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CUSTODIOL® HTK solution is indicated for perfusion and flushing of donor kidneys, liver, pancreas and heart prior to removal from the donor or immediately after removal from the donor. The solution is left in the organ vasculature during hypothermic storage and transportation to the patient. CUSTODIOL® HTK solution is not indicated for continuous machine perfusion of donor organs.

The CUSTODIOL® HTK solution is intended for perfusion and flushing donor kidney, liver, heart, and pancreas prior to removal from the donor and for preserving these organs during hypothermic storage and transport to the recipient. CUSTODIOL® HTK solution is based on the principle of inactivating organ function by withdrawal of extracellular sodium and calcium, together with intensive buffering of the extracellular space by means of histidine/histidine HCI, so as to prolong the period for which the organs will tolerate interruption of blood and oxygen supply. Only a small portion of the osmolality of the CUSTODIOL® HTK solution is due to the sodium and potassium. The composition of HTK is similar to that of extracellular fluid. All of the components of the CUSTODIOL® HTK solution occur naturally in the body. The CUSTODIOL® HTK solution is relatively low in potassium concentration so that residual solution in the transplanted organ poses no danger to the recipient. This is particularly important in orqans that take up relatively large amounts of the perfusate, which may find its way into the recipient's circulation. The CUSTODIOL® HTK solution has a low viscosity, even at low temperatures. This characteristic assures rapid flow rates during initial perfusion, allowing the organ to be quickly cooled.

This document is a 510(k) premarket notification for the CUSTODIOL® HTK Solution, an organ preservation solution. It focuses on demonstrating substantial equivalence to a previously cleared predicate device (K043461), rather than outlining specific performance criteria and a study to prove they are met in a traditional sense for a new AI/diagnostic device.

Therefore, many of the requested categories (e.g., sample size for test set, number of experts for ground truth, adjudication method, MRMC study, standalone performance) are not applicable or cannot be extracted from this type of regulatory submission. The document primarily focuses on comparing the new device to a predicate based on existing data and prior clearances.

Here's a breakdown of what can be extracted and what cannot:

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

The document does not present "acceptance criteria" and "reported device performance" in the typical format of a diagnostic or AI device where specific metrics (e.g., sensitivity, specificity, AUC) are measured against predefined thresholds. Instead, the "acceptance criterion" for this 510(k) is demonstrating substantial equivalence to the predicate device.

The "reported device performance" is essentially the demonstrated similarity across various characteristics, supported by existing data and non-clinical testing.

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

This information is not provided in this 510(k) submission. The document relies on existing data, standards, and non-clinical testing to demonstrate substantial equivalence, rather than a specific new clinical "test set" with a defined sample size for performance evaluation. The "non-clinical testing" mentioned for packaging differences likely involved laboratory tests, not a patient-based test set.

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 information is not applicable/not provided. This is a device for organ preservation, not an AI/diagnostic device that generates an output requiring expert interpretation or "ground truth" establishment in the context of a diagnostic study.

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

This information is not applicable/not provided. See point 3.

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

This information is not applicable/not provided. This is not an AI-assisted diagnostic device.

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

This information is not applicable/not provided. This is an organ preservation solution, not an algorithm.

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

This information is not applicable/not provided in the context of a new study to establish "ground truth" for a performance evaluation. The "ground truth" here is the established safety and efficacy of the predicate device, and the substantial equivalence of the current device to that predicate based on physico-chemical properties, biological characteristics, and non-clinical testing.

8. The sample size for the training set

This information is not applicable/not provided. There is no "training set" as this is not an AI/machine learning device.

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

This information is not applicable/not provided. There is no "training set" for this type of device submission.

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Custodiol HTK Solution is indicated for perfusion and flushing donor kidneys, liver, pancreas, and heart prior to removal from the donor or immediately after removal from the donor. The solution is left in the organ vasculature during hypothermic storage and transportation (not for continuous perfusion) to the recipient.

The HTK solution is intended for perfusion and flushing donor kidney, liver, heart, and pancreas prior to removal from the donor and for preserving these organs during hypothermic storage and transport to the recipient. HTK solution is based on the principle of inactivating organ function by withdrawal of extracellular sodium and calcium, together with intensive buffering of the extracellular space by means of histidine/histidine HCI, so as to prolong the period for which the organs will tolerate interruption of blood and oxygen supply. Only a small portion of the osmolality of the HTK solution is due to the sodium and potassium. The composition of HTK is similar to that of extracellular fluid. All of the components of the HTK solution occur naturally in the body. The HTK solution is relatively low in potassium concentration so that residual solution in the transplanted organ poses no danger to the recipient. This is particularly important in organs that take up relatively large amounts of the perfusate, which may find its way into the recipient's circulation. The HTK solution has a low viscosity, even at low temperatures. This allows the organ to be quickly cooled.

Here's a breakdown of the acceptance criteria and study information for the Custodiol® HTK Solution, based on the provided text:

1. Table of Acceptance Criteria and Reported Device Performance

The provided document is a 510(k) summary, which focuses on demonstrating substantial equivalence to a predicate device rather than defining specific performance acceptance criteria like often seen for novel AI/medical imaging devices. For drug or solution products like Custodiol HTK Solution, "performance" is typically measured by clinical outcomes related to organ preservation effectiveness.

Therefore, the "acceptance criteria" here are implicitly tied to the performance of the legally marketed predicate devices, and the "reported device performance" is the demonstration that Custodiol HTK Solution performs similarly.

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

• Test Set Sample Size: The document states that "a small number of independent clinical studies" were used to demonstrate equivalence. It does not specify the exact sample sizes for these studies.
• Data Provenance: The studies are described as "independent clinical studies," suggesting real-world data, likely prospective or retrospective clinical trials comparing outcomes. The country of origin is not specified.

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

This type of information (number and qualifications of experts) is typically relevant for studies involving subjective assessment (e.g., image interpretation). For a solution like Custodiol HTK, the "ground truth" for its effectiveness is generally established by objective clinical outcomes (e.g., organ survival rates, transplant success) rather than expert consensus on a subjective measure. Therefore, this question is not applicable in the traditional sense for this device.

4. Adjudication Method for the Test Set

As the "ground truth" is based on objective clinical outcomes, an adjudication method for subjective assessments is not applicable. Clinical studies generally have established protocols for data collection and outcome assessment, but not a "2+1" or "3+1" adjudication model for interpreting performance.

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

• No, an MRMC comparative effectiveness study was not done. This type of study is specifically designed for evaluating diagnostic devices or AI algorithms that assist human readers in interpreting images or data.
• The Custodiol HTK Solution is an organ preservation solution, not an AI-powered diagnostic tool. Therefore, this question is not applicable.

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

• No, a standalone (algorithm-only) performance study was not done.
• The Custodiol HTK Solution is a medical product (chemical solution), not an algorithm or AI. Therefore, this question is not applicable.

7. The Type of Ground Truth Used

The ground truth used was primarily clinical outcomes data, specifically:

• "Survival rates"
• "Other outcome measures" (likely related to organ function post-transplant, rejection rates, etc.)

8. The Sample Size for the Training Set

• Not applicable. As this is a medical solution and not a machine learning algorithm, there is no "training set" in the context of AI development. The "training" or development of the solution would involve pharmaceutical research and chemical formulation, not data-driven model training.

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

• Not applicable. There is no "training set" or corresponding "ground truth" as defined for AI/ML devices. The "ground truth" for the overall effectiveness of the solution is established through clinical studies (as mentioned in point 7).

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Custodiol HTK Solution is indicated for perfusion and flushing donor kidneys, livers, and hearts prior to removal from the donor or immediately after removal from the donor. The solution is left in the organ vasculature during hypothermic storage and transportation (not for continuous perfusion) to the recipient.

The HTK solution is intended for perfusion and flushing donor hearts prior to removal from the donor and for preserving the heart during hypothermic storage and transport to the recipient. HTK solution is based on the principle of inactivating organ function by withdrawal of extracellular sodium and calcium, together with intensive buffering of the extracellular space by means of histidine/histidine HCI, so as to prolong the period for which the organs will tolerate interruption of blood and oxygen supply. Only a small portion of the osmolality of the HTK solution is due to the sodium and potassium. The composition of HTK is similar to that of extracellular fluid. All of the components of the HTK solution occur naturally in the body. The HTK solution is relatively low in potassium concentration so that residual solution in the transplanted organ poses no danger to the recipient. This is particularly important in organs that take up relatively large amounts of the perfusate, which may find its way into the recipient's circulation. The HTK solution has a low viscosity, even at low temperatures. This characteristic assures rapid flow rates during initial perfusion, allowing the organ to be quickly cooled.

The provided text is a 510(k) summary for the Custodiol HTK Solution, which is a medical device for organ preservation. It does not contain information about acceptance criteria or a study proving that a device meets acceptance criteria in the generalized sense of a diagnostic, imaging, or AI-powered device. Instead, it describes clinical studies comparing the performance of the Custodiol HTK Solution with predicate devices to demonstrate its substantial equivalence for organ preservation.

Therefore, many of the requested categories (e.g., sample size for test set, number of experts, adjudication method, MRMC study, standalone performance, training set details) are not applicable to this type of submission.

Here's a breakdown of the available information:

1. Table of Acceptance Criteria and Reported Device Performance:

The 510(k) summary does not define explicit "acceptance criteria" in a quantitative sense as might be seen for a diagnostic or imaging device (e.g., sensitivity, specificity thresholds). Instead, the "acceptance criteria" are implicitly met by demonstrating substantial equivalence to legally marketed predicate devices in terms of performance and safety for organ preservation. The reported device performance is related to survival rates and other outcome measures of transplanted organs.

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

• Test Set Sample Size: "a small randomized clinical study" and "extensive experience of the largest heart transplant center in the world." Specific numbers are not provided.
• Data Provenance: Not explicitly stated (e.g., country of origin), but reference to "the largest heart transplant center in the world" suggests a clinical setting. The studies are clinical in nature. The term "retrospective or prospective" is not used, but "clinical studies have been reported" implies real-world data collection.

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

Not applicable. The "ground truth" here would relate to organ viability and patient outcomes, which are objective clinical measures rather than expert interpretations of data (like radiology reads).

4. Adjudication method for the test set:

Not applicable for this type of device and study.

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 not an AI or diagnostic imaging device that involves human readers.

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

Not applicable. This is a chemical solution, not an algorithm.

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

The "ground truth" largely refers to clinical outcomes data, specifically "survival rates and other outcome measures" of transplanted organs.

8. The sample size for the training set:

Not applicable. This is not a machine learning device with a training set. The clinical studies mentioned serve as the basis for demonstrating equivalence.

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

Not applicable.

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Custodiol HTK Solution is indicated for perfusion and flushing donor kidneys and liver prior to removal from the donor or immediately after removal from the donor. The solution is left in the organ vasculature during hypothermic storage and transportation (not for continuous perfusion) to the recipient.

The HTK solution is intended for perfusion and flushing donor kidneys and liver prior to removal from the donor and for preserving the kidney during hypothermic storage and transport to the recipient. HTK solution is based on the principle of inactivating organ function by withdrawal of extracellular sodium and calcium, together with intensive buffering of the extracellular space by means of histidine/histidine HCI, so as to prolong the period for which the organs will tolerate interruption of blood and oxygen supply. Only a small portion of the osmolality of the HTK solution is due to the sodium and potassium. The composition of HTK is similar to that of extracellular fluid. All of the components of the HTK solution occur naturally in the body. The HTK solution is relatively low in potassium concentration so that residual solution in the transplanted organ poses no danger to the recipient. This is particularly important in organs that take up relatively large amounts of the perfusate, which may find its way into the recipient's circulation. The HTK solution has a low viscosity, even at low temperatures. This characteristic assures rapid flow rates during initial perfusion, allowing the organ to be quickly cooled.

The provided text describes the performance of Custodiol® HTK Solution in comparison to a predicate device (Viaspan Belzer UW Cold Storage Solution) for liver preservation. However, it does not outline explicit "acceptance criteria" in the format of defined thresholds that the device must meet. Instead, the study aims to demonstrate "substantial equivalence" based on clinical outcomes, particularly patient and graft survival rates.

Here's an analysis based on the information provided, framed around the concepts requested:

1. Table of Acceptance Criteria and Reported Device Performance:

As explicit acceptance criteria were not stated as numerical thresholds (e.g., "must achieve X% survival"), the table below reflects the comparative performance of the Custodiol HTK Solution against the predicate (UW solution) and general outcomes when using HTK, which served as the basis for demonstrating equivalence. The "Acceptance Criteria" here are inferred to be "survival rates at least as good as, and not significantly different from, the predicate device (Viaspan Belzer UW Cold Storage Solution) or generally accepted outcomes for liver transplantation using similar preservation methods."

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

• Four-Center Prospective Clinical Study (Eurotransplant):
  • Sample Size: 228 livers
  • Data Provenance: Prospective, from four centers located at Essen, Innsbruck, Göttingen, and Vienna (Europe, specifically Germany and Austria).
• Randomized Prospective Study (Essen):
  • Sample Size: 60 livers (30 preserved with HTK, 30 preserved with UW solution).
  • Data Provenance: Prospective, from Essen (Germany).
• Retrospective Study (Hanover):
  • Sample Size: 747 liver transplants (515 using UW solution, 232 using HTK solution). These involved 416 patients (UW) and 197 patients (HTK), with some re-transplants.
  • Data Provenance: Retrospective, from Medizinische Hochschule Hanover, Clinic for Abdominal and Transplantation Surgery (Germany).

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

The document describes clinical studies measuring patient and graft survival rates, which are direct clinical outcomes. It does not mention the use of experts to establish a "ground truth" for the test set in the sense of independent adjudication or labeling of images/data, as would be typical for diagnostic AI devices. The outcomes (survival rates) are objectively measured clinical events.

4. Adjudication Method for the Test Set:

Not applicable in the context of this device. The studies directly measured clinical outcomes (patient and graft survival), which are not typically subject to an adjudication process in the way a diagnostic interpretation would be.

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 medical solution (organ preservation fluid), not a diagnostic 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 medical solution, not an algorithm.

7. The Type of Ground Truth Used:

The "ground truth" used in these studies was outcomes data, specifically:

• Patient survival (mortality)
• Graft survival (failure of the transplanted organ)

These are direct, objective clinical endpoints.

8. The Sample Size for the Training Set:

Not applicable. This is a medical solution, not a machine learning algorithm requiring a training set. The clinical studies described are for validation/comparison, not for training a model.

9. How the Ground Truth for the Training Set was Established:

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

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Custodiol HTK Solution is indicated for perfusion and flushing donor kidneys prior to removal from the donor or immediately after removal from the donor. The solution is left in the organ vasculature during hypothermic storage and transportation (not for continuous perfusion) to the recipient.

The HTK solution is intended for perfusion and flushing donor kidneys prior to removal from the donor and for preserving the kidney during hypothermic storage and transport to the recipient. HTK solution is based on the principle of inactivating organ function by withdrawal of extracellular sodium and calcium, together with intensive buffering of the extracellular space by means of histidine/histidine HCl, so as to prolong the period for which the organs will tolerate interruption of blood and oxygen supply. Only a small portion of the osmolality of the HTK solution is due to the sodium and potassium. The composition of HTK is similar to that of extracellular fluid. All of the components of the HTK solution occur naturally in the body.

The HTK solution is relatively low in potassium concentration so that residual solution in the transplanted organ poses no danger to the recipient. This is particularly important in organs that take up relatively large amounts of the perfusate, which may find its way into the recipient's circulation.

The HTK solution has a low viscosity, even at low temperatures. This characteristic assures rapid flow rates during initial perfusion, allowing the organ to be quickly cooled.

Here's an analysis of the provided 510(k) summary regarding the Custodiol® HTK Solution, focusing on acceptance criteria and the study that proves its equivalence:

1. Table of Acceptance Criteria and Reported Device Performance

Note: The acceptance criteria are implicitly derived from the performance of the predicate device (Viaspan Belzer UW Cold Storage Solution), as the study aims to demonstrate "as well as" performance.

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

• Sample Size: "Over a thousand kidneys" were included in the study.
• Data Provenance: The study was a "47-center randomized clinical study carried out under the guidance of the Eurotransplant organization of Leiden, The Netherlands." This indicates prospective data from multiple European centers.

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

This information is not provided in the document. The study focuses on "overall kidney survival rates" as outcome measures, which are clinical outcomes rather than expert-established ground truth in an imaging or diagnostic sense. The determination of kidney survival likely relies on standardized clinical criteria and medical records, rather than expert interpretation of a specific artifact.

4. Adjudication Method for the Test Set

This information is not explicitly provided. Given the nature of kidney survival rates as the primary outcome, it's unlikely that the "adjudication method" in the context of expert review (e.g., 2+1, 3+1) is directly applicable. Outcomes like kidney survival are typically determined by clinical follow-up and documented medical facts.

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 comparison of two organ preservation solutions, not an AI-assisted diagnostic device. Therefore, a MRMC study with human readers and AI assistance is not relevant to this submission.

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

Not Applicable. This is a medical solution, not an algorithm or AI device.

7. The Type of Ground Truth Used

The ground truth used was outcomes data, specifically "overall kidney survival rates." These rates are clinical outcomes reflecting the functional status of the transplanted kidneys over time.

8. The Sample Size for the Training Set

Not Applicable. This is not a machine learning or AI device that requires a distinct training set. The clinical study described served as the primary performance evaluation.

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

Not Applicable. As there is no training set in the context of an AI/ML device, this question is not relevant. The "ground truth" for the performance evaluation (kidney survival) was established through clinical follow-up and medical documentation within the multi-center study.

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