The HBiofluids HMB32 is a bicarbonate based dialysis solution packaged in a ready to mix, sterile, non-pyrogenic, two-chambered solution container system. One chamber contains the acidic solution and one chamber contains the basic solution. At the point of use, the membrane between the two chambers is broken, and the acidic and basic solutions are mixed to form the final ionic composition of the solution to be used in the Continuous Renal Replacement Therapy (CRRT) treatment.

The HBiofluids HMB32 solution will be offered in one formulation, in two different volumes: 500+4500 ml and 500+1500 ml.

AI/ML Overview

The provided text describes the HBiofluids HMB32 dialysis solution and its substantial equivalence to a predicate device (Accusol, K041428) for use in Continuous Renal Replacement Therapy. This is a medical device submission based on substantial equivalence, not typically one that relies on clinical performance studies with specific accuracy metrics in the way AI/ML devices do. Therefore, many of the questions regarding acceptance criteria, sample sizes for test/training sets, expert adjudication, MRMC studies, or standalone algorithm performance are not applicable to this type of submission.

However, I can extract information related to the device's characteristics and the nonclinical testing performed to establish its safety and effectiveness.

Here's a breakdown of the available information:

1. Table of Acceptance Criteria and Reported Device Performance:

Since this is a submission for a dialysis solution based on substantial equivalence, the "acceptance criteria" are primarily established by demonstrating similarity to a legally marketed predicate device and meeting relevant standards for manufacturing, biocompatibility, and sterility. There are no specific performance metrics like sensitivity, specificity, or AUC that would be generated from a clinical study for this type of device.

Instead, the comparison focuses on key parameters and chemical composition.

Parameter	Predicate Device (ACCUSOL, K041428)	HMB32 (Reported Performance)	Acceptance/Comparison Outcome
Indication for Use	For use as a dialysis solution in continuous renal replacement therapy	For use as a dialysis solution in continuous renal replacement therapy	Substantially Equivalent
Overall Design	Two units of 5 liter double chamber non-PVC bags, over-wrapped, clear/colorless solution	Two units of 5 liter or four units of 2 liter double chamber PVC free bags, over-wrapped, clear/colorless solution	Similar/Equivalent (PVC free noted for HMB32)
Ionic Composition of Final Solution (mmol/l):			Acceptance is based on close numerical values and clinical equivalence for use as a dialysis solution.
Na+	140.00	140.00	Match
K+	2.00	2.50	Close/Clinical Equivalence
Ca++	1.75	1.50	Close/Clinical Equivalence
Mg++	0.50	0.75	Close/Clinical Equivalence
HCO3-	35.00	32.00	Close/Clinical Equivalence
Cl-	111.30	115.00	Close/Clinical Equivalence
Glucose	5.55	5.55	Match
Theoretical Osmolarity	296 mOsm/l	297 mOsm/l	Close/Clinical Equivalence
Solution container components and materials	Two chamber container system, administration site with membrane tube and pull-ring closure, medication port	Two chamber container system, administration tube with luer lock, second tube for optional insertion	Similar functionality and design logic
Biocompatibility of patient contacting container/closure components	Established via testing per ISO 10993-1	Established via testing per ISO 10993-1	Same standard, assumed equivalent
Sterilization	Moist heat	Moist heat	Match
Shelf life	12 months	12 months	Match
Additional Nonclinical Testing	(Not detailed for predicate)		Acceptance based on meeting standards.
- Biocompatibility	N/A (but similar standard)	Components found in human plasma, complies with European Pharmacopeia 8.0. Materials of container/closure system are medical grade, meet ISO 10993-1 and USP Class VI.	Met standards (ISO 10993-1, USP Class VI, EP 8.0)
- Sterilization Validation	N/A (but "moist heat")	Steam sterilization validated to SAL of 10^-6 per EN ISO 17665-1:2007	Validated (EN ISO 17665-1)
- Pyrogenicity Testing	N/A	LAL test confirmed non-pyrogenic	Confirmed non-pyrogenic
- Stability Testing	N/A (but "12 months")	Real-time aging out to 18 months confirmed integrity, labeled with 12-month shelf life.	Confirmed (18-month stability for 12-month shelf life)

2. Sample size used for the test set and the data provenance:

Sample Size for Test Set: Not applicable. This device is a dialysis solution, and its performance is evaluated primarily through chemical composition analysis, material testing (biocompatibility, sterility), and stability studies, rather than a "test set" of patient data or images.
Data Provenance: Not applicable in the context of clinical "data" for a test set. The validation is based on laboratory testing of the solution and its components, and comparison to the predicate device's established characteristics.

3. Number of experts used to establish the ground truth for the test set and the qualifications of those experts:

Not applicable. There is no concept of "ground truth" derived from expert consensus in the context of chemical composition, sterility, or biocompatibility testing for a dialysis solution.

4. Adjudication method (e.g., 2+1, 3+1, none) for the test set:

Not applicable.

5. 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 not an AI/ML diagnostic or therapeutic device.

6. If a standalone (i.e. algorithm only without human-in-the loop performance) was done:

Not applicable.

7. The type of ground truth used (expert consensus, pathology, outcomes data, etc.):

Not applicable in the conventional sense. The "ground truth" for this device's safety and effectiveness is established by:
- Chemical Analysis: Direct measurement of ionic composition and osmolarity.
- International Standards: Compliance with ISO 10993-1, USP Class VI, European Pharmacopeia 8.0, and EN ISO 17665-1 for biocompatibility, material safety, and sterilization.
- Material Science: Testing of container/closure materials.
- Stability Studies: Experimental data from real-time aging.

8. The sample size for the training set:

Not applicable. This device does not use machine learning, so there is no training set.

9. How the ground truth for the training set was established:

Not applicable.

Summary

{0}------------------------------------------------

Image /page/0/Picture/1 description: The image shows the logo for the U.S. Department of Health & Human Services. The logo consists of a circular seal with the text "DEPARTMENT OF HEALTH & HUMAN SERVICES - USA" arranged around the perimeter. Inside the circle is a stylized image of three faces in profile, stacked one behind the other, representing the department's focus on people and health.

Food and Drug Administration 10903 New Hampshire Avenue Document Control Center - WO66-G609 Silver Spring, MD 20993-0002

December 4, 2015

Haemopharm Biofluids Srl (HBiofluids) % Sheila Hemeon-Heyer President Heyer Regulatory Solutions, LLC P.O. Box 2151 Amherst, MA 01004-2151

Re: K150966

Trade/Device Name: HMB32 500 + 4500 ml and 500 + 1500 ml Regulation Number: 21 CFR§ 876.5820 Regulation Name: Hemodialysis system and accessories Regulatory Class: II Product Code: KPO Dated: October 29, 2015 Received: October 29, 2015

Dear Sheila Hemeon-Heyer,

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.

{1}------------------------------------------------

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 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 go to http://www.fda.gov/AboutFDA/CentersOffices/CDRH/CDRHOffices/ucm115809.htm for the Center for Devices and Radiological Health's (CDRH's) Office of Compliance. Also, please note the regulation entitled, "Misbranding by reference to premarket notification" (21CFR 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 Small Manufacturers, International and Consumer Assistance at its toll-free number (800) 638-2041 or (301) 796-7100 or at its Internet address http://www.fda.gov/MedicalDevices/ResourcesforYou/Industry/default.htm.

Sincerely vours.

Benjamin R. Fisher -S

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)

K150966

Device Name

HMB32 500 + 4500 ml and 500 + 1500 ml

Indications for Use (Describe)

Intended for use as a dialysis solution in Continuous Renal Replacement Therapy.

Type of Use (Select one or both, as applicable)	☑ Research Use Only (21 CFR 201.128 Subject to 501(b))☐ For In-Vitro Use Only (21 CFR 201.128 Subject to 501(b))	☑ Research Use Only (21 CFR 201.128 Subject to 501(b))	☐ For In-Vitro Use Only (21 CFR 201.128 Subject to 501(b))
☑ Research Use Only (21 CFR 201.128 Subject to 501(b))	☐ For In-Vitro Use Only (21 CFR 201.128 Subject to 501(b))

X 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:

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

1. SUBMITTER:	Haemopharm Biofluids srlVia dell'Industria 623030 Tovo S. AgataSondrio, Italy
2. CONTACT PERSON:	Giuseppe TomasiniPhone: 011 39 0535 29323Mobile: 011 39 3355733390Fax: 011 39 0535 29177
3. DATE PREPARED:	April 10, 2015
4. DEVICE TRADE NAME:MODEL NUMBERS:	HMB32(500 + 4500 ml) and (500 + 1500 ml)
5. COMMON NAME:CLASSIFICATION NAME:	Haemofiltration and Dialysis SolutionDialysate Concentrate for Hemodialysis(Liquid or Powder)
6. CLASSIFICATION:	21 CFR 876.5820, Product Code KPOClass II
7. PREDICATE DEVICE(S):	K041428, Accusol Dialysis Solutions, BaxterHealthcare

8. DEVICE DESCRIPTION:

The HBiofluids HMB32 solution will be offered in one formulation, in two different volumes: 500+4500 ml and 500+1500 ml. The chemical compositions of the final solutions for these two volumes are shown in the substantial equivalence table below.

{4}------------------------------------------------

9. INDICATION FOR USE:

Intended for use as a dialysis solution in Continuous Renal Replacement Therapy.

10. COMPARISON TO PREDICATE DEVICE:

The table below provides a technical comparison to the predicate device. There are no significant differences between the HBiofluids HMB32 solution as compared to the predicate Accusol solution.

Parameter	Predicate DeviceACCUSOL, K041428	HMB32
Indication for use	For use as a dialysissolution in continuousrenal replacementtherapy	For use as a dialysissolution in continuousrenal replacementtherapy
Overall design	The solution is suppliedin a carton boxcontaining two units of 5liter double chambernon-PVC bags.Each bag is over-wrapped in itsoverpouch.The solution in the bagis clear and colorless.	The solution is suppliedin a carton boxcontaining two units of5 liter or four units of 2liter double chamberPVC free bags.Each bag is over-wrapped in itsoverpouch.The solution in the bagis clear and colorless.
lonic compositionof final solution(mmol/l):
Na+	140.00	140.00
K+	2.00	2.50
Ca++	1.75	1.50
Mg++	0.50	0.75
HCO3-	35.00	32.00
Cl-	111.30	115.00
Glucose	5.55	5.55
Theoreticalosmolarity	296 mOsm/l	297 mOsm/l
Solution containercomponents andmaterials	Supplied in a twochamber containersystem. At the time ofuse, the contents of thetwo chambers are mixedtogether creating the	Supplied in a twochamber containersystem. At the time ofuse, the contents of thetwo chambers aremixed together creating

{5}------------------------------------------------

Parameter	Predicate DeviceACCUSOL, K041428	HMB32
	dialysate solution. Themixed solution isdelivered to thedialysate pathway of theblood tubing paththrough theadministration siteconsisting of amembrane tube and apull-ring closure andconnected to the bottomchamber. A medicationport is provided foroptional insertion ofother substances intothe mixed solution priorto use.	the dialysate solution.The mixed solution isdelivered to thedialysate pathway ofthe blood tubing paththrough theadministration tubeconnected to thebottom chamber, whichis opened and closedusing a luer lock. Asecond tube in the largechamber can be usedfor optional insertion ofother substances intothe mixed solution priorto use.
Biocompatibilityof patientcontactingcontainer/closurecomponents	Established via testingper ISO 10993-1	Established via testingper ISO 10993-1
Sterilization	moist heat	moist heat
Shelf life	12 months	12 months

11. NONCLINICAL TESTING:

Biocompatibility: The HMB32 solution consists of components found in human plasma and is in compliance with the European Pharmacopeia 8.0, "Haemofiltration and haemodiafiltration, solution for," current edition 07/2013:0861. The materials of the container/closure system come into contact with the solution, but do not come into direct contact with the patient. Biological assessments are provided to demonstrate that the materials in contact with the solution are medical grade, meet ISO 10993-1 and USP Class VI plastics requirements, and are commonly used for medical devices and injectable pharmaceuticals.

Sterilization Validation: The steam sterilization method was validated to an SAL of 10° in accordance with EN ISO 17665-1: 2007 Sterilization of health care products - Moist heat - Part 1: Requirements for the development, validation and routine control of sterilization process for medical devices.

Pyrogenicity testing conducted using the LAL test confirmed that the solution is not pyrogenic.

{6}------------------------------------------------

Stability testing conducted after real-time aging out to 18 months confirmed the integrity of both the solution and the container/closure system. The HMB32 product will be labeled with a 12 month shelf life.

12. CONCLUSION:

The information and testing presented in this 510(k) demonstrates that the HBiofluids HMB32 is safe and effective for use during Continuous Renal Replacement Therapy as demonstrated by confirmation of substantial equivalence to the Accusol dialysis solution cleared under K041428.

Regulation Number and Section

§ 876.5820 Hemodialysis system and accessories.

(a)
Identification. A hemodialysis system and accessories is a device that is used as an artificial kidney system for the treatment of patients with renal failure or toxemic conditions and that consists of an extracorporeal blood system, a conventional dialyzer, a dialysate delivery system, and accessories. Blood from a patient flows through the tubing of the extracorporeal blood system and accessories to the blood compartment of the dialyzer, then returns through further tubing of the extracorporeal blood system to the patient. The dialyzer has two compartments that are separated by a semipermeable membrane. While the blood is in the blood compartment, undesirable substances in the blood pass through the semipermeable membrane into the dialysate in the dialysate compartment. The dialysate delivery system controls and monitors the dialysate circulating through the dialysate compartment of the dialyzer.(1) The extracorporeal blood system and accessories consists of tubing, pumps, pressure monitors, air foam or bubble detectors, and alarms to keep blood moving safely from the blood access device and accessories for hemodialysis (§ 876.5540) to the blood compartment of the dialyzer and back to the patient.
(2) The conventional dialyzer allows a transfer of water and solutes between the blood and the dialysate through the semipermeable membrane. The semipermeable membrane of the conventional dialyzer has a sufficiently low permeability to water that an ultrafiltration controller is not required to prevent excessive loss of water from the patient's blood. This conventional dialyzer does not include hemodialyzers with the disposable inserts (Kiil type) (§ 876.5830) or dialyzers of high permeability (§ 876.5860).
(3) The dialysate delivery system consists of mechanisms that monitor and control the temperature, conductivity, flow rate, and pressure of the dialysate and circulates dialysate through the dialysate compartment of the dialyzer. The dialysate delivery system includes the dialysate concentrate for hemodialysis (liquid or powder) and alarms to indicate abnormal dialysate conditions. This dialysate delivery system does not include the sorbent regenerated dialysate delivery system for hemodialysis (§ 876.5600), the dialysate delivery system of the peritoneal dialysis system and accessories (§ 876.5630), or the controlled dialysate delivery system of the high permeability hemodialysis system § 876.5860).
(4) Remote accessories to the hemodialysis system include the unpowered dialysis chair without a scale, the powered dialysis chair without a scale, the dialyzer holder set, dialysis tie gun and ties, and hemodialysis start/stop tray.
(b)
Classification. (1) Class II (performance standards) for hemodialysis systems and all accessories directly associated with the extracorporeal blood system and the dialysate delivery system.(2) Class I for other accessories of the hemodialysis system remote from the extracorporeal blood system and the dialysate delivery system, such as the unpowered dialysis chair, hemodialysis start/stop tray, dialyzer holder set, and dialysis tie gun and ties. The devices subject to this paragraph (b)(2) are exempt from the premarket notification procedures in subpart E of part 807 of this chapter subject to the limitations in § 876.9.