The Invisalign System consists of a series of doctor-prescribed, thin, clear plastic removable orthodontic appliances (aligners) and proprietary 3-D software. The aligners gently move the patient's teeth in small increments from their original state to a more optimal, treated state. The Invisalign System is intended as an alternative to conventional wire/bracket technology and fixed appliances for the treatment of patients with malocclusion.

The proprietary Invisalign System 3-D software generates the image of a final, treated state and then interpolates a series of images that represent intermediate teeth states. The dental practitioner then reviews these images to depict, edit, view, monitor, and approve an orthodontic treatment plan. The dental practitioner has the option to reject or request modifications to the set-up prior to approving it for aligner fabrication. Once the doctor approves the set-up, the series of custom-made aligners are then manufactured, packaged, and shipped to the dental practitioner to be dispensed to the patient for treatment.

AI/ML Overview

The provided document is a 510(k) K143630 substantial equivalence determination for the Invisalign System, specifically focusing on modifications to its 3-D software. It does not provide detailed acceptance criteria and a study proving the device meets them in the way one might find in a full clinical trial report or a performance study for a diagnostic device.

However, based on the information provided, here's a breakdown of what can be extracted regarding acceptance criteria and the study:

1. Table of Acceptance Criteria and Reported Device Performance

The core of the "study" described here is a comparison to a predicate device (K081960). The acceptance criteria, implicitly, are that the modified Invisalign System (K143630) performs equivalently to the predicate device, especially considering the changes made to the software's functionality and platform.

The document states:

"The acceptance criteria were established in order to demonstrate the modified Invisalign System is substantially equivalent to the primary predicate device."
"Therefore, the results of this testing demonstrate the modified Invisalign System 3-D software is substantial equivalent to the primary predicate 3-D software."

Implicit Acceptance Criteria from Predicate Comparison (Table 4 of the document):

Characteristic	Predicate Device (K081960) Performance	Modified Device (K143630) Performance	Acceptance Criteria Met?
Intended Use Statement	"The Invisalign System is indicated for the alignment of teeth during orthodontic treatment of malocclusion."	"The Invisalign System is indicated for the alignment of teeth during orthodontic treatment of malocclusion."	Yes (Same)
3-D Software Description	Uses PVS impression or digital scan to generate final, treated state image, interpolates intermediate states, allows dental practitioner review/modification/approval, converts files for aligner fabrication.	Uses PVS impression or digital scan to generate final, treated state image, interpolates intermediate states, allows dental practitioner review/modification/approval, converts files for aligner fabrication.	Yes (Same)
Mode of Operation for 3-D Software	Produces 3D-model file, identifies teeth for repositioning, creates treatment plan (3-D models), allows dental practitioner review/modification/approval via ClinCheck.	Produces 3D-model file, identifies teeth for repositioning, creates treatment plan (3-D models), allows dental practitioner review/modification/approval via ClinCheck.	Yes (Same)
Elements of ClinCheck Software (Electronic Prescription Form)	Depicts, edits, views, monitors, and approves an orthodontic treatment plan.	Depicts, edits, views, monitors, and approves an orthodontic treatment plan.	Yes (Same)
Treatment Plan File Storage/Access	Downloads and stored on desktop/laptop computer.	Downloads to other computing devices (e.g., tablets), deleted upon exiting application. Comparison notes: "The Treatment Plan File is not downloaded and saved on desktop/laptop for K143630 as it is downloaded to a tablet and deleted upon exiting the application."	Yes (Functionally Equivalent in purpose, different mechanism deemed safe)
Tool Bar and Buttons	Includes Rotate/Translate, PAST, OCCLUS, View Attachment, Number, IPR, etc.	Includes Attachment, Number, IPR, etc. Comparison notes: "The following are not available on Subject Device tool Bar: Rotate/Translate, PAST, OCCLUS, and View"	Yes (Functionally Equivalent with text comments for missing features)
Menu Bar	Includes File, View, Export, Tools, Movie, Printing, Help, etc.	Includes File, View, Export, Tools, Help, etc. Comparison notes: "Subject Device is same as predicate device, but without Movie and Printing"	Yes (Functionally Equivalent with text comments for missing features)
Animation Controls	Includes Display, Play/Stop, Step Forward, Step Backward, etc.	Includes Play/Stop, Step Forward, and Step Backward. Comparison notes: "Subject Device controls are limited to: Play/Stop, Step Forward, and Step Backward"	Yes (Functionally Equivalent)
Viewing Options Toolbar	Includes grid, superimposition, basic buttons, etc.	Includes grid, superimposition, basic buttons, etc.	Yes (Equivalent)
Using Text Comments	Supported.	Supported.	Yes (Equivalent)
3-D Modification Mode (3-D Controls)	Present.	Absent. Comparison notes: "Not available in the Subject Device"	Yes (Functionally Equivalent with text comments for missing features)
Advanced Software Features (Bolton Analysis, Movie/Screenshot gen.)	Present.	Absent. Comparison notes: "Not available in the Subject Device"	Yes (Functionally Equivalent with text comments for missing features)
Minimum Hardware Requirements	Intel® Core™ i5, 4 GB RAM, 2 GB free disk space; Graphics card: Intel HD Graphics; Windows 7, 32 bit; Internet Explorer 11, Chrome, Firefox, Edge.	iPad 2 with iOS 8 or higher; 16 GB storage or more. Android 4.1.2 or higher; 16 GB storage or more. Comparison notes: "Subject Device is not used on a laptop/desktop computer as it operates on a tablet."	Yes (Different platform, deemed safe and effective for intended use)

Reported Device Performance:
The document explicitly states: "Results of verification and validation testing demonstrate the Invisalign System showed conformity with pre-established specifications and acceptance criteria." And further, "Therefore, the results of this testing demonstrate the modified Invisalign System 3-D software is substantial equivalent to the primary predicate 3-D software."

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

The document does not specify a "test set" in terms of patient data or specific clinical cases with a numerical sample size. The testing appears to be focused on software verification and validation against pre-established specifications and the predicate device's functionality, rather than a clinical performance study using a sample of patient data.

Test Set Sample Size: Not specified as a numerical sample of clinical cases or patient data. The testing described is software V&V.
Data Provenance: Not applicable as the testing described is primarily software engineering verification and validation, not a clinical study on patient data.

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

Since the "test set" and "ground truth" are framed around software functionality and substantial equivalence to a predicate, rather than a diagnostic accuracy claim, the document does not mention experts establishing ground truth in the typical clinical sense. The "ground truth" for the software's functionality would have been its design specifications and comparison to the predicate's known functionality.

Number of Experts: Not specified.
Qualifications of Experts: Not specified.

4. Adjudication Method for the Test Set

Not applicable as it's not a clinical study requiring adjudication of expert opinions on patient cases.

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

No, an MRMC comparative effectiveness study is not mentioned. The study described is a software verification and validation, and a comparison against a predicate device for substantial equivalence. It does not evaluate how human readers (dental practitioners) improve with or without AI assistance from this specific version of the software.

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

The device explicitly includes a "human-in-the-loop" aspect: "The dental practitioner then reviews these images to depict, edit, view, monitor, and approve an orthodontic treatment plan." The software generates the plan, but the practitioner approves or modifies it. Therefore, a standalone algorithm-only performance assessment in a vacuum is not the design or intent of this system's approval. The focus is on the software supporting the practitioner's workflow.

7. The Type of Ground Truth Used

The "ground truth" for this submission appears to be related to the functional specifications of the software and the established performance/functionality of the predicate device (K081960). The modified software met its design specifications and was deemed functionally equivalent for its intended use, despite some differences in feature implementation and platform. The safety and effectiveness are established by comparison to the predicate and the documented V&V of the modified software.

8. The Sample Size for the Training Set

The document does not describe a "training set" in the context of machine learning model development. This submission is for an updated version of an existing software system, not the initial development or a new AI model requiring a distinct training phase to learn from data.

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

Not applicable, as a training set, in the machine learning sense, is not described.

Summary

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Image /page/0/Picture/1 description: The image shows the logo for the U.S. Department of Health & Human Services. The logo is a circular seal with the words "DEPARTMENT OF HEALTH & HUMAN SERVICES - USA" around the perimeter. Inside the circle is an abstract symbol of three human profiles facing to the right, stacked on top of each other.

Food and Drug Administration 10903 New Hampshire Avenue Document Control Center - WO66-G609 Silver Spring, MD 20993-0002

November 18,2015

ALIGN TECHNOLOGY, INC. Margaret Anderson, Sr. Regulatory Affairs Analyst 2560 Orchard Parkway, San Jose, CA 95131 US

Re: K143630

Trade/Device Name: Invisalign System Regulation Number: 21 CFR 872.5470 Regulation Name: Orthodontic plastic bracket Regulatory Class: Class II Product Code: NXC Dated: October 20, 2015 Received: October 21, 2015

Dear Ms. Anderson:

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. 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

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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 [SELECT ONE: Part 801 [or, for IVDs only] Parts 801 and 8091); medical device reporting of medical 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 our labeling regulation (21 CFR Part 801), please contact the Division of Industry and Consumer Education at its toll-free number (800) 638-2041 or (301) 796-7100 or at its Internet address

http://www.fda.gov/MedicalDevices/Resourcesfor You/Industry/default.htm. Also, please note the regulation entitled, "Misbranding by reference to premarket notification" (21CFR 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 Industry and Consumer Education at its toll-free number (800) 638-2041 or (301) 796-7100 or at its Internet address

http://www.fda.gov/MedicalDevices/ResourcesforYou/Industry/default.htm.

Sincerely yours,

Susan Runno DDS, MA

Erin I. Keith, M.S. Director Division of Anesthesiology, General Hospital, Respiratory, Infection Control and Dental Devices Office of Device Evaluation Center for Devices and Radiological Health

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Indication for Use Statement

510(k) Number (if known): K143630

Device Name:

Invisalign System

Indications for Use:

The Invisalign System is indicated for the alignment of teeth during orthodontic treatment of malocclusion.

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

Concurrence of CDRH, Office of Device Evaluation (ODE)

Prescription Use _____________________________________________________________________________________________________________________________________________________________

Over-the Counter Use _________________________________________________________________________________________________________________________________________________________

(Per 21 CFR 801.109)

(Optional Format 1-2-96)

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K143630 510(k) Summary

Date Prepared: November 18, 2015

Applicant Information:

Align Technology, Inc. 2560 Orchard Parkway San Jose, CA 95131

Contact Person:	Margaret Anderson
Phone Number:	(408) 470-1410
Fax Number:	(408) 470-1011

Device Information:

Classification:	Class II
Trade Name:	Invisalign System
Common Name:	Aligner, Sequential
Classification Name:	Orthodontic plastic bracket (21 CFR 872.5470)

Device Description:

Intended Use:

The Invisalign System is indicated for the alignment of teeth during orthodontic treatment of malocclusion.

Equivalent Device:

The modified Invisalign System is substantially equivalent in intended use and/or method of operation to the Invisalign System (K081960). A comparison of the current and modified Invisalign System demonstrates that the device is substantially equivalent in terms of technology and performance characteristics.

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Characteristic	Invisalign System 3-D Software(K081960) Primary Predicate Device	Modified Invisalign System 3-D Software - (K143630)Subject Device	Comparison
Intended UseStatement	The Invisalign System is indicated for thealignment of teeth during orthodontic treatment ofmalocclusion.	The Invisalign System is indicated for the alignment ofteeth during orthodontic treatment of malocclusion.	Subject Device is the same aspredicate device.
3-D SoftwareDescription	The Align 3-D Software uses a scan of a PVSimpression or a digital scan (which represents anuntreated state) to generate the image of a final,treated state and then interprets a series of imagesthat represent intermediate teeth states. The dentalpractitioner then reviews these images and has theoption to reject or request modifications to the set-up prior to approving it for aligner fabrication.Once the dental practitioner approves the treatmentplan, the software converts the files to produce theseries of custom-made aligners.	The Align 3-D Software uses a scan of a PVS impressionor a digital scan (which represents an untreated state) togenerate the image of a final, treated state and theninterprets a series of images that represent intermediateteeth states. The dental practitioner then reviews theseimages and has the option to reject or requestmodifications to the set-up prior to approving it foraligner fabrication. Once the dental practitionerapproves the treatment plan, the software converts thefiles to produce the series of custom-made aligners	Subject Device is the same aspredicate device.
Mode ofOperation for 3-D Software	Invisalign system 3-D software performs thefollowing operations:• Produce 3D-model file of the PVS impressionor digital scan.• Identifies the individual teeth that will requiretreatment (i.e., repositioning).• Creates a treatment plan (i.e., 3-D models thatrepresent the treatment plan). The treatingdental practitioner reviews these images usingClinCheck software and has the option to rejector request modifications to the set-up prior toapproval.	Invisalign system 3-D software performs the followingoperations:• Produce 3D-model file of the PVS impression or digitalscan.• Identifies the individual teeth that will require treatment(i.e., repositioning).• Creates a treatment plan (i.e., 3-D models that representthe treatment plan). The treating dental practitionerreviews these images using ClinCheck software and hasthe option to reject or request modifications to the set-upprior to approval.	Subject Device is the same aspredicate device.
Elements ofClinCheckSoftware	An electronic prescription form and process usedto depict, edit, view, monitor and approve anorthodontic treatment plan.	An electronic prescription form and process used todepict, edit, view, monitor and approve an orthodontictreatment plan.	Subject Device is the same aspredicate device.
Elements ofClinCheckSoftware	Treatment Plan File:• The plan downloads to a dental practitioner's	Treatment Plan File:• The plan downloads to other computing devices (e.g.,	The Treatment Plan File is notdownloaded and saved on
Characteristic	Invisalign System 3-D Software(K081960) Primary Predicate Device	Modified Invisalign System 3-D Software - (K143630)Subject Device	Comparison
(continued)	desktop/laptop computer• The plan is stored on dental practitioner'sdesktop/laptop computer	tablets)• The plan is deleted upon exiting application	desktop/laptop for K143630 asit is downloaded to a tablet anddeleted upon exiting theapplication.
	Tool Bar and Buttons (e.g., Rotate/Translate,PAST, OCCLUS, View Attachment, Number, IPR,etc.)	Tool Bar and Buttons (e.g., Attachment, Number, IPR,etc.)	The following are not availableon Subject Device tool Bar:Rotate/Translate, PAST,OCCLUS, and View
	Menu Bar (e.g., File, View, Export, Tools, Movie,Printing, Help, etc.)	Menu Bar (e.g., File, View, Export, Tools, Help, etc.)	Subject Device is same aspredicate device, but withoutMovie and Printing
	Animation Controls (e.g., Display, Play/Stop, StepForward, Step Backward, etc.)	Animation Controls: Play/Stop, Step Forward, and StepBackward	Subject Device controls arelimited to: Play/Stop, StepForward, and Step Backward
	Viewing options toolbar (e.g., grid, superimposition,basic buttons, etc.)	Viewing options toolbar (e.g., grid, superimposition,basic buttons, etc.)	Subject Device is equivalentto predicate device.
	Using text comments	Using text comments	Subject Device is equivalentto predicate device.
	3-D modification mode (3-D Controls)	Absent	Not available in the SubjectDevice
	Advanced Software Features (e.g., Bolton Analysis,Movie generation and Screenshot generation, etc.)	Absent	Not available in the SubjectDevice
MinimumHardwareRequirements	• Intel® Core™ i5, 4 GB RAM, 2 GB free diskspace; Graphics card: Intel HD Graphics;Windows 7, 32 bit; Internet Explorer 11, Chrome,Firefox, Edge	• iPad 2 with iOS 8 or higher; 16 GB storage or more• Android 4.1.2 or higher; 16 GB storage or more	Subject Device is not used on alaptop/desktop computer as itoperates on a tablet.

Align Technology, Inc.

CONFIDENTIAL

Section 10 - Page 3 of 5

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The Indication for Use of the modified Invisalign System is the same as the currently marketed device. Also, as supported by the risk analysis and software testing, the minor difference between the modified Invisalign System and the currently marketed device (e.g., downloading ClinCheck to other computing devices) does not raise any new issues of safety and effectiveness. The ease-of-use, communication features that are not available in ClinCheck Mobile (e.g., 3D Controls, Bolton Analysis, Movie generation and Screenshot generation, etc.) can all be performed using text comments. Thus, the currently marketed, predicate device (K081960) and the modified Invisalign System are substantially equivalent.

Test Results:

Results of verification and validation testing demonstrate the Invisalign System showed conformity with pre-established specifications and acceptance criteria. The acceptance criteria were established in order to demonstrate the modified Invisalign System is substantially equivalent to the primary predicate device. Therefore, the results of this testing demonstrate the modified Invisalign System 3-D software is substantial equivalent to the primary predicate 3-D software. Software testing was conducted in accordance with "General Principles of Software Validation: Final Guidance for Industry and FDA Staff", 01/11/2002 and IEC 62304:2006 "Medical Device Software - Software Life-Cycle Processes".

Conclusion:

Based on the intended use and performance information provided in this notification, the modified Invisalign System has been shown to be substantially equivalent to the currently marketed predicate device.

Regulation Number and Section

§ 872.5470 Orthodontic plastic bracket.

(a)
Identification. An orthodontic plastic bracket is a plastic device intended to be bonded to a tooth to apply pressure to a tooth from a flexible orthodontic wire to alter its position.(b)
Classification. Class II.