDI Rule requires, among other things, that a device bear a unique device identifier (UDI) on its label and package (21 CFR 801.20(a)) unless an exception or alternative applies (21 CFR 801.20(b)) and that the dates on the device label be formatted in accordance with 21 CFR 801.18. The UDI Rule (21 CFR 830.300(a) and 830.320(b)) also requires that certain information be submitted to the Global Unique Device Identification Database (GUDID) (21 CFR Part 830 Subpart E). For additional information on these requirements, please see the UDI System webpage at https://www.fda.gov/medical-devices/device-advice-comprehensive-regulatory-assistance/unique-device-identification-system-udi-system.

Also, please note the regulation entitled, "Misbranding by reference to premarket notification" (21 CFR 807.97). For questions regarding the reporting of adverse events under the MDR regulation (21 CFR Part 803), please go to https://www.fda.gov/medical-devices/medical-device-safety/medical-device-reporting-mdr-how-report-medical-device-problems.

For comprehensive regulatory information about medical devices and radiation-emitting products, including information about labeling regulations, please see Device Advice (https://www.fda.gov/medical-devices/device-advice-comprehensive-regulatory-assistance) and CDRH Learn (https://www.fda.gov/training-and-continuing-education/cdrh-learn). 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 (https://www.fda.gov/medical-devices/device-advice-comprehensive-regulatory-assistance/contact-us-division-industry-and-consumer-education-dice) for more information or contact DICE by email (DICE@fda.hhs.gov) or phone (1-800-638-2041 or 301-796-7100).

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K243404 - Avanti Sawant Page 3

Sincerely,

David Wolloscheck -S

David Wolloscheck, Ph.D.
Assistant Director
DHT3C: Division of Drug Delivery and
General Hospital Devices, and
Human Factors
OHT3: Office of Gastrorenal, ObGyn,
General Hospital, and Urology Devices
Office of Product Evaluation and Quality
Center for Devices and Radiological Health

Enclosure

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FORM FDA 3881 (8/23) Page 1 of 1 PSC Publishing Services (301) 443-6740 EF

DEPARTMENT OF HEALTH AND HUMAN SERVICES
Food and Drug Administration

Indications for Use

Form Approved: OMB No. 0910-0120
Expiration Date: 07/31/2026
See PRA Statement below.

510(k) Number (if known): K243404

Device Name: HyHub™ and HyHub™ Duo Vial Access Device

Indications for Use (Describe):
HyHub™ and HyHub™ Duo vial access devices are indicated for patients 17 years of age or older to allow a drug to be transferred from vials without using a needle, as prescribed, in a home environment or clinical setting.

Type of Use (Select one or both, as applicable):
☒ Prescription Use (Part 21 CFR 801 Subpart D)
☐ Over-The-Counter Use (21 CFR 801 Subpart C)

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:

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K243404 – 510(K) SUMMARY

DATE SUBMITTED
18 Jul 2025

Submitter
Takeda Pharmaceuticals U.S.A., Inc.
500 Kendall Street
Cambridge, MA 02142

Contact
Avanti Sawant
Associate Director Global Regulatory Affairs CMC & Device PDT
Avanti.sawant@takeda.com
617-943-1107

Device Information
Trade name: HYHUB™ and HYHUB™ DUO Vial Access Devices
Configurations: Vial Access Device with 2 docking stations
Vial Access Device with 4 docking stations
Common Name: I.V. Fluid Transfer Set
Classification Regulation: 880.5440
Classification Name: Intravascular administration set
Device Classification: Class II
Product Code: LHI

Predicate Device
Trade Name: Fleboset MULTIPLE
510K#: K040456
Product Code: LHI
Manufacturer: LABORATORIOS GRIFOLS, S.A.

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Device Description Summary

Environment of Use

The HYHUB™ and HYHUB™ DUO vial access devices are used in clinical and home environments.

Indications for Use

HYHUB™ and HYHUB™ DUO vial access devices are indicated for patients 17 years of age or older to allow a drug to be transferred from vials without using a needle, as prescribed, in a home environment or clinical setting.

Summary of Technological Characteristics

The following technological characteristic of the HYHUB™ and HYHUB™ DUO vial access devices are substantially equivalent to those of the Predicate, Fleboset MULTIPLE:

Use of a spike to pierce vials and withdraw drug product(s).
Multiple spikes connected in series with flexible tubing segments.
Spike "vent" function facilitated by hydrophobic air filter allowing for withdrawal from vial without having to inject air.
Enables continuous delivery of drug product(s) from multiple source containers.
Can be used in conjunction with an infusion pump.

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Summary of Comparison with Predicate Device

Characteristics	HYHUB™ and HYHUB™ DUO Vial Access Device	Fleboset Multiple	Comparison
Indications for Use	HYHUB™ and HYHUB™ DUO vial access devices are indicated for patients 17 years of age or older to allow a drug to be transferred from vials without using a needle, as prescribed, in a home environment or clinical setting.	Fleboset Multiple is an ancillary device used as fluid pathway through which substances from six glass source flasks containing the same solution may be continuously delivered for I.V. administration when used in conjunction with a gravity or pump infusion set to channel the solution from the source containers to the infusion set.	Same
Sterilization Method	Gamma Radiation Validation per ISO-11137	Ethylene Oxide Validation per ISO-11135	Different

Discussion: Both predicate and subject devices were validated to the sterility assurance levels of 10-6. The results demonstrated that the differences do not raise any new questions of safety and effectiveness for the subject device.

| Spike | Yes | Yes | Same |
| Fluid Path | Two | One | Different |

Discussion: The predicate device contains six (6) spikes connected in series with flexible tubing segments, made up of Polyvinyl Chloride (PVC). Similarly, the subject device has two separate fluid paths which contain spikes connected in series with tubing segments, made of PVC (non-DEHP). The subject device fluid paths have undergone flow testing, residual volume testing and biocompatibility testing to support the intended use. The results demonstrated that the differences do not raise any new questions of safety and effectiveness for the subject device.

Discussion: The predicate device allows withdrawal of drug product from six (6) source containers simultaneously. The subject device allows withdrawal of the drug product from up to two (2) or four (4) source containers simultaneously. Both predicate and subject device can be connected to an infusion pump. Pump compatibility with the VAD was assessed via flow testing and residual volume testing to support the intended use. The results demonstrated that the differences do not raise any new questions of safety and effectiveness for the subject device.

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Performance Bench Testing Summary

The following bench tests were performed in accordance with applicable FDA-recognized standards or internally validated protocols guided by a risk management process:

Leak test
Particulate test
Luer connectors compatibility
Stopper fragmentation test
Sterile packaging test
Flow test
Residual/Injectable Volume test
Human Factors Validation

Biocompatibility Testing Summary

Biocompatibility evaluation was conducted in accordance with ISO 10993-1, considering the device's classification (externally communicating, blood path indirect, with prolonged exposure duration (>24 h to 30 d)). The following endpoints were assessed:

Cytotoxicity
Sensitization
Intracutaneous reactivity
Material mediated pyrogenicity
Acute systemic toxicity
Subacute Toxicity (Dual Route Repeated Exposure)
Hemolysis test
Chemical Characterization
Drug Compatibility

Conclusions

Based upon the comparison of the labeling, the technological and functional characteristics, the information provided in this submission – including results from risk assessments and testing activities related to verification, validation, performance, and usability/human factors – demonstrates that the VAD device functions as intended and is substantially equivalent to the predicate device. Therefore, Takeda concludes that the subject device, VAD, is substantially equivalent to the predicate device (K040456).

Regulation Number and Section

§ 880.5440 Intravascular administration set.

(a)
Identification. An intravascular administration set is a device used to administer fluids from a container to a patient's vascular system through a needle or catheter inserted into a vein. The device may include the needle or catheter, tubing, a flow regulator, a drip chamber, an infusion line filter, an I.V. set stopcock, fluid delivery tubing, connectors between parts of the set, a side tube with a cap to serve as an injection site, and a hollow spike to penetrate and connect the tubing to an I.V. bag or other infusion fluid container.(b)
Classification. Class II (special controls). The special control for pharmacy compounding systems within this classification is the FDA guidance document entitled “Class II Special Controls Guidance Document: Pharmacy Compounding Systems; Final Guidance for Industry and FDA Reviewers.” Pharmacy compounding systems classified within the intravascular administration set are exempt from the premarket notification procedures in subpart E of this part and subject to the limitations in § 880.9.