March 4, 2022

Pearl Inc.
℅ Zvi Ladin, Ph.D.
Principal
Boston MedTech Advisors
990 Washington Street, Suite #204
Dedham MA 02026

Re: K210365
Trade/Device Name: Second Opinion®
Regulation Number: 21 CFR 892.2070
Regulation Name: Medical Image Analyzer
Regulatory Class: Class II
Product Code: MYN
Dated: January 20, 2022
Received: January 24, 2022

Dear Zvi Ladin:

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.

U.S. Food & Drug Administration

10903 New Hampshire Avenue Doc ID# 04017.04.32
Silver Spring, MD 20993
www.fda.gov
K210365 - Zvi Ladin Page 2

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 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-reporting-
combination-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-devices/medical-device-safety/medical-device-reporting-
mdr-how-report-medical-device-problems.

For comprehensive regulatory information about medical devices and radiation-emitting products, including
information about labeling regulations, please see Device Advice (https://www.fda.gov/medical-
devices/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-devices/device-advice-comprehensive-regulatory-
assistance/contact-us-division-industry-and-consumer-education-dice) for more information or contact DICE
by email ([email protected]) or phone (1-800-638-2041 or 301-796-7100).

Sincerely,
Digitally signed by
Laurel M. Burk -S
Date: 2022.03.04
12:12:32 -05'00'
Laurel Burk
Assistant Director
Diagnostic X-ray Systems Team
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
Pearl, Inc.

510(K) SUMMARY K210365

1. Submitter's Identification
Pearl Inc.
2515 Benedict Canyon Dr.
Beverly Hills, CA, 90210
USA
(239) 450-8829

Contact Person: Bill Birdsall

Position: Chief Compliance Officer

Date Summary Prepared: March 2, 2022

2. Trade Name of the Device

Second Opinion®

3. Common or Usual Name

Analyzer, Medical Image

4. Classification Name, Regulatory Classification & Product Code

Classification Name: Analyzer, Medical Image
Regulatory Classification: 21CFR 892.2070, Class II
Product Code: MYN

5. Predicate Device Information

Predicate device: Logicon Caries Detection by Carestream Dental LLC. (P980025 &
Supplements 1, 2, 3 & 4)

6. Device Description
Second Opinion® is a computer aided detection ("CADe”) software device indicated for use
by dental health professionals as an aid in their assessment of bitewing and periapical
radiographs of permanent teeth in patients 12 years of age or older. Second Opinion®
employs computer vision technology, developed using machine learning techniques, to
detect and draw attention as second reader to regions on bitewing and periapical
radiographs where distinct pathologic and/or nonpathologic dental features may appear.

Page 1 of 10
Pearl, Inc.

Second Opinion® consists of three parts:

● In-office application or Client User Interface (“Client”)
● Application Programing Interface (“API”)
● Computer Vision Models (“CV Model”, “CV Models”)

The Client resides in the clinician’s office. The API and CV Models reside in a cloud
computing platform, where image processing takes place.

The CV Models create and append to a metadata file information denoting pixel regions
and other associated properties of each radiograph. Those associated properties include:

● Normal anatomy (e.g., Teeth)

● Nine radiological dental findings, which include five restorations (crowns, bridges,
implants, root canals, fillings) and four pathologies (caries, margin discrepancy –
MD, calculus, periapical radiolucency – PR)

The API delivers the metadata back to Second Opinion® via the cloud. The metadata
information is displayed in graphical form to clinical users by way of the Second Opinion®
Client’s user interface.

7. Indications for Use

Second Opinion® is a computer aided detection ("CADe”) software to identify and mark
regions in relation to suspected dental findings which include Caries, Discrepancy at the
margin of an existing restoration, Calculus, Periapical radiolucency, Crown (metal,
including zirconia & non-metal), Filling (metal & non-metal), Root canal, Bridge and
Implants.

It is designed to aid dental health professionals to review bitewing and periapical

radiographs of permanent teeth in patients 12 years of age or older as a second reader.

8. Summary of Substantial Equivalence:

The predicate device and candidate device are similar CADe devices in the following ways:

1) Intended use: Both devices are intended to be used to aid dental clinicians in their
detection of pathologic dental features in radiographs of permanent teeth.
2) Technology characteristics: Both devices employ computer vision and machine
learning to output detections.
3) Safety: As both the candidate and predicate device are CADe systems, neither pose
any direct safety hazard to the patient.
4) Clinical Performance: Both devices have undergone clinical studies which
demonstrate statistically significant improvement in aided reader performance.
However, due to technological differences (e.g., the need to mark the region of
interest by the user of the predicate device), there are challenges for a direct
technological and performance comparison with the predicate device.

Page 2 of 10
Pearl, Inc.

For substantial equivalence comparison, the follow table is provided:

Predicate Device:
Candidate device:
Item Logicon Caries Comments
Second Opinion®
Detection (P980025)
Manufacturer Pearl Inc. Carestream DentalLLC N/A

Classification 892.2070 892.2070 Same

Product Code MYN MYN Same (Productcode MYN
wasrecently
reclassified toclass II)
Image Modality Radiograph Radiograph Same
Intended Use To aid in clinical detection of To aid in clinical Same indication as
pathologic and/or non- detection of pathologic predicate device as both
pathologic dental features in features in devices are intended to
radiographs radiographs of adult teeth identify pathologic features
of permanent teeth, as a in dental radiographs.
second reader, only after the
initial read is completed
Indications for Second Opinion® is a The Logicon Caries
Use computer aided detection Detector is a software
("CADe”) software to device that is an aid in the
identify andmark regions in diagnosis of caries that
relation to suspected dental have penetrated into the
findings which include dentin, on un- restored
Caries, Discrepancy at the proximal surfaces of
margin of an existing secondary dentition
restoration, Calculus, through the statistical
Periapical radiolucency, analysis of digital intraoral
Crown (metal, including radiographic imagery. The
zirconia & non-metal), device provides additional
Filling (metal & non- metal), information for the
Root canal, Bridge and clinician to use in his/her
Implants.It is designed to diagnosis ofa tooth
aid dental health surface suspected of
professionals to review beingcarious. It is
bitewing and periapical designed to work in
radiographs of permanent conjunction with an
teeth in patients 12 years of existing Carestream
age or older as a second DentalRVG digital x-ray
reader. radiographic system with
Carestream Dental
Imaging Software
(DIS/CSI) for WINDOWS
7 or higher.

Page 3 of 10
Pearl Inc.

Intended body part Dental Dental Same as predicate device

Intended User Dental Clinicians Dental Clinicians Same aspredicate

device

Marker Bounding boxes / User may mark ROI with V

Type/Size Fixed tool (to select a pie-wedge
shape: narrow endat the
center of thetooth, wide
end extending through
surface over the
suspicious region)
or the pencil tool todraw
the ROIs.

Prescription For Prescription Use For Prescription Use Same

or OTC
Algorithm Utilizes computer vision Utilizes computer vision Same
neural network algorithms, neural networkalgorithms
developed from open-source developed using proprietary
models using supervised techniques.
machine learning
techniques.

Reader Second reader workflow The user can select specific

workflow regions of interest (ROI) to
be analyzed by the
program

Clinical Study Standalone study for • MRMC study for two All devices included
pathological (Caries, types of dental caries: MRMC studies to assess
discrepancy at the approximal/enamel into effectiveness.
margin, calculus, and dentin
periapical radiolucency) • Analysis included: ROC
and non-pathologic analysis for primary
feature detection endpoints
performance (Crowns,
fillings, rootcanal,
bridges, and Implants).
• Multiple-Reader,
Multiple-Case
(MRMC) study for
pathologic dental
features
• Analysis included:
• wAFROC-FOM
analysis for
primary endpoints
• Determination of
the changes in
sensitivity and
change in number
of false positive

Page 4 of 10
 Pearl Inc.

dental pathologies
of a given type per
image (FPPI).

Image Source Accepts image formats Limited to Different

from RVG, DICOM, Carestream
JPEG, TIFF, proprietary
and PNG and radiography
converts to JPEG. equipment.

Type of CADe CADe Same

Device
Hardware WINDOWS 7 or higher WINDOWS 7 or Same
Requirements higher
Analysis of digital Bitewing & Periapical Bitewing only Similar
intraoral
radiographic
imagery

Table 1. Comparison of Second Opinion® with the predicate device

9. Technological Comparison to Predicate Device

The fundamental technological principle for both the candidate and predicate devices is
theautomatic computerized lesion detection of the dental finding of interest, as an aid to
dental health professionals to review patients’ dental radiographs.

The candidate and predicate devices are technologically equivalent as follows:

• Both are software devices designed to run on Windows operating systems.

• Both devices are designed to process digital intraoral bitewing radiographs.
• Both devices use neural network-based computer vision algorithms for lesion
detection.
• Both devices demarcate detections within the user interface with a graphical
overlay on the radiograph.
• Both devices produce near-instantaneous detection results.
• Both devices are considered to be of “moderate” level of software concern.
• Both devices passed all verification and validation testing requirements.

The candidate and predicate devices are technologically different as follows:

• The candidate device includes computer vision algorithms capable of detecting other
dental features in addition to carious lesions.
• The candidate device includes computer vision algorithms capable of making
detections in periapical radiographs in addition to bitewing radiographs
• The candidate device uses a cloud-based rather than CD-ROM method of software
installation
• The candidate device is capable of making detections in images captured on

Page 5 of 10
 Pearl Inc.

radiography devices from a range of manufacturers, rather than in conjunction only

with a Carestream digital imaging device.
• The candidate device outputs detections as a second reader only and physician
needs to make final determinations. The user does not select specific regions of
interest (ROI) to be analyzed by the program
• The candidate device does not predict lesion depth or severity.

10. Assessment of Benefit-Risk, Safety and Effectiveness, and

Substantial Equivalence to Predicate Device:
Pearl has demonstrated the benefits of the device through a standalone and MRMC clinical
studies of aided and unaided reader accuracy across the four pathologic features includedin
Second Opinion®’s Indications for Use: caries, margin discrepancy, calculus, and periapical
radiolucency. While detection accuracy improvement between aided and undead readers
were seen to vary by pathologic feature, the results of the MRMC studiesshowed statistically
significant aided-reader improvement in detection accuracy across all four pathologic
features. When the probable benefits and probable risks of Second Opinion® are weighed
against one another, the weight of benefits significantly exceeds that of risks. This
judgement can be made based on review of the submitted materials showing that Second
Opinion® meets the design verification and validation and labeling Special Controls required
for clearance of Class II medical image analyzers. It is, thus, concluded that Second
Opinion® can be considered safe and effective such that the device will aid users in the
indicated user population in their radiographic detection of certain abnormal dental features.
11. Discussion of Non-Clinical Tests Performed
The device is a software-only device, so most testable characteristics common to other
device types, including Biocompatibility/Materials, Shelf Life/Sterility, Electromagnetic
Compatibility and Electrical Safety, Magnetic Resonance (MR) Compatibility, are not
applicable to this device.
Software Verification and Validation Testing
Second Opinion® verification testing of software, unit testing, software integration testing,
and software system testing were conducted. Verification and validation activities for
Second Opinion® were conducted to provide evidence that the design meets user needs,
intended use and application specification. The testing results support that all the software
specifications have met the acceptance criteria and the claims of substantial equivalence.
12. Discussion of Clinical Tests Performed
Clinical evaluation of Second Opinion® was performed to validate the clinical efficacy of the
system in helping dentists review four dental pathologies (caries, margin discrepancy,
calculus, and periapical radiolucency) on intra oral radiographs. Second Opinion® was
clinically tested as a standalone device and in a fully-crossed multi-reader multi-case
(MRMC) reader study.

The Weighted Alternative Free-Response Receiver Operating Characteristic (wAFROC)

paradigm was used as the metric of efficacy for all studies. The ground truth (GT) was
assessed using the consensus approach (based on agreement among at least three out of

Page 6 of 10
 Pearl Inc.

four expert readers). Each GT expert independently marked areas on any radiograph
wherein they marked (using the smallest possible rectangular bounding box to encompass
the entire region identified) and identified the pathologic and/or non-pathologic features. All
experts went through the training and reading of the images over the same period of time.
The studies were conducted as retrospective, unblinded open-label, multi-site trials that
produced clinically useful information on the potential application of this device in a dental
office setting. 2,010 images reviewed by all four GT readers were used for the standalone
and MRMC studies:

Feature Caries MD Calculus PR

# of normal radiographs 1,640 1,741 1,766 1,887

# of lesion-containing radiographs 370 269 244 123
Number of lesions 655 355 467 144
Average # of lesions/image 1.77 1.32 1.91 1.17

Table 2. Images reviewed by all four GT readers

Standalone Testing

In the standalone study, the Second Opinion® CADe exhibited comparable performance to
unaided readers in detecting four pathologic features and five restorations based on Jaccard
Index (JI) of ≥ 0.4 for LL (Lesion Localization). This value of JI optimized lesion localization
of unaided readers and was also used to process the Standalone performance of the
candidate device. Use of other values of JI will clearly affect the overall performance of the
product.

• Jaccard Index of 0.4 corresponds to an overlap area between the device’s outputs
and truth of 57% in theory. Using Jaccard Index of 0.4 leads to the device’s
standalone performance wAFROC-FOM 95% CI (0.73, 0.79), (0.71, 0.78), (0.78,
0.85) and (0.75,0.84) for Caries, MD, Calculus, and PR with consensus truthing
method, respectively.

• Jaccard Index of 0.5 corresponds to an overlap area between the device’s outputs
and truth of 67% in theory. Using Jaccard Index of 0.5 leads to the device’s
standalone performance wAFROC-FOM 95% CI (0.61, 0.68), (0.62, 0.68), (0.75,
0.81) and (0.69,0.78) for Caries, MD, Calculus, and PR with consensus truthing
method, respectively.

Product’s standalone sensitivity and false positive rate were also assessed. Sensitivity is
defined as the number of dental pathologies (of a given type) detected as a percentage of
the same type GT pathologies on a given slide. The false positive rate is defined as the
number of false positive findings of a given type identified on a given slide and expressed
in terms of FPPI (false positive per image).

Page 7 of 10
 Pearl Inc.

The standalone sensitivity of the product was in the range of 76.39% – 89.77% and the
false positive rate was in the range of 0.46 – 4.85.

MRMC Testing and Results

Pearl conducted a fully-crossed multi-reader, multi-case (MRMC) retrospective reader study
to determine the impact of Second Opinion® on reader performance in detecting fourdental
pathologies. The primary objective of the study was to determine whether the detection
accuracy of readers aided by Second Opinion® is superior to the detection accuracy of
readers unaided by Second Opinion®.

Twenty-five readers were asked to determine the locations of all identified (i.e., classified)
lesions, in a setting designed to increase user specificity in detection. Each reader reada
total of 2,010 images – 1,005 images unaided and 1,005 images aided (using Second
Opinion®).

The performance of readers aided by the use of Second Opinion® demonstrated statistically
significant improvement over the performance of unaided readers for caries, margin
discrepancy, calculus, and periapical radiolucency.

Moreover, the improvement in sensitivity of a single dental finding was in the range of 0.9%–
11.7% and examination of the individual improvement in sensitivity documented that:
• 17/25 (68%) improved the sensitivity of detecting Caries
• 19/25 (76%) improved the sensitivity of detecting MD
• 22/25 (88%) improved the sensitivity of detecting Calculus
• 25/25 (100%) improved the sensitivity of detecting PR
The improvement in false positive rate of a single dental pathology was in the range of
0.08 – 0.136. Examination of the individual improvements in the rate of FPPI documented
that:
• 23/25 (92%) improved the rate of FPPI for Caries
• 24/25 (96%) improved the rate of FPPI for MD
• 25/25 (100%) improved the rate of FPPI for Calculus
• 9/25 (36%) improved the rate of FPPI for PR
No statistically significant reductions in performance were observed when readers used
Second Opinion® as an assistive aid. All pathologies met the pre-specified endpoints for
the MRMC study.
The results have demonstrated that, in a significant portion of the target population,
detection performances using the proposed device improved with statistical significance.
Therefore, the proposed device could provide potential assistance for dentists in the reviewof
dental pathologies found in intra oral radiographs when used as a second read.

13. Comparison to Predicate Clinical Outcomes

Predicate Device: Logicon Caries Detection by Carestream Dental LLC.
The predicate device’s clinical study was based on a dataset of 175 tooth surfaces and

Page 8 of 10
 Pearl Inc.

18 readers. The primary endpoint was to determine the device’s effect on reader
sensitivity (true positive identification), specificity (true negative), and accuracy (fraction of
all correct diagnosis made by a dentist) as they pertain to detection of caries lesions into the
dentin on proximal tooth surfaces. Truth was defined as the dentist’s clinical assessment
of the exposed lesion prior to restoration. Results from this study showed a significant
increase in reader sensitivity and no significant change in reader specificity (slightly
reduced when aided by Logicon) when readers used the device. Average reader accuracy,
reported as the comparison of detection accuracy unaided readers to aided readers, were
determined using the ROC paradigm and showed an improvement of 12.8 percent:

Unaided Reader Accuracy Aided Readers Accuracy

0.756 0.883

Table 5. Logicon Caries Detector (predicate device) accuracy – Aided vs. Unaided
However, this observed median difference is not significant based on the Wilcoxon test
(P=0.0537). Therefore, the improvement in diagnostic accuracy associated with the
Logicon Caries device is mostly associated with the improvement in sensitivity.

The candidate device’s clinical study was based on a dataset of 2010 radiographs which
included 370 carious lesions. Three primary studies were performed: Standalone, MRMC,
and CADe vs. Reader. The endpoints were designed to determine the candidate device’s
ability to identify dental features as a standalone system and to determine the device’s
effect on reader performance.
In comparison to the predicate device’s clinical study, caries detection performance of the
candidate device, measured based on wAFROC-FOM, for unaided and Second Opinion®-
aided readers with Second Opinion® is:

Unaided Reader wAFROC-FOM Aided Reader wAFROC-FOM

0.740 0.758

Table 6. Second Opinion® wAFROC-FOM – Aided vs. Unaided

This difference is significant with P=0.0062.

Therefore, similar to the predicate device, the candidate device also demonstrated
improved detection accuracy in detecting carious lesions. Although candidate device
performance was determined using a different statistical paradigm (wAFROC) than
predicate device performance (ROC), the trend is the same: When aided by the device,
readers’ ability to detect carious lesions improves.

14. Conclusions
Based on the information presented above, Second Opinion® and its predicate device,
Logicon Caries Detector, are deemed to have similar intended uses as devices which aid in

Page 9 of 10
Pearl Inc.

the detection of pathologic features that can appear in dental radiographic imagery.
Second Opinion®’s clinical trial results demonstrate that like its predicate, the device
effectively improves the performance of its intended users,as a second read CADe system.
As Second Opinion® raises no new or different questions of safety or effectiveness,
performs in accordance with its specifications, meets user needs, meets the intended use
and therefore was found substantially equivalent to the predicate device.

Page 10 of 10