The INTRABEAM® System is indicated for radiation therapy treatments. The INTRABEAM® Spherical Applicators are indicated for use with the INTRABEAM® System to deliver a prescribed dose of radiation to the treatment margin or turnor bed during intracavity and intraoperative radiotherapy treatments.

The INTRABEAM® Spherical Applicators used with the INTRABEAM System are able to deliver a prescribed dose of intraoperative radiation in conjunction with whole breast irradiation, based upon the medical judgment of the physician. The safety and effectiveness of the INTRABEAM System as a replacement for whole breast irradiation in the treatment of breast cancer has not been established.

Device Description

The INTRABEAM System is a miniature, high-dose rate, low energy X-ray source that emits Xray radiation intraoperatively for the treatment of cancer at the tumor cavity. The INTRABEAM Spherical applicators are accessories to the INTRABEAM System. The INTRABEAM Spherical Applicators received 510(k) clearance in K992577. There are eight sizes of applicators in a set ranging from 1.5 cm to 5.0 cm in diameter. The INTRABEAM Spherical Applicators have not changed in design or technological characteristics as described in K992577.

AI/ML Overview

Here's an analysis of the provided text regarding the INTRABEAM® System with INTRABEAM® Spherical Applicators, focusing on acceptance criteria and the supporting study:

1. Table of Acceptance Criteria and Reported Device Performance

The provided text does not explicitly state quantitative "acceptance criteria" in the typical sense (e.g., target accuracy, sensitivity, specificity thresholds) for a diagnostic AI device. Instead, the "acceptance criteria" appear to be based on a non-inferiority finding from a clinical trial, comparing the device's outcome to standard treatment.

Therefore, the table below reflects the primary clinical outcome used to support the device's expanded indication, interpreted as the "performance" that met the "acceptance" for the new indication.

Acceptance Criterion (Implicit)	Reported Device Performance (INTRABEAM + Whole Breast Irradiation)	Comparator Performance (Whole Breast Irradiation Alone)
Non-inferior local control rate of breast cancer when IORT is used in conjunction with whole breast irradiation.	1.2% recurrence rate	0.95% recurrence rate
Statistical Significance	p=0.41 (non-significant difference)	N/A

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

Sample Size (TARGIT-A Trial): N=2,232
Data Provenance: "international, prospective, randomized" study. This indicates data was collected from various countries and in a forward-looking manner, specifically for the trial.

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

The document does not specify the number of experts or their qualifications for establishing the "ground truth" (e.g., recurrence diagnosis) within the TARGIT-A trial. However, as a large, international Phase 3 non-inferiority clinical trial on cancer treatment, it can be reasonably inferred that:

Diagnosis of recurrence would have been established by a multidisciplinary team of qualified medical professionals, including oncologists, pathologists, and radiologists, adhering to strict clinical trial protocols.
The investigators themselves were "physicians around the world".

4. Adjudication Method for the Test Set

The document does not explicitly state an adjudication method (like 2+1, 3+1). As a large-scale clinical trial studying recurrence rates, the "ground truth" for local control (recurrence) would typically be determined by clinical follow-up and confirmed diagnostic procedures as part of the trial's defined endpoints, rather than a separate expert review panel for each case. Any ambiguous cases would likely follow the trial's pre-defined adjudication process, often involving an independent endpoint committee, though this is not detailed.

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

No, a Multi-Reader Multi-Case (MRMC) comparative effectiveness study was not done in the context of this 510(k). The study described (TARGIT-A trial) is a clinical trial comparing treatment modalities (IORT vs. whole breast irradiation), not a study evaluating human readers' diagnostic performance with or without AI assistance. The INTRABEAM System is a device for delivering radiation therapy, not a diagnostic AI tool for image interpretation.

6. Standalone (Algorithm Only Without Human-in-the-Loop) Performance Study

Yes, in a sense, the TARGIT-A trial can be considered a standalone performance study of the treatment modality. The trial compared the clinical outcome (local recurrence rate) of patients receiving INTRABEAM IORT (in conjunction with whole breast irradiation) versus those receiving whole breast irradiation alone. The device's "performance" in this context is its ability to achieve comparable clinical outcomes regarding breast cancer recurrence. The "algorithm" here is the treatment protocol involving the INTRABEAM system.

7. Type of Ground Truth Used

The ground truth used in the TARGIT-A trial was clinical outcomes data, specifically:

Local control of breast cancer (i.e., presence or absence of recurrence).

This would be determined through patient follow-up, physical examinations, imaging studies, and potentially biopsy/pathology to confirm recurrence.

8. Sample Size for the Training Set

This information is not applicable as the INTRABEAM System is a medical device for radiation therapy delivery, not an AI algorithm that requires a training set in the typical machine learning sense. The "training" for practitioners would involve learning how to operate the device and apply the treatment based on clinical guidelines and the evidence from trials like TARGIT-A.

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

This information is not applicable for the same reasons as point 8. The device's efficacy is established through clinical trials, not through training on labeled datasets.

Summary

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Carl Zeiss Meditec Premarket Notification 510(k)

SECTION 2: 510(K) SUMMARY 1

DEC 2 7 2012

510(k) SUMMARY (per 21 CFR §807.92)

INTRABEAM® System with INTRABEAM® Spherical Applicators

General Information

Manufacturer:

Carl Zeiss Meditec AG Carl-Zeiss-Strasse 22 D-73447 Oberkochen Germany Est. Reg. No. 9615010

Contact Person:

Sarah Harrington, MS, MBA Staff Regulatory Specialist Carl Zeiss Meditec Inc. 5160 Hacienda Drive Dublin, California 94568 Phone: (925) 560-5134 FAX: (925) 557-4259 Email: s.harrington@meditec.zeiss.com

Device Name/Classification

Trade/Proprietary name:	INTRABEAM® System with INTRABEAM® SphericalApplicators
Common/Usual Name:	X-ray radiation therapy system
Classification name:	System, Therapeutic, X-ray
Classification:	Class II (21 CFR 892.5900)
Product Code:	JAD

Predicate Devices

Company: Device:

Carl Zeiss Meditec AG INTRABEAM® System with INTRABEAM® Spherical Applicators, K992577, K051055

Company: Device:

Hologic, Inc. MammoSite Radiation Therapy System, K011690, K091378

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- Intended Use

The INTRABEAM® System is intended to be used for radiation therapy treatment.

Indications for Use

The INTRABEAM® System is indicated for radiation therapy treatments. The INTRABEAM® Spherical Applicators are indicated for use with the INTRABEAM® System to deliver a prescribed dose of radiation to the treatment margin or tumor bed during intracavity and intraoperative radiotherapy treatments.

Device Description

TARGIT-A Trial

The modifications to the indications for use are supported by the publication, "Targeted intraoperative radiotherapy versus whole breast radiotherapy for breast cancer (TARGIT-A trial): an international, prospective, randomized, non-inferiority phase 3 trial", published by Vaidya, Joseph, Tobias et al. The study was published in The Lancet (Lancet 2010; 376: 71-72). The TARGIT-A trial was designed to test the hypothesis that in selected patients, substituting whole breast radiotherapy after breast-conserving surgery with targeted intraoperative radiotherapy (IORT) to the tumor bed would not lead to inferior local control of breast cancer. The randomly controlled study (N=2,232) was conducted by physicians around the world using the INTRABEAM System with Spherical Applicators as the only abbreviated partial breast irradiation (ABPI) device. The results of the trial demonstrate a non-significant rate of recurrence between the INTRABEAM Spherical Applicators versus whole breast radiation (1.2% versus 0.95%. p=0.41).

The study concluded that IORT treatment using INTRABEAM Spherical Applicators can be used in conjunction with whole breast radiotherapy.

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·Substantial Equivalence

Similar to the INTRABEAM System, the MammoSite Radiation Therapy System (RTS) provides a means of delivering radiation therapy in a tumor cavity. Both the MammoSite RTS and the INTRABEAM System with INTRABEAM Spherical Applicators are APBI technology and are comparable in target site and clinical usage.

The INTRABEAM Spherical Applicators that are the subject device for this 510(k) are equivalent to the currently marketed INTRABEAM Spherical Applicators in design, material, radiation doses and principles of operation. Based on the predicate devices and on the findings presented in the TARGIT-A trial publication, the INTRABEAM System with INTRABEAM Spherical Applicators is safe and effective with regards to the proposed indications for use.

Summary

As described in this 510(k) summary and based on the findings presented in the TARGIT-A trial publication, the INTRABEAM Spherical Applicators are safe and effective for their indications for use.

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Image /page/3/Picture/0 description: The image shows the text "DEPARTMENT OF HEALTH & HUMAN SERVICES". The text is in all caps and is in a bold, sans-serif font. The text is centered on the image and is the only element present. The background is plain white.

Public Health Service

December 27, 2012

Food and Drug Administration 10903 New Hampshire Avenue Document Control Center - WO66-G609 Silver Spring, MD 20993-002

Ms. Sarah Harrington Staff Regulatory Specialist Carl Zeiss Meditech, Inc. 5160 Hacienda Drive DUBLIN, CA 94568

Re: K121653 Trade/Device Name: INTRABEAM® System with INTRABEAM® Spherical Applicators Regulation Number: 21 CFR 892.5900 Regulation Name: X-ray radiation therapy system Regulatory Class: II Product Code: JAD Dated: December 17, 2012 Received: December 18, 2012

Dear Ms. Harrington:

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.

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. 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

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Page 2 - Ms. Sarah Harrington

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 out labeling regulation (21 CFR Parts 801 and 809), please contact the Office of In Vitro Diagnostics and Radiological Health at (301) 796-5450. 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 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/cdrh/industry/support/index.html.

Sincerely Yours,

Michael D. O'Hara

Janine M. Morris Director Division of Radiological Health Office of In Vitro Diagnostics and Radiological Health Center for Devices and Radiological Health

Enclosure

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Indications for Use

510(k) Number (if known): K121653

Device Name: INTRABEAM® System with INTRABEAM® Spherical Applicators

Indications for Use:

Prescription Use (Part 21 CFR 801 Subpart D) AND/OR

Over-The-Counter Use (21 CFR 807 Subpart C)

(PLEASE DO NOT WRITE BELOW THIS LINE-CONTINUE ON ANOTHER PAGE IF NEEDED)

Concurrence of CDRH, Office of In Vitro Diagnostics and Radiological Health (OIR)

Michael D. O'Hara

(Division Sign Off) Division of Radiological Health Office of In Vitro Diagnostic and Radiological Health

510(k)

Page 1 of

Regulation Number and Section

§ 892.5900 X-ray radiation therapy system.

(a)
Identification. An x-ray radiation therapy system is a device intended to produce and control x-rays used for 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.