The BEL-GEN Cold Storage Solution is intended for the flushing and the hypothermic storage of kidney, liver and pancreas organs at the time of organ removal from the donor in preparation for storage, transportation and eventual transplantation into a recipient.

Device Description

Institut Georges Lopez manufactures the BEL-GEN Cold Storage Solution according to the solution pioneered at the University of Wisconsin by Dr Folkert O. Belzer, often referred to as "Belzer UW solution". The formulation includes soluble colloids, buffers, sodium and potassium salts, redox stabilizers, and phosphoric compounds to aid tissue viability by enabling regeneration of adenosine triphosphate (ATP).

The BEL-GEN Cold Storage Solution is a clear to light yellow single use, sterile and non-pyrogenic solution. BEL-GEN Cold Storage Solution has an osmolality of 320 mOsm/kg, a total sodium concentration of 29 mmol/L, a total potassium concentration of 125 mmol/L and a pH of 7.4 at room temperature. The solution is packaged in 1-liter or 2-liter bags with a shelf life of 2 years.

The BEL-GEN Cold Storage solution is used at hospital by health professionals. The BEL-GEN Cold Storage solution must be cooled to +2°C (36° and 43°F) prior to use The cold solution is used to flush the isolated organ immediately before removal from the donor and/or immediately after removal from the donor. The solution is then left in the organ vasculature during hypothermic storage and transportation to cool the organ and lower its metabolic requirements.

AI/ML Overview

The provided text is a 510(k) Premarket Notification for a medical device called "BEL-GEN Cold Storage Solution." This document focuses on demonstrating that the device is substantially equivalent to existing predicate devices, rather than proving its efficacy through a clinical study with specific acceptance criteria related to a new function or performance benefit.

Therefore, many of the requested details about acceptance criteria, study design for device performance, expert involvement, and ground truth establishment are not directly applicable or present in this type of regulatory submission. The submission is primarily about proving manufacturing quality, safety, and equivalence to a known product.

Here's an analysis based on the provided document, addressing the points where information is available and indicating where it is not:

1. A table of acceptance criteria and the reported device performance

The document does not present "acceptance criteria" in the traditional sense of a clinical trial with performance metrics. Instead, it demonstrates through non-clinical testing that the device meets established safety and quality standards and retains its properties over its shelf life, showing equivalence to predicate devices.

Acceptance Criteria (Equivalent to Performance Standards and Safety)	Reported Device Performance
Device Characteristics (for Substantial Equivalence Comparison):
- Intended Use/Indications for Use: Intended for flushing and hypothermic storage of kidney, liver, and pancreas organs for transplantation.	- Same: The BEL-GEN Cold Storage Solution has the same intended use as the predicate devices.
- Principle of Operation: Based on the "Belzer UW solution" enabling regeneration of ATP to aid tissue viability.	- Same: Functions similarly by cooling the organ and lowering its metabolic requirements.
- Chemical Composition: Similar to predicate devices, based on Belzer UW solution (Pentafraction (HES), Lactobionic acid, Potassium Phosphate monobasic, Magnesium Sulfate heptahydrate, Raffinose pentahydrate, Adenosine, Allopurinol, Glutathione, Potassium Hydroxide, Sodium Hydroxide).	- Similar: Same composition as secondary predicate. Slight difference from primary predicate regarding HCl (not necessary to adjust pH 7.4 in subject device).
- pH at Room Temperature: 7.4	- 7.4: Matches predicate devices.
- Osmolality: 320 mOsm/Kg	- 320 mOsm/Kg: Matches predicate devices.
- Sterility: Sterile solution.	- Sterile: Validated through sterilizing filtration and aseptic filling process according to ISO 13408-1 and ISO 13408-2.
- Non-Pyrogenic: Non-pyrogenic solution.	- Non-Pyrogenic: Demonstrated.
- Single Use: Yes.	- Yes: Matches predicate devices.
- Biomaterial Safety: Safe for intended biocontact.	- Safe: Evaluated through ISO 10993 compliant testing (cytotoxicity, skin sensitization, primary skin irritation, hemolysis, acute systemic toxicity) with favorable results.
- Shelf Life Stability: Maintain product specifications for the labeled shelf life.	- 24 months (2 years): Stability testing showed aging at recommended storage conditions (2-25°C) does not affect product specifications for a 2-year shelf life. This is an extension from the primary predicate (1 year) but matches the secondary predicate.
- Dispensing Bag Material and Design: EVA as fluid contact layer, with 3 tubing connections (ports).	- Same: Matches predicate devices.
- Format: 1-liter and 2-liter bags.	- Added 2-liter format: Primary predicate was 1-liter only. This is an addition to the existing format.
- Storage Condition: Room temperature (2-25°C).	- 2-25°C: Matches secondary predicate. This is an extension from the primary predicate (2-8°C).
- Pre-use Conditions: Cool at 2-6°C prior to use.	- Same: Matches predicate devices.

2. Sample sized used for the test set and the data provenance (e.g. country of origin of the data, retrospective or prospective)

This submission describes non-clinical testing (e.g., sterilization validation, biomaterial safety, stability testing) rather than a clinical study involving human or animal subjects for assessing device performance on organs. Therefore, concepts like "test set sample size" for a clinical trial are not applicable here.

Sample Size: Not specified in terms of clinical cases, but standard testing methodologies for sterilization, biocompatibility, and stability would have defined sample sizes for their respective tests (e.g., number of bags tested for sterility, number of animals for toxicity tests, number of solution samples for stability). These specific numbers are not detailed in the summary.
Data Provenance: The manufacturer is Institut Georges Lopez (IGL) based in Lissieu, France. The tests were performed to current industry standards (ISO). The testing is prospective for the purpose of this submission (i.e., new tests performed to support the 510(k)).

3. Number of experts used to establish the ground truth for the test set and the qualifications of those experts (e.g. radiologist with 10 years of experience)

This is not applicable as there is no "ground truth" established by experts in the context of clinical performance or diagnosis for this type of submission. The tests performed are laboratory-based (e.g., chemical analysis, microbiological testing, in-vitro/in-vivo biocompatibility assays, stability testing). "Ground truth" in this context refers to the defined results of these standardized tests against established parameters (e.g., a solution is sterile if no microbial growth is detected).

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

Not applicable. This is not a study assessing human reader performance or diagnostic accuracy.

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 is a premarket notification for a medical solution, not an AI/CADe/CADx device that assists human readers.

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

Not applicable. This is a cold storage solution, not an algorithm.

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

As mentioned in point 3, the "ground truth" refers to the scientific and regulatory standards met by the physical and chemical properties of the solution and its packaging, and its biological safety. This is based on:

Chemical composition, pH, osmolality: Verified by analytical chemistry methods to conform to the established formulation (Belzer UW solution).
Sterility: Absence of microbial contamination, verified by microbiology testing (e.g., sterility tests).
Non-pyrogenicity: Absence of fever-inducing substances, verified by pyrogen testing.
Biocompatibility: Absence of toxic or adverse reactions, verified by ISO 10993 compliant in-vitro and in-vivo tests.
Stability: Maintenance of critical parameters over time, verified by accelerated and real-time aging studies.

These are objective, laboratory-determined "truths" against scientific definitions and regulatory thresholds, not subjective expert consensus.

8. The sample size for the training set

Not applicable. This is not a machine learning or AI device that requires a training set. The device is a chemical solution.

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

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

Summary

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June 14, 2022

Institut Georges Lopez Matthieu Prouteau Director of Quality Affairs and Regulatory Affairs Parc Tertiaire du Bois Dieu RN 6 - 1 Allee des Chevreuils Lissieu. 69380 France

Re: K221387

Trade/Device Name: BEL-GEN Cold Storage Solution Regulation Number: 21 CFR 876.5880 Regulation Name: Isolated kidney perfusion and transport system and accessories Regulatory Class: Class II Product Code: KDL Dated: May 6, 2022 Received: May 13, 2022

Dear Matthieu Prouteau:

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 aware 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.

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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/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 4, Subpart A) for combination products; and, if applicable, the electronic product radiation control provisions (Sections 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 https://www.fda.gov/medical-device-safety/medical-device-reportingmdr-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/medicaldevices/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-device-advice-comprehensive-regulatoryassistance/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).

Sincerely.

Gema Gonzalez Acting Assistant Director DHT3A: Division of Renal, Gastrointestinal, Obesity and Transplant Devices OHT3: Office of GastroRenal, ObGyn, General Hospital and Urology Devices Office of Product Evaluation and Ouality Center for Devices and Radiological Health

Enclosure

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Indications for Use

510(k) Number (if known) K221387

Device Name BEL-GEN Cold Storage Solution

Indications for Use (Describe)

Type of Use (Select one or both, as applicable)	Repackaging Use (Part 21 CFR 201.2 Subject to Phase I) Over-The-Counter Use (21 CFR 201.2 Subject to Phase I)	Repackaging Use (Part 21 CFR 201.2 Subject to Phase I)	Over-The-Counter Use (21 CFR 201.2 Subject to Phase I)
Repackaging Use (Part 21 CFR 201.2 Subject to Phase I)	Over-The-Counter Use (21 CFR 201.2 Subject to Phase I)

Prescription Use (Part 21 CFR 801 Subpart D)

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

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K221387 Page 1 of 5

Traditional 510(k) Premarket Notification BEL-GEN Cold Storage Solution

510(k) Summary

[As Required by 21 CFR 807.92]

Written on June, 14 2022

I. Submitter:

Institut Georges Lopez (IGL) Parc Tertiaire du Bois Dieu RN6 - 1 allée des Chevreuils 69380 Lissieu France Telephone: +33 437 646 332 Official Contact: Matthieu Prouteau - Director of Quality and Regulatory Affairs

II. Device Information

Trade Name:	BEL-GEN Cold Storage Solution
Common Name:	Cold Storage Solution
Regulation Description:	Isolated kidney perfusion and transport system and accessories
Regulation Number:	21 CFR 876.5880
Class:	Class II
Product Code:	KDL, KDN

III. Predicate Device Identification

Primary predicate: BEL-GEN Cold Storage Solution - Waters Instruments, Inc. - K121618 Secondary predicate: CoStorSol® - Preservation Solution Inc. - K091245

IV. Device Description

Confidential

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K221387 Page 2 of 5

Traditional 510(k) Premarket Notification BEL-GEN Cold Storage Solution

V. Indications for Use

VI. Comparison of Technological Characteristics

The BEL-GEN Cold Storage Solution received substantial equivalence determination after submission premarket notification (510(k) number K121618). Modified BEL-GEN Cold Storage Solution is an addition of packaging size, an extension of shelf life and storage conditions from the primary predicate.

The subject device BEL-GEN Cold Storage Solution and secondary predicate are labeled as sterile with a 2-year shelf life at 2-25°C whereas the primary predicate solution with a 1 year shelf life at 2-8°C. However, all three Solutions must be cooled to 2-6°C and do not need to be filtered before use.

BEL-GEN Cold Storage Solution is substantially equivalent to primary and secondary predicate devices. The subject device has the same intended use, indication for use and the principle of operation as predicate devices. All three solutions have the same pH, osmolality, and chemical composition based on Belzer UW solution (except for Hydrochloric acid indicated in primary predicate and not necessary to adjust the pH at 7.4).

The subject and the both predicate devices are sterile, single use, non-pyrogenic and transparent solutions. All three solutions are sterilized by filtration and aseptically filled in similar design dispensing bags (3 ports) and made of EVA as fluid contact layer.

The following table provides a comparison of attributes between the subject device and the predicate devices:

	Subject Device	Primary Predicate	Secondary Predicate	Comparison
Device	BEL-GEN ColdStorage Solution	BEL-GEN ColdStorage Solution	CoStorSol®
510(k) Number	K221387	K121618	K091245
Manufacturer	Institut GeorgesLopez,France	Institut GeorgesLopez,France	Preservation Solutions,Inc.WI, USA	NA
Classification& ProductCode	876.5880, KDL, KDN	876.5880, KDL, KDN	876.5880, KDN	Same, except forsecondarypredicate
DeviceClassificationName	Isolated kidneyperfusion and transportsystem and accessories	Isolated kidneyperfusion and transportsystem and accessories	Isolated kidneyperfusion and transportsystem and accessories	Same
DeviceDescription	The BEL-GEN ColdStorage Solution is aclear to light yellow,sterile and non-pyrogenic solution.	The BEL-GEN ColdStorage Solution is aclear to light yellow,sterile and non-pyrogenic solution.	CoStorSol® is a clearto light yellow, sterileand non-pyrogenicsolution.	Same
	Subject Device	Primary Predicate	Secondary Predicate	Comparison
Format	The solution ispackaged in 1-literand 2-liter bags	The solution ispackaged in 1-literbags	The solution ispackaged in 1-literbags	SimilarThe 2-liter formatis added for thesubject device
Intended use	The BEL-GEN ColdStorage Solution isintended for theflushing and thehypothermic storage ofkidney, liver andpancreas organs at thetime of organ removalfrom the donor inpreparation for storage,transportation andeventualtransplantation into arecipient.	The BEL-GEN ColdStorage Solution isintended for theflushing and thehypothermic storage ofkidney, liver andpancreas organs at thetime of organ removalfrom the donor inpreparation for storage,transportation andeventualtransplantation into arecipient.	CoStorSol ® isintended for theflushing and coldstorage of kidney, liverand pancreas organs atthe time of organremoval from thedonor in preparationfor storage,transportation andeventualtransplantation into arecipient	Same
Solution Type	IntracellularNa+ 29 mmol/LK+ 125 mmol/L	IntracellularNa+ 29 mmol/LK+ 125 mmol/L	IntracellularNa+ 29 mmol/LK+ 125 mmol/L	Same
Composition	Pentafraction (HES)(50 g/L) ; Lactobionicacid (35.83 g/L) ;Potassium Phosphatemonobasic (3.4 g/L) ;Magnesium Sulfateheptahydrate (1.23g/L) ; Raffinosepentahydrate(17.83 g/L) ;Adenosine (1.34 g/L)Allopurinol (0.136g/L) ; Glutathione(0.922 g/L) ;Potassium Hydroxide(5.61 g/L) ; SodiumHydroxide (qs pH 7.4)Water for injection (qs1 Litre)	Pentafraction (HES)(50 g/L) ; Lactobionicacid (35.83 g/L) ;Potassium Phosphatemonobasic (3.4 g/L) ;Magnesium Sulfateheptahydrate (1.23g/L) ; Raffinosepentahydrate(17.83 g/L) ;Adenosine (1.34 g/L)Allopurinol (0.136g/L) ; Glutathione(0.922 g/L) ;Potassium Hydroxide(5.61 g/L) ; SodiumHydroxide /Hydrochloric acid (qspH 7.4)Water for injection (qs1 Litre)	Pentafraction (HES)(50 g/L) ; Lactobionicacid (35.83 g/L) ;Potassium Phosphatemonobasic (3.4 g/L) ;Magnesium Sulfateheptahydrate (1.23g/L) ; Raffinosepentahydrate(17.83 g/L) ;Adenosine (1.34 g/L)Allopurinol (0.136g/L) ; Glutathione(0.922 g/L) ;Potassium Hydroxide(5.61 g/L) ; SodiumHydroxide(qs pH 7.4)Water for injection (qs1 Litre)	Same assecondarypredicate.Similar toprimary predicate
pH at roomtemperature	7.4	7.4	7.4	Same
Osmolality	320 mOsm/Kg	320 mOsm/Kg	320 mOsm/Kg	Same
Sterility	Sterile solution	Sterile solution	Sterile solution	Same
SterilizationMethod	Aseptic filtration(sterile A)	Aseptic filtration(sterile A)	Aseptic filtration(sterile A)	Same
Single use	Yes	Yes	Yes	Same
	Subject Device	Primary Predicate	Secondary Predicate	Comparison

Filtrationrequired beforeuse?	No	No	No	Same
Dispensing bag	Dispensing bags aremade of ethylene-vinylacetate (EVA) as fluidcontact layer, with 3tubing connections(ports)	Dispensing bags aremade of ethylene-vinylacetate (EVA) as fluidcontact layer, with 3tubing connections(ports)	Dispensing bags aremade of ethylene-vinylacetate (EVA) as fluidcontact layer, with 3tubing connections(ports)	Same
Shelf life	24 months (2 years)	12 months (1 year)	24 months (2 years)	Same assecondarypredicate.Shelf lifeExtension fromprimary predicate.
StorageCondition	Room temperature (2-25°C)(35.6° - 77°F)	Room temperature (2-8°C)(35.6° - 46.4°F)	Room temperature (2-25°C)(35.6° - 77°F)	Same assecondarypredicate.Storageconditionsextension fromprimary predicate.
Pre-useconditions	Cool at 2-6°C	Cool at 2-6°C	Cool at 2-6°C	Same

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Traditional 510(k) Premarket Notification

Confidential

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Traditional 510(k) Premarket Notification BEL-GEN Cold Storage Solution

VII. Summary of Non-Clinical Testing

No performance standards have been established by FDA for the BEL-GEN Cold Storage Solution.

The following tests were performed to demonstrate safety based on current industry standards:

The BEL-GEN Cold Storage Solution is supplied sterile and non-pyrogenic in order to assure safety for transplant recipients. The validation of the sterilizing filtration and aseptic filling process were carried out according to ISO 13408-1 and ISO 13408-2.
-The biomaterial safety of the BEL-GEN Cold Storage Solution has been evaluated through ISO 10993 compliant testing, which included cytotoxicity test, skin sensitization test in guinea pigs, primary skin irritation, hemolysis test and acute systemic toxicity test in mice. Results of this testing, showed the BEL-GEN Cold Storage Solution is safe for the intended biocontact.
The stability testing has showed that aging of test articles at the recommended storage conditions of 2-25°C (35.6° - 77°F) does not affect the product specifications for the BEL-GEN Cold Storage Solution labeled with 2-year shelf life.

The results of these tests indicate that BEL-GEN Cold Storage Solution is substantially equivalent to the predicate devices.

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Traditional 510(k) Premarket Notification BEL-GEN Cold Storage Solution

VIII. Conclusion

The technological differences between the subject and predicate devices were evaluated through nonclinical testing. The results of these tests demonstrated that the subject device does not raise of safety and effectiveness compared to the predicate devices. The indications for use, technological characteristics, and performance characteristics of BEL-GEN Cold Storage Solution stored for up to 2 years at 2-25°C (35.6° - 77°F) assessed to be substantially equivalent to the predicate devices.

Regulation Number and Section

§ 876.5880 Isolated kidney perfusion and transport system and accessories.

(a)
Identification. An isolated kidney perfusion and transport system and accessories is a device that is used to support a donated or a cadaver kidney and to maintain the organ in a near-normal physiologic state until it is transplanted into a recipient patient. This generic type of device may include tubing, catheters, connectors, an ice storage or freezing container with or without bag or preservatives, pulsatile or nonpulsatile hypothermic isolated organ perfusion apparatus with or without oxygenator, and disposable perfusion set.(b)
Classification. Class II (performance standards).