Celsior™ is intended for flushing and cold storage of a heart at the time of its removal from a donor in preparation for storage, transportation, and eventual transplantation into a recipient.

Device Description

Celsior (SangStat Medical Corporation, Fremont, CA) is a clear to slightly yellow, sterile, non-pyrogenic, extracellular solution for hypothermic flushing and storage of hearts. The solution is slightly acidic (pH 7.3 + 0.10), slightly hypertonic (osmolarity 320-360 mOsmol) with low viscosity (1.15 cSt), and has a high buffering capacity (acidic approximately 11 mmol, alkaline approximately 7 mmol). The composition of Celsior is thus consistent with that of an extracellular solution.

Celsior is filled into 1 liter ethylene-vinyl acetate copolymer (EVA) bags. The EVA bags are sterilized (ethylene oxide) and aseptically filled up to 1,000 mL in a sterile area. After filling, each EVA bag is enveloped by an aluminum protected bag containing an oxygen absorbent sachet. This product must be stored under refrigerated conditions at 2° to 8°C (36° to 46°F) until it is used.

AI/ML Overview

Here's a breakdown of the acceptance criteria and study information for the Celsior™ Cold Storage Solution, based on the provided text:

1. Table of Acceptance Criteria and Reported Device Performance

Acceptance Criteria (Implicit by Predicate Equivalence)	Reported Device Performance (Celsior™)
Primary Efficacy Endpoint: 7-day patient survival comparable to predicate and other standard preservation solutions.	Clinical Studies:
Secondary Efficacy Endpoints: 30-day patient and graft survival comparable to predicate and other standard preservation solutions.	- "The primary efficacy endpoint of seven (7) day patient survival was comparable between groups" (Celsior vs. ViaSpan and other standard preservation solutions).
Safety Endpoints: Similar adverse event profiles to predicate and other standard preservation solutions.	- "as were the secondary endpoints of 30 day patient and graft survival."
	- "In the first 30 days posttransplant, significantly fewer subjects receiving Celsior-treated hearts had one or more cardiac-related serious adverse events based on one-sided 95% confidence interval analysis." (This suggests Celsior may have even better safety in this specific regard).
	- "Clinical studies demonstrated that Celsior and ViaSpan had similar adverse event profiles and that adverse events using Celsior were also similar to that for other hospital solutions currently used to prepare hearts for transplant."
Biocompatibility: Demonstrated biocompatibility (cytotoxicity, intracutaneous, in vitro hemolysis, in vivo hemolysis, osmotic fragility).	Preclinical Studies:
Sterility: Demonstrated sterility following processing.	- "Preclinical studies also demonstrate the biocompatibility (e.g., cytotoxicity, intracutaneous, in vitro hemolysis, in vivo hemolysis, osmotic fragility), sterility (ethylene oxide, ethylene chlorohydrin, and ethylene glycol), and stability of Celsior."
Stability: Demonstrated stability under storage conditions.	- "Preclinical studies also demonstrate the biocompatibility (e.g., cytotoxicity, intracutaneous, in vitro hemolysis, in vivo hemolysis, osmotic fragility), sterility (ethylene oxide, ethylene chlorohydrin, and ethylene glycol), and stability of Celsior."
Preclinical Performance: Performed at least as well as predicate in preclinical models.	- "Preclinical studies conducted in isolated rabbit hearts and mongrel canines demonstrate that Celsior-treated hearts performed better than ViaSpan-treated hearts."

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

Sample Size: Not explicitly stated for the overall clinical trial. The document mentions "subjects receiving Celsior-treated hearts" but does not give a total N.
Data Provenance:
- Country of Origin: The primary clinical study was conducted in the U.S. (IDE file number G970052), described as a "multicenter" trial.
- Type: Clinical studies are inherently prospective.

3. Number of Experts Used to Establish the Ground Truth for the Test Set and Qualifications of Those Experts

This information is not provided in the given text. Clinical endpoints like patient survival and adverse events are typically recorded by clinical staff (doctors, nurses) as part of standard medical practice and trial protocols, rather than being "established" by a specific number of experts in a ground truth panel. The safety and efficacy data would be gathered by the clinical trial investigators.

4. Adjudication Method for the Test Set

This information is not provided in the given text. While clinical trials often have data monitoring committees or adjudication processes for serious adverse events, the specific method is not detailed here.

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

No, an MRMC comparative effectiveness study was not done. This type of study is relevant for diagnostic devices where human readers interpret medical images or data. Celsior is a medical solution used for organ preservation, not a diagnostic tool requiring reader interpretation.

6. Standalone (i.e., algorithm only without human-in-the-loop performance) Study

No, a standalone algorithm performance study was not done. Celsior is a medical solution, not an algorithm. The "performance" refers to its biological effect on organs and patient outcomes.

7. Type of Ground Truth Used

For the clinical studies, the "ground truth" was based on patient outcomes data, specifically:
- 7-day patient survival
- 30-day patient survival
- 30-day graft survival
- Cardiac-related serious adverse events
- Overall adverse event profiles
For preclinical studies, the "ground truth" was based on physiological performance metrics in isolated animal hearts and live animal models (e.g., "Celsior-treated hearts performed better than ViaSpan-treated hearts").
For biocompatibility, sterility, and stability studies, the "ground truth" was based on laboratory test results (e.g., cytotoxicity assays, sterility cultures, chemical stability analysis).

8. Sample Size for the Training Set

This concept of a "training set" is not applicable here as Celsior is not an AI/ML device. The clinical trials would involve a patient cohort, but it's not a "training set" in the machine learning sense. The text does not provide an overall sample size for the clinical trial, just that it was a "multicenter" trial conducted in the U.S.

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

As in point 8, this question is not applicable as there is no "training set" in the context of an AI/ML device. The clinical trial data for Celsior versus controls would be used for direct comparison to demonstrate substantial equivalence, not for training a model.

Summary

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SangStat Medical Corporation

Celsior™ 510(k)

K991694 p.1/4

510(k) Summary of Safety and Effectiveness Information 9.0

Date Prepared: July 30, 1999

I. Sponsor

A. Sponsor Name
SangStat Medical Corporation 6300 Dumbarton Circle Fremont, CA 94555 Telephone: (510) 789-4300 (510) 789-4205 Fax:

B. Official Correspondent

Mark D. Tolpin, M.D. Senior Vice President Worldwide Clinical Research & Regulatory Affairs SangStat Medical Corporation 6300 Dumbarton Circle Fremont, CA 94555 Telephone: (510) 789-4533 Fax: (510) 789-4205

II. System Identification

A. Proprietary Product Name
Celsior™ Cold Storage Solution
B. Common or Usual Product Name
Cold Storage Solution

C. Product Classification

Class II, Panel Number 78-KDL

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K991594 p.2/4

III. Predicate Device

A. Name

ViaSpan® (Belzer UW-CSS), Du Pont Pharmaceuticals (Wilmington, Delaware) [510(k) Notification Number K900492 and K883782], Class Code with Panel Number 78-KDL.

B. Indications for Use

The solution is intended for flushing and cold storage for organs including kidney, liver, and pancreas at the time of their removal from the donor in preparation for storage, transportation and eventual transplantation into a recipient.

C. Device Description

ViaSpan®, (Belzer UW-CSS) Cold Storage Solution (Du Pont Pharmaceuticals, Wilmington, Delaware), is a clear to light yellow, sterile, non-pyrogenic solution used for flushing and storage of human organs. This solution has an approximate calculated osmolarity of 320 mOsm, a sodium concentration of 29 mEq/L, a potassium concentration of 125 mEq/L, and a pH of roughly 7.4 at room The composition of ViaSpan is thus consistent with that of an temperature. intracellular solution.

Celsior™ Device Information IV.

A. Indications for Use

Celsior™ is intended to be used for flushing, storage, and transportation of hearts in preparation for eventual transplantation into a recipient.

B. Device Description

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K991594 p.3/4

Celsior™ 510(k)

V. Substantial Equivalence

A. Indications for Use

ViaSpan and Celsior have the same intended use. Both solutions are intended for the flushing and cold storage of an organ at the time of its removal from a donor in preparation for storage, transportation, and eventual transplantation into a recipient.

B. Technological Characteristics

Celsior and ViaSpan are clear to light yellow, sterile, non-pyrogenic solutions. Celsion's chemical composition has a number of similarities to that of ViaSpan. However, the potassium content of Celsior is more similar to that of an extracellular solution, whereas the potassium content of ViaSpan is more consistent with that of an intracellular solution. Both Celsior and ViaSpan contain impermeants, buffers, reduced glutathione, electrolytes, and water for injection. The impermeant in Celsior is mannitol and the buffer is histidine, while the impermeant in ViaSpan is pentafraction and the buffers are potassium hydroxide and sodium hydroxide.

C. Performance Data

To demonstrate that Celsior is substantially equivalent to ViaSpan for its intended uses, SangStat conducted three clinical studies and several nonclinical studies using Celsior. The study conducted in the U.S. (IDE file number G970052) was a multicenter, randomized, controlled, open-label clinical trial comparing Celsior to standard preservation solutions, including ViaSpan. The primary efficacy endpoint of seven (7) day patient survival was comparable between groups as were the secondary endpoints of 30 day patient and graft survival. In the first 30 days posttransplant, significantly fewer subjects receiving Celsior-treated hearts had one or more cardiac-related serious adverse events based on one-sided 95% confidence interval analysis. Clinical studies demonstrated that Celsior and ViaSpan had similar adverse event profiles and that adverse events using Celsior were also similar to that for other hospital solutions currently used to prepare hearts for transplant.

Preclinical studies conducted in isolated rabbit hearts and mongrel canines demonstrate that Celsior-treated hearts performed better than ViaSpan-treated hearts. Preclinical studies also demonstrate the biocompatibility (e.g., cyotoxicity, intracutaneous, in vitro hemolysis, in vivo hemolysis, osmotic fragility), sterility (ethylene oxide, ethylene chlorohydrin, and ethylene glycol), and stability of Celsior.

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K991594 p.4/4

VI. Conclusion

ViaSpan and Celsior have the same intended use. Data contained in the 510(k) demonstrate that Celsior is substantially equivalent.

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Food and Drug Administration 9200 Corporate Boulevard Rockville MD 20850

AUG - 5 1999

Mark D. Tolpin, M.D Senior Vice President Worldwide Clinical Research and Requiatory Affairs SangStat Medical Corporation 1505 Adams Drive Menlo Park, CA 94025

Re: K991594. Celsior™ Cold Flush, Storage and Transport Solution for Hearts Dated: May 6, 1999 Received: Mav 7. 1999 Regulatory Class: II 21 CFR §876.5880/Procode: 78 MSB

Dear Dr. Tolpin:

We have reviewed your Section 510(k) notification of intent to market the device referenced above and we 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). 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.

If your device is classified (see above) into either class II (Special Controls) or class III (Premarket Approval), it may be subject to such additional controls. Existing major regulations affecting your device can be found in the Code of Federal Regulations, Title 21, Parts 800 to 895. A substantially equivalent determination assumes compliance with the Current Good Manufacturing Practice requirements, as set forth in the Quality System Regulation (QS) for Medical Devices: General regulation (21 CFR Part 820) and that, through periodic QS inspections, the Food and Drug Administration (FDA) will verify such assumptions. Failure to comply with the GMP regulation may result in regulatory action. In addition, FDA may publish further announcements concerning your device in the Federal Register. Please note: this response to your premarket notification submission does not affect any obligation you might have under sections 531 through 542 of the Act for devices under the Electronic Product Radiation Control provisions, or other Federal laws or regulations,

This letter will allow you to begin marketing your device as described in your 510(t) premarket notification. The FDA finding of substantial equivalence of your device to a legally marketed predicate device results in a classification 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 and additionally 809.10 for in vitro diagnostic devices), piease contact the Office of Compliance at (301) 594-4613. Additionally, for questions on the promotion and advertising of your device, please contact the Office of Compliance at (301) 594-4639. Also, please note the regulation entitled, "Misbranding by reference to premarket notification"(21 CFR 807.97). Other general information on your responsibilities under the Act may be obtained from the Division of Small Manufacturers Assistance at its toll-free number (800) 638-2041 or (301) 443-6597, or at its internet address "http://www.fda.gov/cdrh/dsma/dsmamain.html".

Sincerely yours,

CAPT Daniel G. Schultz, M.D. Acting Director, Division of Reproductive, Abdominal, Ear, Nose and Throat, and Radiological Devices Office of Device Evaluation Center for Devices and Radiological Health

Enclosure

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510(k) Number (if known):	Subject of this Submission
Device Name:	Celsior™ Cold Flush, Storage and Transport Solutionfor Hearts
Indications for Use:	Celsior™ is intended for flushing and cold storage of aheart at the time of its removal from a donor inpreparation for storage, transportation, and eventualtransplantation into a recipient.

(Please Do Not Write Below This Line - Continue On Another Page If Needed Concurrence of CDRH, Office of Device Evaluation (ODE)

Prescription Use # (Per 21 CFR §801.109)

Over-The-Counter Use (Optional Format 1-2-96)

David C. Digman

(Division Sign-Off) Division of Reproductive, Abdominal, ENT, Division of Reproductive, and Radiological Devices
and Radiological Devices
5100k) Number 991596 510(k) Number _

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).