PEREGRINE RADIATION THERAPY DOSE CALCULATION SYSTEM by NOMOS CORP.

The PEREGRINE™ Radiation Therapy Dose Calculation System is intended to be used for radiation therapy in conjunction with a Radiation Treatment Planning system to calculate dose distributions. It is to be used by the physician and/or other competent health aooo alombation clinical review and judgement of radiation treatment plans. The goal of the protections is to produce consistent highly accurate dose calculations using the Monte Carlo algorithms.

The PEREGRINE™ Radiation Therapy Dose Calculation System is used in conjunction with a radiation treatment planning system to provide the dose distribution for radiation therapy treatments employing radiation sources and associated beam modifiers for clinical review and judgement prior to treating the patient. The PEREGRINE™ Radiation Therapy Dose Calculation System is intended to be used by a competent health professional such as a radiation oncologist, medical physicist, radiation therapist, or dosimetrist.

Device Description

The PEREGRINE Radiation Therapy Dose Calculation System is a 3-D Monte Carlo radiation transport system designed to provide accurate dose calculations for radiation therapy treatment planning. PEREGRINE combines Monte Carlo-based modeling of the accelerator beam production system, Monte Carlo simulation of treatment-specific beam modifiers and Monte Carlo transport in the patient to provide a robust and accurate representation of the radiation source, beam modifiers and heterogeneities in the patient. PEREGRINE has been designed to provide highly accurate, high resolution radiation dose calculations rapidly on economical, commercially available computer microprocessors and to be easily integrated with commercial radiation treatment planning systems. In order to ensure its accuracy, PEREGRINE has been verified against a comprehensive set of clinical measurements designed to stress the physics algorithms for a full range of clinically relevant materials, densities and beam energies for open, blocked, wedged and compensated fields incident on both simple phantoms and phantoms with a variety of surface and sub-surface heterogeneities.

AI/ML Overview

Here's an analysis of the acceptance criteria and study information for the PEREGRINE™ Radiation Therapy Dose Calculation System, based on the provided text:

1. Table of Acceptance Criteria and Reported Device Performance

The provided text does not contain explicit, quantitative acceptance criteria or a direct table comparing them to reported device performance. It generally states that the device "meets the design criteria and user needs" and that "Test completion shows that the device performs and is substantially equivalent to the predicate system."

However, we can infer the intent of the acceptance criteria from the device description and the non-clinical tests. The overarching criterion is accuracy of dose calculations.

Acceptance Criteria (Inferred)	Reported Device Performance
Accuracy of 3-D Monte Carlo radiation transport calculations across a full range of clinically relevant materials, densities, and beam energies.	PEREGRINE verified against a comprehensive set of clinical measurements designed to stress the physics algorithms for a full range of clinically relevant materials, densities and beam energies for open, blocked, wedged and compensated fields incident on both simple phantoms and phantoms with a variety of surface and sub-surface heterogeneities.
Robustness and accurate representation of the radiation source, beam modifiers, and heterogeneities in the patient.	PEREGRINE combines Monte Carlo-based modeling of the accelerator beam production system, Monte Carlo simulation of treatment-specific beam modifiers and Monte Carlo transport in the patient to provide a robust and accurate representation of the radiation source, beam modifiers and heterogeneities in the patient.
High accuracy, high resolution radiation dose calculations.	PEREGRINE has been designed to provide highly accurate, high resolution radiation dose calculations.
Safety and effectiveness of the software.	Validation and verification testing of the PEREGRINE Radiation Therapy Dose Calculation System demonstrate that the software is safe and effective.
Substantial equivalence to the predicate device (ADAC Laboratories Pinnacle3 3D Treatment Planning Throughput K926008).	Test completion shows that the device performs and is substantially equivalent to the predicate system for those features for which this submission is being made as well as overall performance.
Compliance with design criteria and user needs.	Verification and validation tests were completed in accordance with the test plans. They prove that the PEREGRINE Radiation Therapy Dose Calculation System meets the design criteria and user needs.

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

Sample Size: The text states that the device was "verified against a comprehensive set of clinical measurements." It does not specify a numerical sample size for this test set (e.g., number of patients, number of phantom configurations).
Data Provenance: The measurements are referred to as "clinical measurements," implying they reflect a real-world clinical context, but it doesn't specify the country of origin. The study appears to be prospective in the sense that the measurements were likely taken specifically for the verification of the PEREGRINE system, rather than retrospectively collected from existing patient data.

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

The text does not provide information on the number of experts used or their qualifications for establishing ground truth for the test set. The ground truth appears to be based on "clinical measurements" and the physics principles inherent in Monte Carlo simulations.

4. Adjudication Method for the Test Set

The text does not specify any adjudication method (e.g., 2+1, 3+1, none) for the test set. The verification seems to rely on the direct comparison of the system's calculations against the "comprehensive set of clinical measurements."

5. If a Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study Was Done, and Effect Size

No, a Multi-Reader Multi-Case (MRMC) comparative effectiveness study was not mentioned or described in the provided text. The evaluation focuses on the standalone performance of the dose calculation system, not on its impact on human reader performance.

6. If a Standalone (i.e., algorithm only without human-in-the-loop performance) Was Done

Yes, a standalone (algorithm only) performance evaluation was done. The description of the verification process—"verified against a comprehensive set of clinical measurements designed to stress the physics algorithms"—directly pertains to the algorithm's performance in generating dose calculations. The system is designed to "provide accurate dose calculations" and its "accuracy" was verified. There is no mention of physician interaction being part of this core verification.

7. The Type of Ground Truth Used

The primary type of ground truth used was clinical measurements. These measurements were used to stress the physics algorithms, implying they represent real-world physical dose distributions, likely obtained from dosimetric equipment in phantoms.

8. The Sample Size for the Training Set

The text does not specify a sample size for the training set. It refers to the system's development using "design controls" and "Quality system design control and product release procedures," indicating a structured development process, but no details on training data are provided. As a dose calculation system based on physical models (Monte Carlo), it may not have a "training set" in the same way a machine learning algorithm would, but rather internal physics parameters and models derived from fundamental principles and potentially calibrated against general physical data.

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

The text does not explicitly describe how ground truth for any "training set" was established. Given the nature of a Monte Carlo radiation transport system, its core "ground truth" for development would likely be based on fundamental physics laws, established physical constants, and potentially extensive experimental data from various radiation sources and materials, rather than a specific "training set" with established ground truth by human experts in the context of typical AI/ML development. The "modeling of the accelerator beam production system" and "simulation of treatment-specific beam modifiers" would rely on established physics and engineering data.

Summary

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K993675
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Tab 2 510(k) Summary of Safety and Effectiveness PEREGRINE™ Radiation Therapy Dose Calculation System

Pursuant to Section 513(l) of the Federal food, Drug, and Cosmetic Act and 21 CFR 807.92:

NOMOS Corporation

(a) (1) Submitter's address:	2591 Wexford Bayne RoadSewickley, PA 15143
(a) (1) Submitter's telephone number:	(724) 934-8200
(a) (1) Contact person:	William O. ChishkoDirector, Quality and Regulatory Affairs
(a) (1) Date summary was prepared:	October 26, 1999
(a) (2) Trade or proprietary name:	PEREGRINE™ Radiation Therapy Dose CalculationSystem
(a) (2) Common or usual name:	Radiation Therapy Dose Calculation System
(a) (2) Classification name:	Accelerator, Linear, Medical, Accessory

ADAC Laboratories Pinnacle3 3D Treatment K926008 Planning Throughput

(a) (4) Device description:

(a) (3) Predicate device:

(a) (1) Submitter's name:

90 IYE [21 CFR 892.5050]

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K993675
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(a) (5) Intended use:

The PEREGRINE Radiation Therapy Dose Calculation System is intended to be used for radiation therapy in conjunction with a Radiation Treatment Planning system to calculate dose distributions. It is to be used by the physician and/or other competent health aooo alombation clinical review and judgement of radiation treatment plans. The goal of the protections is to produce consistent highly accurate dose calculations using the Monte Carlo algorithms.

(a) (6) Technological characteristics:

The PEREGRINE Radiation Therapy Dose Calculation System is designed to interface to radiation treatment planning systems using industry standard protocols. It was developed and tested using Quality system design control and product release procedures.

(b) (1) Non-clinical tests submitted:

The PEREGRINE Radiation Therapy Dose Calculation System was developed and tested using the design controls set forth in the NOMOS Corporation Quality System. Some aortions of the system were developed and tested at Lawrence Livermore National Laboratories using design controls set forth in Lawrence Livermore National Laboratories Quality System. This system was audited by NOMOS and found to be compliant with the requirements of the NOMOS Quality System as well as the regulatory requirements of the FDA Quality System Regulations and EC Medical Device Directive. It has a product specification, which was used as the basis for the development of verification and validation plans, tests and acceptance criteria. A rigorous hazard analysis also was performed, which includes mitigation for each identified hazard. Verification and validation tests were completed in accordance with the test plans. They prove that the PEREGRINE Radiation Therapy Dose Calculation System meets the design criteria and user needs. Design reviews were conducted at appropriate stages of development.

(b) (3) Test Conclusions:

Validation and verification testing of the PEREGRINE Radiation Therapy Dose Calculation System demonstrate that the software is safe and effective. Test completion shows that the device performs and is substantially equivalent to the predicate system for those features for which this submission is being made as well as overall performance. Product release also is made in accordance with established NOMOS Corporation Quality System Procedures after all tests are completed, reviewed and meet acceptance criteria and regulatory requirements.

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DEPARTMENT OF HEALTH & HUMAN SERVICES

Food and Drug Administration 9200 Corporate Boulevard Rockville MD 20850

P = 5 2000

Francis X. Dobscha Director of Quality and Regulatory Affairs NOMOS Corporation 2591 Wexford Bayne Road Sewickley, PA 15143

Re: K993675

Peregrine™ Radiation Therapy Dose Calculation System Dated: July 11, 2000 Received: July 13, 2000 Regulatory Class: II 21 CFR 892.5050/Procode: 90 MUJ

Dear Mr. Dobscha:

We have reviewed your Section 510(k) notification of intent to market the device referenced above and we have decemined 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). 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 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(k) 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), please contact the Office of Compliance at (301) 594-4639. 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" (21CFR 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/cdrfvdsma/dsmamain.html".

Sincerely yours,

Daniel C. Schultz, M.D.

Daniel G. Schultz, M.D. Captain, USPHS Acting Director, Division of Reproductive, Abdominal, and Radiological Devices Office of Device Evaluation Center for Devices and Radiological Health

Enclosure (s)

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Page 1 of 1 993675 510(k) Number [if known]: Device Name: PEREGRINE™ Radiation Therapy Dose Calculation System Indication for Use:

ISE DO NOT WRITE BELOW THIS LINE. CONTINUE ON ANOTHER PAGE AS NEEDED]

Concurrence of the CDRH Office of Device Evaluation [ODE]

Prescription Use (Per 21 CFR 801.109)

Over the Counter Use (Optional Format , 2 January

1996

David A. Severson

(Division Sign-Off) Division of Reproductive, Abdominal, ENT, and Radiological Devices 510(k) Number_1

Regulation Number and Section

§ 892.5050 Medical charged-particle radiation therapy system.

(a)
Identification. A medical charged-particle radiation therapy system is a device that produces by acceleration high energy charged particles (e.g., electrons and protons) intended for use in radiation therapy. This generic type of device may include signal analysis and display equipment, patient and equipment supports, treatment planning computer programs, component parts, and accessories.(b)
Classification. Class II. When intended for use as a quality control system, the film dosimetry system (film scanning system) included as an accessory to the device described in paragraph (a) of this section, is exempt from the premarket notification procedures in subpart E of part 807 of this chapter subject to the limitations in § 892.9.