K Number

Device Name

aBSI

Manufacturer

EXINI Diagnostics AB

Date Cleared

2019-08-05

(87 days)

Product Code

LLZ

Regulation Number

892.2050

Intended Use

aBSI is intended to be used by trained healthcare professionals and researchers for acceptance, transfer, storage, image display, manipulation, quantification and reporting of digital medical images acquired using nuclear medicine (NM) imaging. The device provides general Picture Archiving and Communications System (PACS) tools as well as a clinical application for oncology including lesion marking and quantitative analysis.

Device Description

The aBSI is a software-only medical device that provides a fully quantitative assessment of a patient's skeletal disease on a bone scan, as the fraction of the total skeleton weight. The user of this product is typically a health-care professional using the software to view the patient images and analysis results.

More Information

Contact

Type

Center

Panel

Date Received

Product Code

Subsequent Product Codes

Applicant Name (Manufacturer)

Device Name

Decision

Street 1

Street 2

City

State

Country Code

ZIP

Postal Code

Class Advise Committee

SSP Indicator

Third Party Reviewed

Expedited Review

Predicate Devices

K122205

Reference Devices

K122205

AI/ML (Artificial Intelligence / Machine Learning)

No
The summary does not mention AI, ML, deep learning, or any related terms. The description focuses on quantitative assessment and standard image processing tools. The performance studies describe analytical validation and clinical studies comparing the device to a predicate and PCWG criteria, without mentioning training or testing of AI/ML models.

Therapeutic

No
The device provides tools for image display, manipulation, quantification, and reporting, focusing on analysis rather than direct treatment or therapy.

Diagnostic

Yes

The device aids in the quantification and analysis of patient skeletal disease from nuclear medicine images, providing information used by healthcare professionals to assess a patient's condition.

SaMD (Software as a Medical Device)

Yes

The device description explicitly states "The aBSI is a software-only medical device".

IVD (In Vitro Diagnostic)

Based on the provided information, this device is not an In Vitro Diagnostic (IVD).

Here's why:

IVDs analyze biological samples: IVDs are designed to examine specimens taken from the human body, such as blood, urine, tissue, etc., to provide information about a person's health.
This device analyzes medical images: The aBSI processes and analyzes digital medical images acquired from nuclear medicine imaging. It does not directly interact with or analyze biological samples.
The intended use is image processing and analysis: The description clearly states the device is for "acceptance, transfer, storage, image display, manipulation, quantification and reporting of digital medical images." While it provides quantitative analysis of skeletal disease, this analysis is performed on the image data, not on a biological sample.

Therefore, the aBSI falls under the category of a medical image processing and analysis software device, not an In Vitro Diagnostic.

PCCP (Predetermined Change Control Plan) Authorized

N/A

Overview

Intended Use / Indications for Use

Product codes

LLZ

Device Description

Mentions image processing

Yes

Mentions AI, DNN, or ML

Not Found

Input Imaging Modality

nuclear medicine (NM) imaging

Whole body bone scans
SPECT

Anatomical Site

skeleton / skeletal disease

Indicated Patient Age Range

Not Found

Intended User / Care Setting

Trained healthcare professionals and researchers.
Health care clinics.

Description of the training set, sample size, data source, and annotation protocol

Not Found

Description of the test set, sample size, data source, and annotation protocol

Study I:

Sample Size: 721 patients evaluable with aBSI out of 1245 enrolled.
Data Source: A multi-site study phase III (NTC 01234311) involving patients with metastatic castration-resistant prostate cancer (mCRPC). Study subjects were recruited at 241 sites in 37 countries (including the US).
Annotation Protocol: Not explicitly detailed, but involved automated BSI calculation and association with overall survival, progression free survival, and opioid induced survival.

Study II:

Sample Size: 169 patients had bone scans available for aBSI analysis out of 257 assessed.
Data Source: Retrospective study at Memorial Sloan Kettering Cancer Center (MSKCC) – single site, involving patients with metastatic prostate cancer (mCRPC) enrolled in Phase II/II clinical trials of agents targeting the androgen receptor (AR) signaling axis.
Annotation Protocol: Not explicitly detailed, but involved comparison of aBSI increase against counting number of new lesions (by PCWG criteria) in radiographic progression.

Summary of Performance Studies (study type, sample size, AUC, MRMC, standalone performance, key results)

Bench Testing:

Study Type: Analytical validation studies
Sample Size: Not specified
Key Results:
- Linearity & Accuracy of BSI calculation
- Precision of BSI calculation
- Reproducibility with different cameras
- Reproducibility with multiple images
- Patient study to demonstrate Reproducibility of BSI calculation with Repeated Bone Scans
- Comparison testing using a phantom simulation to compare the bone scan index determined with predicate EXINI 1.7 to that the subject device aBSI.

Clinical Data:
Study I: Phase 3 validation of the automated Bone Scan Index association with overall survival in men with metastatic castration-resistant prostate cancer

Study Type: Prospective Planned Analysis – A multi-site study phase III
Sample Size: 721 Prostate Cancer patients
Key Results: Automated BSI (median=1.07; range: 0-32.60) was significantly associated with OS (HR:1.20; 95%CI:1.14-1.26; P

Regulation Number and Section

§ 892.2050 Medical image management and processing system.

(a)
Identification. A medical image management and processing system is a device that provides one or more capabilities relating to the review and digital processing of medical images for the purposes of interpretation by a trained practitioner of disease detection, diagnosis, or patient management. The software components may provide advanced or complex image processing functions for image manipulation, enhancement, or quantification that are intended for use in the interpretation and analysis of medical images. Advanced image manipulation functions may include image segmentation, multimodality image registration, or 3D visualization. Complex quantitative functions may include semi-automated measurements or time-series measurements.(b)
Classification. Class II (special controls; voluntary standards—Digital Imaging and Communications in Medicine (DICOM) Std., Joint Photographic Experts Group (JPEG) Std., Society of Motion Picture and Television Engineers (SMPTE) Test Pattern).

Summary

August 5, 2019

Image /page/0/Picture/1 description: The image shows the logo of the U.S. Food and Drug Administration (FDA). The logo consists of two parts: the Department of Health & Human Services logo on the left and the FDA logo on the right. The FDA logo features the letters "FDA" in a blue square, followed by the words "U.S. FOOD & DRUG ADMINISTRATION" in blue text.

EXINI Diagnostics AB % Donna-Bea Tillman, Ph.D. Senior Consultant Biologics Consulting Group, Inc. 1555 King Street. Suite 300 ALEXANDRIA VA 22314

Re: K191262

Trade/Device Name: aBSI Regulation Number: 21 CFR 892.2050 Regulation Name: Picture archiving and communications system Regulatory Class: Class II Product Code: LLZ Dated: May 9, 2019 Received: May 10, 2019

Dear Dr. Tillman:

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.

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-reportingcombination-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 mediation-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.

For

Thalia T. Mills, Ph.D. Director Division of Radiological Health OHT7: Office of In Vitro Diagnostics and Radiological Health Office of Product Evaluation and Quality Center for Devices and Radiological Health

Enclosure

Indications for Use

510(k) Number (if known) K191262

Device Name aBSI

Indications for Use (Describe)

Type of Use (Select one or both, as applicable)

☑ Prescription Use (Part 21 CFR 801 Subpart D)
☐ Over-The-Counter Use (21 CFR 801 Subpart C)

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In accordance with 21 CFR 807.87(h) and (21 CFR 807.92) the 510(k) Summary for the aBSV is provided below.

SUBMITTER 1.

Applicant: EXINI Diagnostics AB Ideon Science Park Scheelevägen 27 223 70 Lund Sweden Aseem Anand, Ph.D. Contact: Vice President EXINI Diagnostics AB Ideon Science Park, Scheelevägen 27, SE-223 70 Lund, Sweden Tel: +46706604084 aseem.anand@exini.com Donna-Bea Tillman, Ph.D. Submission Correspondent: Senior Consultant Biologics Consulting 1555 King Street, Suite 300 (410) 531-6542 dtillman(@biologicsconsulting.com

2. DEVICE

Date Prepared:

Device Trade Name:	aBSI
Device Common Name:	Picture Archiving and Communications System
(PACS)
Classification Name	21 CFR 892.2050 System, Image Processing,
Radiological
Regulatory Class:	II
Product Code:	LLZ

May 9, 2019

3. PREDICATE DEVICE

Predicate Device: EXINI (K122205) K191262

DEVICE DESCRIPTION 4.

INTENDED USE/INDICATIONS FOR USE ನ.

SUBSTANTIVE EQUIVALENCE 6.

Comparison of Indications

The image modality computed tomography (CT) has been removed from the intended use for aBSI compared to EXINI. The ability to also display CT images was a feature introduced in EXINI to allow for simultaneous viewing of both types of images. CT images are not required or used for BSI calculation and this feature was rarely used. Therefore, this feature has been removed and CT images are not accepted by the aBSI device. This change does not affect the fundamental intended use of the device, and EXINI can be used as a predicate for aBSI.

Technological Comparisons

The table below compares the key technological features of the subject devices to the predicate device

	EXINI (predicate device)	aBSI (subject device)	Discussion of Differences
Intended user	Health care professionals and
researchers	Same	-
Intended use
environment	Health care clinics	Same	-
Classification	System, Image Processing,
Radiological (LLZ)
21 CFR 892.2050	Same	-
Installation	Product CDs or downloadable
installation files	Cloud-based service and
access with personal log-in.	Does not affect the clinical
use of the device
Operating system	Microsoft Windows	Microsoft Windows or
macOS with Chrome browser	Does not affect the clinical
use of the device
	EXINI (predicate device)	aBSI (subject device)	Discussion of Differences
DICOM
compatibility	DICOM 3:
• Whole body bone scans
• Static (partial) bone scans
• SPECT/CT	DICOM 3:
• Whole body bone scans
• SPECT	Static (partial) bone scans
and CT images are not
required or used for BSI
calculation.
Image upload	Via DICOM SCP or folder on
local computer or network	Via folder on local computer
or network	Does not affect the clinical
use of the device
Support for
multiple Bone
Scans	Yes, if multiple scans are
provided, the images are
automatically aligned vertically	Same	-
Colormaps	A selection of commonly used
colormaps	Sub-Selection of previously
provided colormaps.	Optimal colormaps
continue to be provided
Zoom	Manually adjustable image size
Zoom	Automatically adjusted image
size
Zoom	To improve the efficiency
of aBSI automatic
adjustment of images to
screen size
Windowing	• Automatic adjustment of
maximum and minimum
thresholds for image windowing
• Manual adjustment of
maximum and minimum
thresholds	• Automatic adjustment of
maximum and minimum
thresholds for image
windowing (same)
• Manual adjustment of
maximum and minimum
thresholds has a wider range	Both devices show
normalized images at
startup and have
adjustable min and max
thresholds for image
windowing.
Intensity display	Local intensity displayed at
mouse pointer when hovering
over image	Local intensity displayed in
left corner of the image when
hovering over image	To improve visibility of
the intensity
Image layouts	• Anterior and posterior images
shown side by side
• Mirror tool for switching
between the anterior and
posterior image in the same
image frame	• Anterior and posterior
images shown side by side	Removal of feature does
not impact clinical utility
of the device
Image Quality
Control	• Total image intensity
displayed
• Skeletal image count
displayed	• Total image intensity
displayed	Both devices display total
image intensities. Total
image intensity is the
common way of assessing
image quality, therefore
total skeletal intensity is
not needed.
Hotspot display	• Hotspots displayed in image
• Hotspot involvements are
displayed in tables. One table
per scan.	• Hotspots displayed in image	Both devices display
hotspots in the images.
	EXINI (predicate device)	aBSI (subject device)	Discussion of Differences
Segmentation of
skeletal atlas	Segmentation of skeletal atlas
covering the area from the skull
down to ¾ of the femur and
humerus.	Segmentation refined, and
skeletal area covered by the
atlas increased to cover the
entire femur and humerus.	Allows for detection of
hotspots further out in the
limbs.
Normalization	Images are normalized so that
healthy bone tissue intensities
are automatically set to a
predefined level.	Same	-
Hotspot detection	Algorithm to detect high
intensity regions of interest
within the skeletal atlas.	Improved algorithm to detect
of high intensity regions of
interest within the skeletal
atlas.	Results of clinical
performance testing
demonstrate substantially
equivalent performance.
Summary page
export	Supported	Supported	-
CSV export	N/A	Supported	This feature was
implemented to facilitate
aBSI use in research
studies.

Technological Comparison Table 1:

The EXINI was cleared in 2012 with BSI quantification as an integral feature. Since its clearance, the device algorithm has evolved, and the device is now hosted in cloud infrastructure. However, the essential BSI quantification feature of the device remained substantially equivalent.

PERFORMANCE DATA 7.

Biocompatibility Testing

There are no direct or indirect patient-contacting components of the subject device. Therefore, patient contact information is not needed for this device.

Electrical safety and electromagnetic compatibility (EMC)

Not applicable. The subject device is a software-only device. It contains no electric components, generates no electrical emissions, and uses no electrical energy of any type.

Software Verification and Validation Testing

Software verification and validation testing were conducted and documentation was provided as recommended by FDA's Guidance for Industry and FDA Staff, "Guidance for the Content of Premarket Submissions for Software Contained in Medical Devices." The software for this device was considered as a moderate level of concern because, although unlikely, an incorrect BSI value could potentially contribute to the risk of an incorrect therapy decision or delay in the delivery of appropriate care.

Bench Testing

EXINI Diagnostics conducted verification to demonstrate the performance of the device, including:

. A set of analytical validation studies to evaluate the performance of the aBSI v3.4 in quantifying bone scans, including:
- Linearity & Accuracy of BSI calculation o
- Precision of BSI calculation O
- Reproducibility with different cameras O
- o Reproducibility with multiple images
Patient study to demonstrate Reproducibility of BSI calculation with Repeated Bone Scans
Comparison testing using a phantom simulation to compare the bone scan index determined with predicate EXINI 1.7 to that the subject device aBSI.

Animal Testing

Not applicable. Animal studies are not necessary to establish the substantial equivalence of this device.

Clinical Data

Results from the two clinical studies comparing aBSI assessment to standard interpretation of bone scan demonstrated the utility of aBSI device against the state of the art (PCWG criteria) and essential clinical outcomes.

| Study

Number	Title	Objective	Design	Patients
I	Phase 3 validation of the
automated Bone Scan Index
association with overall
survival in men with metastatic
castration-resistant prostate
cancer	Association of aBSI with
clinical outcome –
overall survival,
progression free survival,
opioid induced survival	Prospective Planned
Analysis – A multi-site
study phase III: NTC
01234311	Prostate
Cancer
(N=721)
II	Optimizing Radiographic
Progression Free Survival by
Prostate Cancer Working
Group (PCWG) Criteria using
the Automated Bone Scan
Index ( aBSI )	Comparison of aBSI
increase against counting
number of new lesions
(by PCWG criteria) in
radiographic progression	Retrospective study at
Memorial Sloan Kettering
Cancer Center – single site	Prostate
Cancer
(N=169)

Study I involved a prospectively defined analysis of patients in a phase 3 international, multicenter study. This phase 3 study was a multicenter randomized, double-blind, placebocontrolled study of tasquinimod (10TASQ10) in metastation-resistant prostate cancer mCRPC patients. Study subjects were recruited at 241 sites in 37 countries (including the US).

Of the total 1245 phase 3 patients enrolled in 37 countries, 721 patients were evaluable with aBSI. The aBSI population was representative of the total study population based on baseline characteristics. Automated BSI (median=1.07; range: 0-32.60) was significantly associated with OS (HR:1.20; 95%CI:1.14-1.26; P