The subject device, Invisalign System with Pre-Formed Attachments (PFA) System, is a modification to the predicate device, the Invisalign System (K220287, cleared on April 7th, 2022). The Invisalign System with PFA system consists of removable orthodontic appliances (aligners), proprietary treatment planning 3D software, attachment templates and/or PFA system.

Like the predicate device, the Invisalign system with PFA (subject device) consists of a series of doctor prescribed, customized, thin, clear plastic aligners that gently move the patient's teeth in small increments from their original state to a more optimal, treated state to address dental malocclusion. The Invisalian system aligners are used in patients with primary, mixed (primary and permanent), and permanent dentition. The Invisalign system aligners with mandibular advancement feature(s) are used in patients with mixed and permanent dentition to correct Class II malocclusions. The Invisalign system is intended to treat dental and skeletal malocclusion in patients with Class I, II and III including Antero-Posterior (A-P), vertical (open bite, deep bite), transverse (narrow arch or jaw, crossbite), or inter-arch (spacing and crowding) correction at all severity levels. In some cases, surgical intervention, or addition of other appliances in addition to Invisalign treatment may be needed at the doctor's discretion.

The proprietary ClinCheck (CC) 3-D software is inclusive of both dental practitioner-facing functions and internal Align personnel-facing functions. The Align facing software enables Align's computer-aided design (CAD) designers to create a treatment plan based on a doctor's prescription and inputs (e.g., dental scans). The treatment plans created using the Align personnel-facing software are then reviewed and approved by doctors before the aligners are manufactured. The doctors' reviews and approvals are exchanged via ClinCheck software (dental practitioner-facing software). Once the treatment plan is approved by the dental practitioner, the information is sent to the manufacturing facility for creation of the aligners.

When attachments are prescribed as part of the treatment plan, the subject device has the option of delivering them preformed with PFA system or with a disposable attachment template. The attachment templates are disposable polyurethane appliances which match the patient's existing dentition and include wells for the placement of dental composite (sold separately). During the first visit, the dental practitioner uses the template in bonding dental composite to the tooth surface to create attachments on the teeth. These attachments help create forces on the tooth which can assist aligner retention or optimized aligner force system for tooth movement.

The PFAs are made of a fully cured proprietary photo-polymerizable methacrylate-based resin (similar to dental composite material). PFA system is intended to enable correct placement of attachments and bond attachments to the tooth surface for aligner retention and to optimize aligner force system for tooth movement.

The patient-customized PFA are manufactured using additive manufacturing technologies and configured to individual patient's treatment plans and teeth anatomy using a proprietary internal facing 3D device-generation manufacturing software.

AI/ML Overview

Based on the provided text, the device in question is the "Invisalign System with Pre-Formed Attachment System" (PFA System), which is an alternative attachment delivery mechanism for the existing Invisalign System. The 510(k) submission seeks clearance for this addition.

The provided text does NOT describe a typical AI/ML-based medical device performance study with acceptance criteria related to sensitivity, specificity, accuracy, or human reader improvement. Instead, it describes a modification to an existing medical device and demonstrates its substantial equivalence to a predicate device. The "performance data" section focuses on engineering and biocompatibility testing for the new component, not diagnostic performance metrics or human-AI interaction.

Therefore, many of the requested points related to AI/ML study design (such as sample size for test/training sets, expert ground truth establishment, MRMC studies, standalone performance, etc.) are not applicable to this specific submission, as it focuses on an engineering modification rather than an AI/ML diagnostic algorithm.

Here's a breakdown based on the information available:

1. Table of Acceptance Criteria and Reported Device Performance:

The document describes performance testing for the new PFA system, but it does not specify quantitative acceptance criteria in a table format with corresponding numerical performance results for each criterion. Instead, it makes a general statement that the testing outcomes support substantial equivalence.

Acceptance Criterion (Type of Test)	Reported Device Performance (Qualitative)
Functional and Performance Testing	"complete set of functional and performance testing" was done.
Bond Strength	Satisfactory. The PFA system "does not impact the current safety and effectiveness profile."
Stain Resistance	Satisfactory. The PFA system "does not impact the current safety and effectiveness profile."
Wear	Satisfactory. The PFA system "does not impact the current safety and effectiveness profile."
Force Measurement	Satisfactory. The PFA system "does not impact the current safety and effectiveness profile."
Volume Precision	Satisfactory. The PFA system "does not impact the current safety and effectiveness profile."
Usability Testing	Satisfactory. The PFA system "does not impact the current safety and effectiveness profile."
Biocompatibility (ISO 10993-1, ISO 7405)	"The results demonstrate that the PFA system does not pose any significant biologicals risks and is considered safe for its intended use in humans."
Software Verification & Validation (V&V) (IEC 62304)	"successful software verification and validation (V&V) testing at the unit, integration, and system level was performed to qualify the newly added software with the subject device."

2. Sample size used for the test set and the data provenance:

Sample Size: Not specified for the performance testing. The study is not a clinical trial or an AI/ML algorithm evaluation using patient data. It's an engineering and biocompatibility assessment of a new component.
Data Provenance: Not applicable in the context of patient data. The "data" refers to the results of engineering and lab tests (e.g., measuring bond strength, stain resistance).

3. Number of experts used to establish the ground truth for the test set and the qualifications of those experts:

Not Applicable. This is not an AI/ML diagnostic device where experts establish ground truth for images or clinical cases. The "ground truth" for this device modification is based on engineering specifications and regulatory standards (e.g., successful bond strength test, ISO biocompatibility compliance).

4. Adjudication method (e.g. 2+1, 3+1, none) for the test set:

Not Applicable. As there are no human readers establishing ground truth for diagnostic decisions, no adjudication method is described.

5. If a multi reader multi case (MRMC) comparative effectiveness study was done, If so, what was the effect size of how much human readers improve with AI vs without AI assistance:

No. An MRMC study was not done. This submission is about a mechanical/material modification (Pre-Formed Attachment system), not a diagnostic AI that assists human readers. No effect size on human reader improvement is relevant or reported.

6. If a standalone (i.e. algorithm only without human-in-the-loop performance) was done:

Not Applicable / Not a standalone AI algorithm. The new component is an alternative delivery mechanism for attachments in an orthodontic system that relies on a doctor's prescription and approval of treatment plans. It's not a standalone AI algorithm producing a diagnostic output. While there is "proprietary, 3D device-generation manufacturing software," its V&V is mentioned, but its performance is not assessed as a standalone diagnostic tool.

7. The type of ground truth used:

Engineering Specifications and Standardized Biocompatibility Testing Protocols. The ground truth for this kind of device modification is established by meeting predefined physical/mechanical properties and complying with established biocompatibility standards (e.g., ISO 10993-1, ISO 7405).

8. The sample size for the training set:

Not Applicable. This is not an AI/ML device that requires a "training set" of data in the sense of machine learning. The term "training set" usually refers to data used to train an algorithm. Performance assessment here relates to manufacturing processes and material properties.

9. How the ground truth for the training set was established:

Not Applicable. (See point 8).

In Summary:

The provided document describes a 510(k) submission for a non-AI device modification. The "study that proves the device meets the acceptance criteria" is a series of engineering, materials, and software verification and validation tests (bond strength, stain resistance, wear, force measurement, volume precision, usability, biocompatibility per ISO standards, and software V&V per IEC standards), rather than a clinical performance study evaluating an AI algorithm using patient data and expert ground truth. The acceptance criteria are implicitly met if the test outcomes validate that the new component "does not impact the current safety and effectiveness profile of the Invisalign System" and allows for a finding of "substantial equivalence" to the predicate device.

Summary

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December 22, 2022

Align Technology, Inc. John Ray Principal, Regulatory Affairs 2820 Orchard Parkway San Jose. California 95134

Re: K222894

Trade/Device Name: Invisalign System, Pre-Formed Attachment System Regulation Number: 21 CFR 872.5470 Regulation Name: Orthodontic Plastic Bracket Regulatory Class: Class II Product Code: NXC Dated: September 23, 2022 Received: September 23, 2022

Dear John Ray:

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.

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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.

Michael E. Adjodha -S

Michael E. Adjodha, M. ChE. Assistant Director DHT1B: Division of Dental and ENT Devices OHT1: Office of Ophthalmic, Anesthesia, Respiratory, ENT and Dental Devices Office of Product Evaluation and Quality Center for Devices and Radiological Health

Enclosure

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Indications for Use

510(k) Number (if known) K222894

Device Name

Invisalign System with Pre-Formed Attachment System

Indications for Use (Describe) The Invisalign System is intended for the orthodontic treatment of malocclusion.

Type of Use (Select one or both, as applicable)
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X Prescription Use (Part 21 CFR 801 Subpart D)

Over-The-Counter Use (21 CFR 801 Subpart C)

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Section 7: 510(K) Summary Align Technology's Invisalign System with Pre-Formed Attachment System

General Information

510(k) Sponsor	Align Technology, Inc.
Address	2820 Orchard ParkwaySan Jose, CA 95134
FDA Registration Number	2953749
Contact Person	Manjunath BisalehalliManager, Regulatory AffairsAlign Technology, Inc.cc: Shweta DagaDirector, Regulatory AffairsAlign Technology Inc.
Contact Information	Email: mbisalehalli@aligntech.comPhone: +1 408-789-1743Cell Phone: +1 412-298-4604Fax: +1408-470-1010
Date Prepared	September 23, 2022

Name of Modified Device and Name/Address of Sponsor

Name of Device	Invisalign System with Pre-Formed Attachment System
Name/Address of Sponsor	Align Technology, Inc.2820 Orchard Parkway, San Jose, CA 95134
Trade/Proprietary Name	Invisalign SystemPre-Formed Attachment System
Common Name	Aligner, Sequential
Classification Name	Orthodontic Plastic Bracket
Regulation Number	21 CFR 872.5470
Product Code	NXC
Regulatory Class	II

Predicate Device

Name of Device	Invisalign System
Name/Address of Sponsor	Align Technology, Inc.2820 Orchard Parkway, San Jose, CA 95134
Trade/Proprietary Name	Invisalign System
Common Name	Aligner, Sequential
Classification Name	Orthodontic Plastic Bracket
Regulation Number	21 CFR 872.5470
Product Code	NXC
Regulatory Class	II

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Purpose of the Traditional 510(k) notice

The purpose of this Traditional 510(k) notice is to request clearance for the addition of Pre-Formed Attachment (PFA) System to the Invisalign System's existing components. The PFA system is an optional alternative attachments bonding mechanism for Invisalign treatment.

Additionally, the Traditional 510(k) introduces the proprietary, 3D device-generation manufacturing software, labeling documentation associated with the PFA system, and the nonsignificant changes to the Invisalign System implementation since the last 510(k) clearance.

Intended Use

The Invisalign System with the Pre-Formed Attachment System (Modified device) has the same intended use as the cleared Predicate device, the Invisalign System (K220287), which is as follows:

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

Device Description

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(dental practitioner-facing software). Once the treatment plan is approved by the dental practitioner, the information is sent to the manufacturing facility for creation of the aligners.

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Comparison with Predicate Device

In accordance with 21 CFR 807.92(a)(6) a summary of the technological characteristics' comparison of the proposed modified device to the predicate Device is provided below.

Technological Characteristics comparison with the Predicate Device

The Invisalign System with Pre-Formed Attachment (PFA) System (subject device) introduces an alternative attachment delivery mechanism to Invisalign treatment. The proposed change does not alter the aligners' technological characteristics and does not impact the current safety and effectiveness profile of the Invisalign System.

	Invisalign System with PFA SystemSubject/Modified Device	Invisalign System (K220287)Predicate/ Existing Device	ComparisonAssessment
Intended Use/Indication forUse	The Invisalign System isintended for the orthodontictreatment of malocclusion.	The Invisalign System isintended for the orthodontictreatment of malocclusion.	Same as predicate device
PatientPopulation	Children, Adolescents andAdults	Children, Adolescents andAdults	Same as predicate device
Use Location	Dental intraoral Devices	Dental intraoral Devices	Same as predicate device
OTC orPrescription(Rx) Device	Rx only	Rx only	Same as predicate device
	Technological Characteristics
Principle ofOperation	Aligners: Sequential alignersapply continuous gentle forceto the teeth and/or positionmandible forward.	Aligners: Sequential alignersapply continuous gentle forceto the teeth and positionmandible forward	Same as predicate device
	3D Software: Produces 3D-model file of the PVSimpression or the digital scan.Identifies the individual teeththat requires treatment (i.e.,repositioning). Creates atreatment plan (i.e., 3-Dmodels that represent thetreatment plan) which isreviewed by the treating dentalpractitioner using ClinCheck'sdoctor facing function to rejector request modifications to theset-up prior to approval.	3D Software: Produces 3D-model file of the PVSimpression or the digital scan.Identifies the individual teeththat requires treatment (i.e.,repositioning). Creates atreatment plan (i.e., 3-Dmodels that represent thetreatment plan) which isreviewed by the treating dentalpractitioner using ClinCheck'sdoctor facing function to rejector request modifications to theset-up prior to approval.	Same as predicate device
	Delivery Mechanism of Attachment
	1) Attachment Template -Bonds dental composite(material provided by doctor)to the tooth surface to createattachments used for alignerretention or optimized aligner	1) Attachment Template -Bonds dental composite(material provided by doctor)to the tooth surface to createattachments used for alignerretention or optimized aligner	Same as predicate device
	Invisalign System with PFASystemSubject/Modified Device	Invisalign System (K220287)Predicate/ Existing Device	ComparisonAssessment
	force system for toothmovement.Delivery Mechanism: formedby dental practitioner who fillsand packs wells in theTemplate tray withcommercially available dentalcomposite. The final shape &configuration is cured when	force system for toothmovement.Delivery Mechanism: formedby dental practitioner who fillsand packs wells in theTemplate tray withcommercially available dentalcomposite. The final shape &configuration is cured when
	tray is seated on dentition.2) PFA System –enables correct placement ofattachments and bondattachments to the toothsurface for aligner retentionand to optimize aligner forcefor tooth movement.Delivery of Mechanism: theattachment shape andconfiguration defined by thetreatment plan, manufacturedtogether with positioner. Theshapes are cured to the toothwhen the positioner is seatedon dentition	tray is seated on dentition.2) Not applicable	Similar to predicatedeviceThe attachmentconfiguration prescribedby treatment is identical tothe predicate device,however the mechanismof delivery attachmentsonto the dentition isdifferent. Therefore, thesubject device issubstantially equivalent tothe predicate device
Material	Aligners and AttachmentTemplates - Thermoplasticpolymer	Aligners and AttachmentTemplates - Thermoplasticpolymer	Same as predicate device
	PFA System - Photo-polymerizable methacrylate-based resin	Not applicable	Similar to predicatedeviceAlthough the material isdifferent when thealternative attachmentdelivery mechanism, pre-formed attachments, isprescribed by the Doctor.The pre-formedattachments material isbiocompatible and hasdemonstrated that it candeliver the force systemwith the Invisalign System.
Lower JawAdjustmentMechanism	Invisalign System aligners withmandibular advancementfeature (MAF) such asenhanced precision wings witha curved design. For Invisalignsystem with standard alignersthis is not applicable.	Invisalign System aligners withmandibular advancementfeature (MAF) such asenhanced precision wings witha curved design. For Invisalignsystem with standard alignersthis is not applicable.	Same as predicate device

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Performance Data

The existing Invisalign System's components: aligners, 3D software and attachment template, remain unchanged from the predicate device. The newly added PFA system as an optional alternative attachment delivery mechanism, underwent a complete set of functional and performance testing; including, but not limited to bond strength, stain resistance, wear, force measurement, volume precision, and usability testing. Based on the performance testing outcomes, the proposed addition of PFA system does not impact the current safety and effectiveness profile of the Invisalign System and is substantially equivalent to the predicate device.

No animal or clinical testing was required to validate these modifications implemented to the Invisalign System.

Biocompatibility

The existing Invisalign System's components: aligners, 3D software and attachment template, remain unchanged from the predicate device. Biocompatibility testing was completed for the proposed PFA system and assessed in accordance with ISO 10993-1, Biological evaluation of medical devices - Part 1: Evaluation and testing within a risk management process, and ISO 7405, Dentistry - Evaluation of biocompatibility of medical devices used in dentistry. The results demonstrate that the PFA system does not pose any significant biologicals risks and is considered safe for its intended use in humans.

Software Testing

In accordance with IEC 62304. Medical device software - Software life cycle processes; successful software verification and validation (V&V) testing at the unit, integration, and system level was performed to qualify the newly added software with the subject device.

Substantial Equivalence

The subject device is a modification to the predicate device, Invisalign System (K220287), which was cleared on April 7th, 2022. The subject device and the previously cleared predicate device are similar in that they have:

same intended use,
same indications for use,
. similar principles of operation, and
similar technological characteristics

The minor differences in the principles of operation and technological characteristics between the subject device and predicate device do not raise different questions of safety or efficacy. Therefore, the subject device is found to be substantially equivalent to the legally marketed predicate device, Invisalign System (K220287).

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Conclusion

Align Technology's Invisalign system with the PFA system has the same intended use and indications for use as the previously cleared Invisalign system (K220287). The minor principles of operation and technological differences between the subject device and its predicate device do not raise new issues of safety or effectiveness. Performance data and biocompatibility testing demonstrate that the subject device is as safe and effective as the predicate Invisalign System. Thus, the modified Invisalign system with PFA system is substantially equivalent to the 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.