Motiva SmoothSilk Round Ergonomix Silicone Gel-Filled Breast Implants, Motiva SmoothSilk Round Silicone Gel-Filled Breas

P230005 · Motiva USA, LLC · FTR · Sep 26, 2024 · General, Plastic Surgery

Device Facts

• Record ID: P230005
• Device Name: Motiva SmoothSilk Round Ergonomix Silicone Gel-Filled Breast Implants, Motiva SmoothSilk Round Silicone Gel-Filled Breas
• Applicant: Motiva USA, LLC
• Product Code: FTR · General, Plastic Surgery
• Decision Date: Sep 26, 2024
• Decision: APPR
• Regulation: 21 CFR 878.3540
• Device Class: Class 3
• Attributes: Therapeutic

Indications for Use

The Motiva SmoothSilk Round and SmoothSilk Round Ergonomix breast implants are indicated for breast augmentation for women of at least 22 years old. Breast augmentation includes primary breast augmentation to increase the breast size, as well as revision surgery to correct or improve the result of an original primary breast augmentation surgery (i.e., revision-augmentation).

Device Story

Silicone gel-filled breast implants used for breast augmentation; single-lumen silicone elastomer shell with SmoothSilk surface architecture; optional passive RFID microtransponder for unique serial number identification. Implants are surgically placed by plastic surgeons in clinical settings. RFID microtransponder is 9mm wide and 2mm high, embedded in the gel. During MRI, RFID may cause susceptibility artifacts; managed via standard MR techniques or dual-modality imaging (e.g., ultrasound). Implants provide aesthetic breast volume increase. Clinical decision-making supported by patient satisfaction and quality-of-life assessments.

Clinical Evidence

Prospective, multicenter, 10-year open-label study (560 subjects, 1,119 implants). Primary endpoints: safety (adverse event rates) and effectiveness (patient/physician satisfaction, BREAST-Q, QOL scales). 3-year results: Any complication rate 8.4% (primary) and 28.4% (revision). Reoperation rates 6.1% (primary) and 25.8% (revision). MRI sub-study (n=218) evaluated rupture; 3-year rupture risk 0.6% (primary) and 0.0% (revision). Effectiveness: 97.1% primary and 87.5% revision subjects satisfied at 3 years.

Technological Characteristics

Single-lumen silicone elastomer shell (Nusil MED-6400/6600) with SmoothSilk surface (4-micron roughness). Filler: platinum-cured silicone gel (MED3-6311). Optional passive RFID microtransponder (copper wire, nickel-zinc ferrite core, ASIC). Sterilization: dry heat. Shelf life: 5 years. ASTM F703-18 compliance for mechanical properties.

Indications for Use

Indicated for breast augmentation in women aged 22 and older, including primary augmentation and revision-augmentation. Contraindicated in women with active infections, untreated cancer or precancerous conditions, or who are pregnant or nursing.

Regulatory Classification

Identification

(1) Single-lumen silicone gel-filled breast prosthesis. A single-lumen silicone gel-filled breast prosthesis is a silicone rubber shell made of polysiloxane(s), such as polydimethylsiloxane and polydiphenylsiloxane. The shell either contains a fixed amount cross-linked polymerized silicone gel, filler, and stabilizers or is filled to the desired size with injectable silicone gel at time of implantation. The device is intended to be implanted to augment or reconstruct the female breast.(2) Double-lumen silicone gel-filled breast prosthesis. A double lumen silicone gel-filled breast prosthesis is a silicone rubber inner shell and a silicone rubber outer shell, both shells made of polysiloxane(s), such as polydimethylsiloxane and polydiphenylsiloxane. The inner shell contains fixed amounts of cross-linked polymerized silicone gel, fillers, and stabilizers. The outer shell is inflated to the desired size with sterile isotonic saline before or after implantation. The device is intended to be implanted to augment or reconstruct the female breast.(3) Polyurethane covered silicone gel-filled breast prosthesis. A polyurethane covered silicone gel-filled breast prosthesis is an inner silicone rubber shell made of polysiloxane(s), such as polydimethylsiloxane and polydiphenylsiloxane, with an outer silicone adhesive layer and an outer covering of polyurethane; contained within the inner shell is a fixed amount of cross-linked polymerized silicone gel, fillers, and stabilizers and an inert support structure compartmentalizing the silicone gel. The device is intended to be implanted to augment or reconstruct the female breast.

Submission Summary (Full Text)

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SUMMARY OF SAFETY AND EFFECTIVENESS DATA (SSED)

I. GENERAL INFORMATION

Device Generic Name: Prosthesis, Breast, Noninflatable, Internal, Silicone Gel-Filled

Device Trade Name: Motiva SmoothSilk Round Silicone Gel-Filled Breast Implants

Motiva SmoothSilk Round Ergonomix Silicone Gel-Filled Breast Implants

Device Product Code: FTR

Applicant’s Name and Address: Motiva USA LLC
125 East De La Guerra Street Suite 203A
Santa Barbara, CA 93101

Date(s) of Panel Recommendation: None

Premarket Approval Application (PMA) Number: P230005

Date of FDA Notice of Approval: September 26, 2024

II. INDICATIONS FOR USE

The Motiva SmoothSilk Round and SmoothSilk Round Ergonomix breast implants are indicated for breast augmentation for women of at least 22 years old. Breast augmentation includes primary breast augmentation to increase the breast size, as well as revision surgery to correct or improve the result of an original primary breast augmentation surgery (i.e., revision-augmentation).

III. CONTRAINDICATIONS

Breast implant surgery is contraindicated in women
- With active infections anywhere in their body,
- With existing cancer or precancerous conditions who have not received adequate treatment for those conditions, or
- Who are currently pregnant or nursing.

IV. WARNINGS AND PRECAUTIONS

The warnings and precautions can be found in the Motiva Implants labeling.

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# V. DEVICE DESCRIPTION

A description of 1) Motiva SmoothSilk Round Silicone Gel-Filled Breast Implants (also referred to as "Motiva Implants Round ProgressiveGel Plus" or "Round") and 2) Motiva SmoothSilk Round Ergonomix Silicone Gel-Filled Breast Implants (also referred to as "Motiva Implants Ergonomix Round ProgressiveGel Ultima" or "Round Ergonomix") is provided below.

Motiva Round and Round Ergonomix silicone breast implants are comprised of a single-lumen silicone elastomer shell and a filler made of silicone gel. The shell is constructed of successive cross-linked layers of silicone elastomer (standard dispersion) and a low diffusion barrier layer (barrier dispersion) containing blue pigment, which together provide the mechanical characteristics and integrity of the device. The material components of the Shell and the Gel of the Round and Round Ergonomix devices are identical although there are differences in the construction of each device type; the Round Ergonomix implant contains one less layer of standard dispersion and a gel that is slightly less firm than the Round implant.

The Shell of both style implants has a SmoothSilk controlled surface architecture produced by the mandrel imprinting technique with an average roughness of 4 microns.

A passive radio frequency identification device (referred to as RFID, microtransponder, or Qid) that is placed in the Gel at the Shell/Patch area is an optional feature for all implant styles. This microtransponder provides each implant with a unique electronic serial number. The implants are sterilized by dry heat and have a 5-year shelf life from the date of sterilization.

Table 1 includes the styles/catalogs that are approved for commercial use by FDA and Table 2 lists the formulation of the Shell, Patch, and Gel components.

Table 1: The Motiva Implant Matrix

| Motiva Implant Matrix | | | |
| --- | --- | --- | --- |
| Style | Volume | Base Width | Projection |
| Round | | | |
| Mini | 245cc - 400cc | 11.5cm - 13.5cm | 2.8cm - 3.2cm |
| Demi | 205cc - 525cc | 10.0cm - 14.0cm | 3.5cm - 4.5cm |
| Full | 255cc - 625cc | 10.25cm - 14.0cm | 4.2cm - 5.7cm |
| Round Ergonomix | | | |
| Mini | 150cc - 475cc | 9.75cm - 14.5cm | 2.4cm - 3.4cm |
| Demi | 155cc - 575cc | 9.0cm - 14.5cm | 3.3cm - 4.6cm |
| Full | 255cc - 625cc | 10.25cm - 14.0cm | 4.2cm - 5.7cm |
| | | | |
| Differences Between Round and Round Ergonomix | | | |
| Parameter | Round | | Round Ergonomix |

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Table 2: Materials of Motiva Implants

| Component | Material | |
| --- | --- | --- |
| Shell: Standard layers | Nusil Technology dimethyl-diphenyl silicone elastomer dispersion (MED-6400) | |
| Shell: Barrier layer | Nusil Technology dimethyl-diphenyl silicone elastomer dispersion (MED-6600) | |
| Barrier Layer Indicator | NuSil Technology biocompatible blue pigment dispersed in vinyl functional silicone polymer (MED 4800-7) | |
| Patch Assembly | NuSil Tech barrier silicone elastomer double layer plus high-consistency, vinyl-functional, non-catalyzed elastomeric adhesive MED7-6600 (or MED-6600), MED-2174, and MED1511 RTV-cure silicone adhesive. | |
| Filling Gel-ProgressiveGel PLUS | NuSil Technology platinum-cured siloxane gel (MED3-6311) | |
| Filling Gel-ProgressiveGel Ultima | NuSil Technology platinum-cured siloxane polymer (MED3-6311) | |
| *Passive radio frequency identification (RFID) microtransponder | Copper polystermide estersol 180 wire, nickel-zinc ferrite core, Photobond 4442 acrylate adhesive, 4305 Application Specific Integrated Circuit (ASIC), and soda-lime silicate glass | |

*optional

VI. ALTERNATIVE PRACTICES AND PROCEDURES

There are several other alternatives for the augmentation of the breast with silicone gel-filled breast implants. Alternative procedures include saline-filled breast implant surgery, external prostheses, autologous tissue grafts, or no treatment. Each alternative has its advantages and disadvantages. A patient should fully discuss these alternatives with their physician to select the method that best meets expectations and lifestyle.

VII. MARKETING HISTORY

Motiva Implants devices have been marketed outside the United States since October 2010. In 2011, Motiva Implants were CE Marked for commercialization in European markets.

In 2014, the Motiva Implants device family added the Round Ergonomix devices, introducing ProgressiveGel Ultima and the addition of the RFID microtransponder. Motiva Implants devices have never been withdrawn from the market for any reason related to their safety or effectiveness.

In 2018, Motiva USA, a wholly owned subsidiary of Establishment Labs, LLC., received

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FDA IDE approval to begin its Core Clinical Study for Silicone Gel-Filled Breast Implants. The Core Study is the primary source of data for this PMA.

## VIII. POTENTIAL ADVERSE EFFECTS OF THE DEVICE ON HEALTH:

Below is a list of the potential adverse events (e.g., complications) associated with the use of the device.

- Animation deformity
- Asymmetry
- Breastfeeding difficulties
- Breast Implant-Associated Anaplastic Large Cell Lymphoma (BIA-ALCL)
- Breast pain
- Breast tissue atrophy
- Cancer, including breast
- Calcifications/Calcium deposits
- Capsular contracture
- Chest wall deformity
- Connective Tissue Disease (CTD)
- CTD signs and symptoms
- Double capsule
- Delayed wound healing
- Hematoma
- Iatrogenic injury/Damage
- Implant extrusion
- Implant malposition/displacement
- Implant palpability/visibility
- Implant removal with/without replacement
- Implant rupture
- Infection including Toxic Shock Syndrome
- Inflammation/Irritation
- Lymphedema
- Lymphadenopathy
- Mass/Cyst/Lump
- Necrosis
- Neurological disease
- Neurological signs and symptoms
- Nipple/Breast sensation changes
- Nipple complications
- Potential effects on offspring
- Ptosis
- Redness/Bruising
- Reoperation
- Reproductive problems

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- Scarring, including hypertrophic/abnormal
- Seroma
- Skin rash
- Suicide
- Systemic symptoms (Breast implant illness)
- Unsatisfactory style/size
- Wrinkling/Rippling

There have been reports of Squamous Cell Carcinoma (SCC) and various lymphomas in the capsule around breast implants. However, the cause, incidence, and risk factors remain unknown.

Refer to Section X for a summary of the adverse events in the Motiva Implants Core Clinical Study.

## IX. SUMMARY OF PRECLINICAL STUDIES

The following preclinical studies are included in this section: chemistry data, toxicology data, mechanical data, modes and causes of rupture, and shelf life.

## A. Chemistry Data

### 1. Extent of Cross-linking

**Shell**

The extent of cross-linking was measured for the Shell based on mechanical testing consisting of break force and elongation. The minimum break force and elongation percentage were 3.2 lbs and 522%, respectively. This testing demonstrated that the extent of cross-linking of the elastomers is sufficient to ensure that the Shell meets the ASTM F703-18 [1] specification of a minimum break force of 2.5 lb and a minimum elongation of 350%.

**Gel**

Penetrometer testing was conducted on every lot of Gel to ensure that the cross-link density conforms to predetermined specifications. The uniformity of the cross-linking density across all lots of gel used in the implants is confirmed by testing each Gel lot used for implant manufacture. All lots of Gel used in the implants have an extent of cross-linking sufficient to conform with the internal specification.

### 2. Volatiles

The Shell was tested for volatiles using Gas Chromatography/Mass Spectrometry (GC/MS). Isopropyl alcohol, Trimethyl silanol, Xylene (m or p), 2,2-dimethylpropanoic acid, 2-ethyl-1-hexanol, D5, and D6 were detected in the Round Ergonomix shells. Trimethyl silanol, Xylene (m or p), 2,2-dimethylpropanoic acid, D5, D6, and D8 were detected in the Round shells. All volatile compounds were at concentrations below 1 µg/g

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test article; a toxicological risk assessment determined that the concentrations of all volatile compounds were below the threshold of toxicological concern.

No other volatile compounds were detected.

## 3. Extractables

Components of the device were extracted with different solvents exhaustively. The extracts were analyzed as described below.

**Gravimetric Analysis**: For the Shell/Patch, the duration of the exhaustive extraction for purified water (PW) was 96 hours (4 days). The average non-volatile residue (NVR) reduced from 1.0 to 0.0 mg/unit in 4 days. The duration of the exhaustive extraction for dichloromethane (DCM) was 120 hours (5 days). The average NVR reduced from 603.4 to 23.9 mg/unit in 5 days. The exhaustive extraction for hexane was 120 hours (5 days). The average NVR reduced from 653.5 to 40.7 mg/unit in 5 days. All extractions met the exhaustive extraction requirement, i.e., the amount of NVR was not detectable or less than 10% of the original value.

For the Gel/Microtransponder, the duration of the exhaustive extraction for PW was 120 hours (5 days). The average NVR reduced from 1.9 to 0.0 mg/unit in 5 days. The duration of the exhaustive extraction for dimethylsulfoxide (DMSO) was 144 hours (6 days). The average NVR reduced from 23.6 to 1.1 mg/unit in 6 days. The PW and DMSO extractions met the exhaustive extraction requirement, i.e., the amount of NVR was not detectable or less than 10% of the original value. The exhaustive extraction for ethanol plateaued at 216 hours (9 days).

The extraction was continued for an additional 3 days for a total of 288 hours (12 days). The average NVR reduced from 692.5 to 231.1 mg/unit in 12 days. It did not reach the exhaustive time point in 12 days.

**FTIR (Fourier Transform Infra-Red) Analysis**: The FTIR spectra of the DCM and hexane extracts of the Shell/Patch were similar. Many absorption bands matched those in the FTIR spectra of dimethyl silicone. The FTIR spectra of the PW extract were consistent with the observation of chlorinated aromatic compounds in the semivolatile organic compounds (SVOC) analysis.

Many of the absorption bands of the Ethanol (EtOH) and DMSO extracts of the Gel/Microtransponder matched those in the FTIR spectra of dimethyl silicone. The FTIR spectra of the PW extract were consistent with the observation of chlorinated aromatic compounds in the SVOC analysis.

**Gel Permeation Chromatography (GPC)**: Four extracts each of the Shell/Patch and Gel/Microtransponder and four control samples were submitted for analysis. The extracts were DCM, hexane, EtOH, and DMSO. Sample extracts were diluted in toluene (DCM, hexane, and EtOH) or liquid-liquid extracted with toluene (DMSO) to prepare them for

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GPC analysis. The system was calibrated using polystyrene standards.

The lowest average molecular weight was observed in the EtOH extract of the Gel/Microtransponder and was approximately $4.0\mathrm{kDa}$ relative to polystyrene standards. The highest average molecular weight was observed in the hexane extract of the Shell/Patch and was approximately $15.2\mathrm{kDa}$ relative to polystyrene standards. The average weight fraction below $1000\mathrm{Da}$ was $3.77\%$ for the DCM extract of the Shell/Patch, $4.11\%$ for the hexane extract of the Shell/Patch, and $0.75\%$ for the EtOH extract of the Gel/Microtransponder. No polymeric material was detected in the DMSO extract of the Gel/Microtransponder.

Qualitative and Quantitative Analyses of Extractables: The residue from the Shell/Patch and Gel/Microtransponder extractions was subjected to GC/MS. The results are listed in Table 3 below. All Margin of Safety (MOS) for D3 to D10 compounds were $>1.0$ . However, the MOS for the combined cyclic polydimethylsiloxane oligomers $(\mathrm{D_x - D_x})$ was $< 1.0$ . The concentrations of this compound family for the Shell/Patch and the Gel/Microtransponder overestimate exposure, and subsequent MOS, since the values represent the combined concentration for all cyclic compounds and not the concentrations of a single compound. The risk posed by the cyclic polydimethylsiloxane oligomers are mitigated by endpoint-specific testing per ISO 10993-1. Please see the Toxicology section below for more information.

Table 3: Semi-volatiles Analysis by GC/MS

| | Motiva SmoothSilk Round ErgonomixBreast Implants | | | Motiva SmoothSilk Round Breast Implants | | |
| --- | --- | --- | --- | --- | --- | --- |
| Cyclic Siloxane | Total Concentration (μg/g) | Shell and Patch (μg/g) | Gel and Qid (μg/g) | Total Concentration (μg/g) | Shell and Patch (μg/g) | Gel and Qid (μg/g) |
| D3 | ND | ND | ND | ND | ND | ND |
| D4 | 0.37 | ND | 0.37 | 0.32 | ND | 0.32 |
| D5 | 0.96 | 0.74 | 0.22 | 1.11 | 0.61 | 0.50 |
| D6 | 2.65 | 1.57 | 1.08 | 4.30 | 0.98 | 3.32 |
| D7 | 2.19 | 1.37 | 0.82 | 9.39 | 7.15 | 2.24 |
| D8 | 3.96 | 3.73 | 0.22 | 43.86 | 43.48 | 0.39 |
| D9 | 15.76 | 15.46 | 0.30 | 17.56 | 17.33 | 0.23 |
| D10 | 44.84 | 44.13 | 0.71 | 48.44 | 48.02 | 0.41 |
| D11 | 100.30 | 99.07 | 1.23 | 100.10 | 99.30 | 0.81 |
| D12 | 1037.19 | 1035.29 | 1.90 | 144.47 | 142.88 | 1.59 |
| D13 | 235.71 | 232.40 | 3.31 | 202.03 | 198.38 | 3.65 |
| D14 | 275.50 | 269.55 | 5.94 | 247.29 | 237.74 | 9.55 |
| D15 | 305.85 | 296.55 | 9.30 | 269.40 | 255.98 | 13.42 |
| D16 | 326.56 | 312.29 | 14.27 | 287.59 | 267.14 | 20.45 |
| D17 | 355.74 | 335.38 | 20.36 | 287.63 | 259.29 | 28.34 |

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| | Motiva SmoothSilk Round ErgonomixBreast Implants | | | Motiva SmoothSilk Round Breast Implants | | |
| --- | --- | --- | --- | --- | --- | --- |
| Cyclic Siloxane | Total Concentration (μg/g) | Shell and Patch (μg/g) | Gel and Qid (μg/g) | Total Concentration (μg/g) | Shell and Patch (μg/g) | Gel and Qid (μg/g) |
| D18 | 1145.67 | 1102.79 | 42.88 | 806.93 | 770.38 | 36.54 |
| D19 | 630.42 | 590.78 | 39.64 | 494.92 | 447.32 | 47.60 |
| D20 | 1311.49 | 1277.19 | 34.30 | 192.12 | 147.59 | 44.53 |
| Total cyclic siloxanes | 5795 | 5618 | 177 | 3157 | 2944 | 214 |

ND, not detected

## 4. Heavy Metals

Samples of the shell/patch and gel/microtransponder materials were digested in acid and the metals were analyzed by Inductively Coupled Plasma/Mass Spectrometry (ICP/MS). The metals analysis is presented below in Table 4.

Table 4: Quantification of Heavy Metals by ICP/MS*

| | Motiva SmoothSilk Round Ergonomix Breast Implants | | Motiva SmoothSilk Round Breast Implants | |
| --- | --- | --- | --- | --- |
| Element | Shell Concentration (μg/g) | Gel Concentration (μg/g) | Shell Concentration (μg/g) | Gel Concentration (μg/g) |
| Beryllium | <0.5 | <0.5 | <0.5 | <0.5 |
| Magnesium | <0.5 | <0.5 | <0.5 | <0.5 |
| Titanium | <0.5 | <0.5 | <0.5 | <0.5 |
| Vanadium | <0.5 | <0.5 | <0.5 | <0.5 |
| Chromium | <0.5 | <0.5 | 0.9 | <0.5 |
| Cobalt | <0.5 | <0.5 | <0.5 | <0.5 |
| Nickel | <0.5 | <0.5 | 0.6 | <0.5 |
| Copper | 1.1 | <0.5 | 0.8 | <0.5 |
| Zinc | <0.5 | <0.5 | <0.5 | <0.5 |
| Arsenic | <0.5 | <0.5 | <0.5 | <0.5 |
| Selenium | <0.5 | <0.5 | <0.5 | <0.5 |
| Molybdenum | <0.5 | <0.5 | <0.5 | <0.5 |
| Silver | <0.5 | <0.5 | <0.5 | <0.5 |
| Cadmium | <0.5 | <0.5 | <0.5 | <0.5 |
| Tin | <0.5 | <0.5 | <0.5 | <0.5 |
| Antimony | <0.5 | <0.5 | <0.5 | <0.5 |
| Barium | <0.5 | <0.5 | <0.5 | <0.5 |
| Platinum | 4.6 | 3.0 | 4.3 | 3.0 |

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| Mercury | <0.5 | <0.5 | <0.5 | <0.5 |
| --- | --- | --- | --- | --- |
| Lead | <0.5 | <0.5 | <0.5 | <0.5 |

*Limit of detection for all compounds $= {0.5\mu }\mathrm{g}/\mathrm{g}$

A small amount of platinum, the catalyst for the curing mechanism, was detected. Platinum is a metal used as a catalyst in the manufacture of the Shell and Gel Materials of silicone breast implants. The small amount of platinum remaining in the product may enter the body, either by diffusing through the intact Shell (i.e., through gel bleed) or through an implant rupture. Based on the existing literature, FDA has concluded that the platinum contained in breast implants is in the zero-oxidation state, which has the lowest toxicity, and thus, does not pose a significant risk to women with silicone breast implants.

FDA has posted a Backgrounder on its website that provides a brief summary of the key scientific studies on platinum and silicone gel-filled breast implants: http://www.fda.gov/medical-devices/breast-implants/fda-backgrounder-platinum-silicone-breast-implants.

# 5. Silica Filler

X-ray diffraction studies of the elastomer shell confirmed that the silica used as reinforcing material is in amorphous form.

# B. Toxicology Data

Motiva provided biocompatibility testing to address the biological safety of the material used in the implants.

# Pharmacokinetics

The pharmacokinetics of the implants has been addressed through a risk assessment based on exhaustive solvent extraction data from different extraction studies conducted on the implants and empirical biological testing. A scientific evaluation of the potential for the extractable/leachable chemicals from the Round and Round Ergonomix breast implants to accumulate in the body at concentrations that cause human health risks was determined as de minimus using a risk-based and weight-of-evidence approach. Based on this analysis, additional pharmacokinetic testing was not warranted since the empirical biological testing, which included long-term chronic toxicity and carcinogenicity, has demonstrated no adverse effects with clinically exaggerated doses.

# Biocompatibility Testing

The biocompatibility testing shown below in Table 5 was conducted on the Shell/Patch and Gel/Microtransponder components following ISO 10993-1:2018 [2]; FDA Guidance 'Saline, Silicone Gel, and Alternative Breast Implants. Guidance for Industry and Food and Drug Administration Staff' (2020); and FDA Guidance 'Use of International Standard ISO 10993-1, Biological evaluation of medical devices - Part 1: Evaluation and testing within a risk management process-Guidance for Industry and Food and Drug Administration Staff' (2020).

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The preclinical studies results demonstrate the biocompatibility of the materials in the Motiva silicone gel-filled implants. The testing conducted is summarized in Table 5 below:

Table 5: Summary of Biocompatibility Results

| Test | Purpose | Acceptance Criteria | Results |
| --- | --- | --- | --- |
| Cytotoxicity | Extracts of the shell/patch and gel/microtransponder were evaluated for cytotoxicity in cultured L-929 mouse fibroblasts. | No evidence of cell lysis or toxicity (reactivity less than grade 2) | No evidence of cytotoxicity |
| Sensitization | The shell/patch and gel/microtransponder were extracted in sodium chloride or sesame oil to assess skin sensitization in the guinea pig maximization test. | No evidence of delayed dermal reaction (dermal reaction less than grade 1) | No evidence of delayed dermal reaction |
| Irritation | The shell/patch and gel/microtransponder were extracted in sodium chloride or sesame oil to examine for irritation in the intracutaneous reactivity test in rabbits. | Mean erythema/ edema difference score of test article vs. control of less than 1.0 in either vehicle | No evidence of irritation |
| Acute Systemic Toxicity | The shell/patch and gel/microtransponder were extracted in sodium chloride or sesame oil to evaluate acute systemic toxicity in mice. | No mortality or evidence of toxicity | No mortality or evidence of toxicity |
| Material-mediated Pyrogenicity | Extracts of the shell/patch and gel/microtransponder were assessed for a pyrogenic response in rabbits. | No rise in temperature of 0.5 °C or greater from baseline | No induction of a pyrogenic response |
| Subchronic Toxicity | The shell/patch and gel/microtransponder were examined in a 4-week toxicity study in mice. | No evidence of systemic toxicity | No evidence of systemic toxicity |
| Genotoxicity | Extracts of the shell/patch and gel/microtransponder were assessed for mutagenicity in the bacterial reverse mutation assay with and without metabolic activation. | < 2-fold increase in the number of revertants vs. control for TA98, TA100, and WP2uvrA; < 3-fold increase in the number of revertants vs. control for TA1535 and TA1537 | No evidence of mutagenicity |
| | Extracts of the shell/patch and gel/microtransponder were assessed for genotoxicity in Chinese hamster ovary cells with and without metabolic activation. | No statistically significant increase in chromosome aberrations vs. control | No evidence of mutagenicity |

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| Test | Purpose | Acceptance Criteria | Results |
| --- | --- | --- | --- |
| | Extracts of the shell/patch and gel/microtransponder were assessed *in vivo* for micronuclei formation in mice. | No biologically relevant increase in micronucleated reticulocytes vs. control | No induction of micronuclei formation |
| Hemo-compatibility | The intact device was tested for hemolytic activity in human plasma. | Hemolytic Index = 0-2 | Negative for hemolytic activity |
| | The intact device was tested for complement activation in human plasma. | No statistically significant increase in SC5b-9 concentrations vs. control | Negative for complement activation |
| Chronic Toxicity by Implantation | The shell/patch and gel/microtransponder were implanted SC* in rats for 26 weeks to assess chronic toxicity and local effects. | No evidence of systemic toxicity or local irritation | No evidence of chronic systemic toxicity or local irritation |
| Carcinogenicity | The shell/patch and gel/microtransponder were implanted SC in transgenic rasH2 mice for 26 weeks to assess carcinogenicity. | No increase in tumor incidence vs. control | No evidence of carcinogenicity |
| Reproductive/Developmental Toxicity | The shell/patch and gel/microtransponder were implanted SC in rats from the premating to weaning period to assess reproductive toxicity. | No evidence of F0 or F1 systemic toxicity, F0 or F1 reproductive toxicity, or F1 neuro-behavioral toxicity | No evidence of reproductive or developmental toxicity |
| | The shell/patch and gel/microtransponder were implanted SC in rats from gestational days 6-21 to assess embryo/fetal developmental toxicity. | No evidence of F0 systemic toxicity or F1 developmental toxicity | |
| Immunotoxicity | The shell/patch and gel/microtransponder were implanted SC in rats for 4 weeks to assess immunotoxicity. | No effect on total T cells, helper T lymphocytes, cytotoxic T lymphocytes, B lymphocytes, NK cells, or NK-T cells in peripheral blood or spleen | No evidence of immunotoxicity |

*SC, subcutaneously

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## C. Mechanical Data

### 1. Fatigue Testing

Cyclic fatigue testing was conducted according to FDA Guidance, Saline, Silicone Gel, and Alternative Breast Implants, Guidance for Industry and Food and Drug Administration Staff, September, 2020. The testing was conducted in air at ambient temperature. Samples were tested at 3 Hz at various load levels to either run out (6.5 million cycles) or failure; the load where no failure was observed is the endurance load. Dry heat sterilized, RFID-containing, finished devices covering the “four corners” (105 cc Mini, 180 cc Corsé, 525 cc Mini, 1050 cc Corsé) were assessed. Please note that Corsé is a projection style that has a higher projection than the Full style and is not included as part of the approved styles. Additionally, this test assesses implant sizes smaller than approved in this PMA. The lowest observed endurance load after 6.5 million cycles at 3 Hz was 56 lbs for the 180 cc Corsé size for both Round and Round Ergonomix Implants. This endurance load is significantly higher than the loads experienced during walking, jogging, running, and lying face down.

### 2. Gel Bleed Testing

Intact implants were extracted in bovine serum albumin to model the natural condition of the breast implant. The test methods described in FDA Guidance, Saline, Silicone Gel, and Alternative Breast Implants, Guidance for Industry and Food and Drug Administration Staff, September, 2020, ASTM F703-18 [1], and ISO 14607:2018 were used to measure the gel bleed of Round and Round Ergonomix implants by measuring concentration of low molecular weight siloxanes and platinum at 1 hour, and every 10 days out to 70 days. At each time point, no cyclic/linear siloxanes were detected above the detection limit (LOD) of 0.6 µg/test article for Round and 0.9 – 2.0 µg/test article for Round Ergonomix; similarly, the platinum concentration measured in the serum extract was below the limit of detection of 0.0001 µg/test article for both implants.

### 3. Gel Cohesion Testing

Gel cohesivity and penetration testing were conducted on the ProgressiveGel Plus and Ultima silicone gels. The cone/pendant method was performed according to ASTM F703-18 [1]. All samples met the specifications in the standard. The data indicate that the gel provides form stability to retain breast implant shape.

## D. Modes and Causes of Rupture

Motiva provided multiple test reports and other information to characterize modes and causes of failure for its devices for a range of implantation periods, such as failure analyses of retrieved devices (i.e., retrieval study), physical property testing, assessment of manufacturing processes and surgical techniques that may impact rupture, as well as a review of the explant literature.

The Motiva Retrieval Study evaluated the physical characteristics and mechanical properties of the explants retrieved from the clinical study and analyzed the modes and causes of failure for study implants with abnormalities in the gel or ruptured shells. In addition, Motiva analyzed the

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durability of the retrieved study implants through elongation and shell thickness testing, to understand any potential correlations between the rupture(s) and the implantation conditions, mechanical properties, and clinical use of the implants over time.

After careful laboratory testing and analysis of 30 retrieved study implants, one (1) was confirmed to have an iatrogenic ruptured shell detected at 7 months after implantation. The implantation occurred in February 2019, and the explantation was performed in September 2019. Upon microscopic analysis and comparison with a visual aid tool (SID-001085 Visual aid for cutting marks inspection) used to analyze ruptured devices, the opening in the shell was confirmed to be consistent with a mechanical striation that was likely caused by interaction with an instrument. This conclusion aligned with the report from the explanting surgeon “during the surgical procedure, the right implant was inadvertently ruptured during the fat grafting portion of the surgery.”

Previous explant analysis studies show that instrument damage during surgery, or a concomitant breast procedure is the most common cause of implant shell failure. Per Handel et. al. (2013), "a number of risk factors for rupture have been identified; the most common cause is surgical instrument damage." (Handel et al, 2013. Breast Implant Rupture: Causes, Incidence, Clinical Impact, and Management. Plast. Reconstr. Surg. 132:1128.)

Overall, evaluation and analysis of the implants retrieved from the clinical study showed that the shells are robust during implantation, and surgical instruments primarily cause shell damage. To date, no correlations have been identified between implant failure and surgical parameters, implant characteristics, or subject variables in the Motiva Study.

1. Gel Strength

Gel strength testing of ProgressiveGel Ultima (Round Ergonomix breast implant) and ProgressiveGel Plus (Round breast implant) was performed to document the force values required to create a gel fracture. The Round Ergonomix and Round implant were placed on a base and the test probe attached to a 100 lb. load cell. The probe was driven into the implant with sufficient force to split the gel around the tip. The tip then contacts the bottom of the implant until a specified maximum load is detected. The gel strength results from ProgressiveGel Plus and ProgressiveGel Ultima passed the acceptance criteria of 15.87 lb-f, with a minimum force fracture value of 19.8 lb-f and 16.7 lb-f, respectively.

2. Gel Fracture and Incision Size

A gel fracture study of Round Ergonomix and Round breast implants at three incision sizes was performed using silicone torsos. Dry heat sterilized, RFID-containing, finished devices covering the “four corners” (105 cc Mini, 180 cc Corsé, 525 cc Mini, 1050 cc Corsé) were inserted through 6.0, 4.0, or 2.5 cm incisions and subsequently inspected for fracture. Please note that Corsé is a projection style that has a higher projection than the Full style and is not included as part of the approved styles. Additionally, this test assesses implant sizes smaller than approved in this PMA. The largest implant of (1050 cc Corsé) of both styles was unable to be inserted through the smallest (2.5 cm) incision even with the aid of an insertion sleeve. All other implants were able to be

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inserted through all incision sizes. No gel fracture was observed in any scenario. The results indicate that both Round Ergonomix and Round breast implants with or without the microtransponder remain intact with no signs of gel fracture through a range of inframammary incision sizes (2.5, 4.0, and 6.0 cm) under the defined test conditions.

## E. MRI Use for Gel Fracture Detection With and Without Implant Rupture

A gel fracture study with Round Ergonomix with RFID and Round Breast Implants with RFID was performed to determine whether gel fracture affects the ability of a MR scan to detect an implant rupture. Implants with ruptures and fractures, and negative controls were each placed inside of a phantom that contained water solution mixed with a Copper Sulfate powder (concentration 2g/L). All the MRI procedures were performed under a 1.5T Static Magnetic Field. For the additional MRI parameters refer to Table 6 below.

Table 6: Additional Description of MRI Parameters

| Parameter | Axial T1
FL3D HR | Sagittal T2 | Axial T2 | Sagittal T2
STIR | Coronal T2 |
| --- | --- | --- | --- | --- | --- |
| Repetition Time | 13 ms | 4810 ms | 2160 ms | 2940 ms | 2160 ms |
| Echo Time | 6.6 ms | 102 ms | 73 ms | 59 ms | 73 ms |
| Bandwidth | 250 kHz | 175 kHz | 815 kHz | 305 kHz | 815 kHz |
| Slice Location | 20 | 20 | 20 | 20 | 20 |
| Field of View | 360 x 360 mm | 200 x 200 mm | 400 x 400 mm | 400 x 400 mm | 400 x 400 mm |
| Section Thickness | 3 mm | 3 mm | 3mm | 3 mm | 3 mm |
| Flip Angle | 12° | 150° | 150° | 170° | 150° |
| Matrix Size (P×F) | 360 x 360 | 320 x 320 | 384 x 384 | 346 x 384 | 384 x 384 |

For the MRI scans evaluation, two radiologists performed this analysis. Both radiologists were blinded for the image analysis. Each radiologist performed an independent assessment of each MRI scan to determine presence or absence of ruptures based on clinical expertise. The data indicate that MR imaging has the ability to detect ruptures of Round Ergonomix and Round Breast Implants, even if they have an internal gel fracture, with overall sensitivity of 94% and specificity of 89%.

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F. Shelf Life

A 5-year shelf life was established for the Round and Round Ergonomix implants. The devices underwent accelerated and real-time aging, environmental conditioning, and shipping simulation, followed by product performance testing and packaging testing. Product performance testing assessed gel cohesion, shell elongation, break force, tension set, shell/patch joint strength, ultimate elongation, and break force. Packaging testing included challenges for seal strength and integrity by way of dye penetration and visual inspection. All device and package testing met the acceptance criteria set in the protocols. Therefore, the data supported a 5-year shelf life for the Motiva Implants.

X. SUMMARY OF MOTIVA IMPLANTS CORE CLINICAL STUDY

Motiva USA performed a clinical study to establish a reasonable assurance of the safety and effectiveness of primary breast augmentation and revision augmentation with Motiva Silicone Gel Breast Implants in the US under IDE G170186. Data from the primary and revision augmentation cohorts were the basis for the PMA approval decision. A summary of the clinical study and study results are presented below.

A. Study Design

The study is designed as a 10-year open-label, prospective, multicenter clinical study. The study assessed the safety and effectiveness of 560 primary and revision augmentation subjects implanted with 1,119 Motiva Silicone Gel Implants with at least 3-years of follow-up. The augmentation cohorts are comprised of 451 primary augmentation subjects and 109 revision augmentation subjects. Of the 560 subjects in the primary augmentation cohort, 511 subjects were enrolled in study sites located in the United States and 49 subjects were enrolled in study sites outside the United States (OUS). All the revision augmentation subjects were enrolled at study sites in the United States. Within the cohorts, a total of 218 subjects were enrolled into the MRI-cohort subgroup and a total of 154 subjects were enrolled in the RFID subgroup. Subjects were treated between April 17, 2018 and August 26, 2019. The database for this PMA reflected data collected through October 27, 2022, database lock. There were 23 implanting investigational sites: 20 study sites located in the United States and 3 study OUS, one located in Germany and two located in Sweden.

1. Clinical Inclusion and Exclusion Criteria

Enrollment in the study was limited to subjects who met the following inclusion criteria:

- Genetic female
- Subject is seeking one of the following procedures:
- Primary Breast Augmentation: age 22 and over, indicated to increase breast size
- Breast Implant Revision Surgery (removal and replacement of breast implants): revision surgery to correct or improve the results of a previous breast augmentation
- Subject has adequate tissue available to cover implant(s)
- Willingness to follow all study requirements including agreeing to attend all required follow-up visits and signs the informed consent

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- Agrees to have device returned to the Sponsor, if explanted
- Willing to undergo Magnetic Resonance Imaging (MRI) evaluation if medically advised

Subjects were not permitted to enroll in the study if they met any of the following exclusion criteria:

- Has any breast disease considered to be pre-malignant in one or both breasts or is reporting mutations in BRCA1 or BRCA2 without a previous bilateral mastectomy or an untreated cancer of any type
- Has inadequate or unsuitable tissue (e.g., due to radiation damage, ulceration, compromised vascularity, history of compromised wound healing)
- Has an abscess or infection
- Is pregnant or nursing or has had a full-term pregnancy or lactated within 6 months of enrollment
- Is taking any drugs that would interfere with blood clotting, or that might result in elevated risk and/or significant postoperative complications
- Has any medical condition such as obesity (body mass index, BMI &gt;40), diabetes, autoimmune disease, chronic lung or severe cardiovascular disease that might result in unduly high surgical risk and/or significant postoperative complications
- Has any connective tissue/autoimmune disorder or rheumatoid disease, such as systemic lupus erythematosus, discoid lupus, scleroderma, or rheumatoid arthritis, among others
- Has any condition that impedes the use of MRI including implanted metal device, claustrophobia, or other conditions that would make MRI scan prohibited
- Has a history of psychological characteristics that are unrealistic or unreasonable given the risks involved with the surgical procedure
- Has been implanted with any non-FDA approved breast implant
- Has been implanted with any silicone implant other than breast implants
- HIV positive (based on medical history)
- Has been diagnosed with anaplastic large cell lymphoma (ALCL)
- Works for the Sponsor or any of their subsidiaries, the study surgeon, or ICON the Contract Research Organization (CRO) that is helping to conduct the study or are directly related to anyone that works for the Sponsor or any of their subsidiaries, the study surgeon, or the CRO

2. Follow-up Schedule

All subjects were scheduled to return for follow-up visits at 3-6 weeks and annually for 10 years after breast implant surgery. Quality of Life assessments occur at baseline, 1, 2, 3, 5, 7, and 10-year follow-up visits. A subgroup of subjects was scheduled to undergo MRI scanning to screen for silent rupture (MRI Cohort), at 1, 2, 3, 5, 7, and 10 years. Adverse events and complications were recorded at all visits as well as any unscheduled visits.

3. Clinical Endpoints

The assessment of safety was based on the total adverse event rate (“any complication)” through three years of follow-up. The study collected data to support the assessments of effectiveness based

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on patient satisfaction (5-point Likert scale and BREAST-Q®), physician satisfaction (5-point Likert scale), changes in breast measurements (primary augmentation only), and the patient's quality of life with their overall health, self-esteem, and body esteem. The questionnaires used to collect this information included the BREAST-Q® Augmentation Module (pre/post-operative) version 2.0: Satisfaction With Breasts, Rosenberg Self-Esteem Scale, SF-36v2SF Health Survey, and Body Esteem Scales. The results provided here represent three years of data.

## 4. Statistical Analysis Plan

The clinical study data collected was used to produce safety and effectiveness analyses. The risk of occurrence of safety endpoints were estimated using Kaplan-Meier analyses. Reasons for reoperations and explantations were analyzed to provide frequency distributions.

Effectiveness analyses include an analysis of subject satisfaction based on the 5-point Likert scale and two secondary effectiveness endpoints, patient's satisfaction with their breasts based on the BREAST-Q® Augmentation Module version 2.0 Satisfaction with Breasts questionnaire, and Physician Satisfaction with the implant based on the 5-point Likert scale. BREAST-Q Augmentation Module 2.0 Satisfaction with Breasts at baseline was collected from 156 (35%) of primary augmentation and 13 (12%) of revision augmentation participants.

Additionally, responses to the various quality of life scales (Rosenberg Self-Esteem Scale, SF-36v2SF Health Survey, and Body Esteem Scales) were tabulated for a comparison analysis between pre-implantation and post- implantation results. For the Primary Augmentation cohort, an assessment of chest circumference change via Breast Measurements (Net Chest Circumference and Hemi-Circumference) from baseline was also performed.

The results through 3 years are reported, although the study remains ongoing. Data will continue to be analyzed and reported to FDA at regular study intervals. In addition, Motiva USA will periodically update labeling as more data and information become available.

## B. Accountability of PMA Cohorts

### 1. Overall Accountability

Study visit compliance is presented in Table 7. Follow-up through 3 years was 92.4% (415/449) for the primary augmentation cohort and 88.7% (94/106) for the revision augmentation cohort, for an overall 91.7% (509/555) follow-up rate. Compliance was calculated by visit type and based on the number of subjects who followed up divided by the number of subjects expected for a visit. The number of expected subjects were calculated as all theoretically due (based on implantation date and visit type) minus those who have died or been explanted and replaced with at least one non-study device. However, there were 11 patients in the Primary Augmentation cohort and 7 in the Revision Augmentation cohort who followed up late outside the target follow-up visit window.

Compliance details are provided in the table below.

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Table 7: Subject Follow-up Compliance by Cohort

| | By-Subject | | |
| --- | --- | --- | --- |
| Accounting by Window | Primary Augmentation (N=451) | Revision Augmentation (N=109) | Overall Augmentation (N=560) |
| Week 3-6 | | | |
| Due[1] | 451 | 109 | 560 |
| Discontinued | | | |
| Deaths | 0 | 0 | 0 |
| Explanted with Non-Study Replacement | 0 | 0 | 0 |
| Subject Request | 0 | 0 | 0 |
| Lost-to-Follow-up | 0 | 0 | 0 |
| Other | 0 | 0 | 0 |
| Seen | 446 | 109 | 555 |
| Expected[2] | 451 | 109 | 560 |
| % Compliant out of Expected | 98.9% | 100.0% | 99.1% |
| Year 1 | | | |
| Due[1] | 451 | 109 | 560 |
| Discontinued | | | |
| Deaths | 0 | 1 | 1 |
| Explanted with Non-Study Replacement | 1 | 0 | 1 |
| Subject Request | 1 | 1 | 2 |
| Lost-to-Follow-up | 0 | 0 | 0 |
| Other | 0 | 0 | 0 |
| Seen | 437 | 101 | 538 |
| Expected[2] | 450 | 108 | 558 |
| % Compliant out of Expected | 97.1% | 93.5% | 96.4% |
| Year 2 | | | |
| Due[1] | 451 | 109 | 560 |
| Discontinued | | | |
| Deaths | 1 | 1 | 2 |
| Explanted with Non-Study Replacement | 1 | 2 | 3 |
| Subject Request | 2 | 2 | 4 |
| Lost-to-Follow-up | 1 | 0 | 1 |
| Other | 0 | 0 | 0 |
| Seen | 428 | 94 | 522 |
| Expected[2] | 449 | 106 | 555 |
| % Compliant out of Expected | 95.3% | 88.7% | 94.1% |
| Year 3 | | | |
| Due[1] | 451 | 109 | 560 |
| Discontinued | | | |
| Deaths | 1 | 1 | 2 |
| Explanted with Non-Study Replacement | 1 | 2 | 3 |
| Subject Request | 2 | 2 | 4 |
| Lost-to-Follow-up | 2 | 0 | 2 |
| Other | 0 | 0 | 0 |
| Seen | 415 | 94 | 509 |
| Expected[2] | 449 | 106 | 555 |

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| | By-Subject | | |
| --- | --- | --- | --- |
| Accounting by Window | Primary Augmentation (N=451) | Revision Augmentation (N=109) | Overall Augmentation (N=560) |
| % Compliant out of Expected | 92.4% | 88.7% | 91.7% |
| | | | |

[1] "Due" is calculated based on per-protocol follow-up schedule.
[2] "Expected" indicates the number "Due" minus discontinuations due to death or replacement with non-study.

## 2. MRI Cohort Accountability

For the augmentation MRI cohort, a total of two hundred and eighteen (218) subjects enrolled. Table 8 presents subject compliance for this sub-study cohort.

Table 8: MRI Cohort Follow-up Compliance by Cohort

| | By-Subject | | |
| --- | --- | --- | --- |
| Accounting by Window | Primary Augmentation (N=176) | Revision Augmentation (N=42) | Overall Augmentation (N=218) |
| | | | |
| Year 1 | | | |
| Due | 176 | 42 | 218 |
| Discontinued | | | |
| Claustrophobic | 2 | 1 | 3 |
| Deaths | 0 | 0 | 0 |
| Primary Devices Removed | 1 | 0 | 1 |
| Unavailable | 2 | 2 | 4 |
| Subject Decision | 2 | 0 | 2 |
| Seen | 160 | 37 | 197 |
| Expected[1] | 175 | 42 | 217 |
| % Compliant out of Expected | 91.4% | 88.1% | 90.8% |
| Year 2 | | | |
| Due | 176 | 42 | 218 |
| Discontinued | | | |
| Claustrophobic | 3 | 2 | 5 |
| Deaths | 0 | 0 | 0 |
| Primary Devices Removed | 2 | 4 | 6 |
| Unavailable | 7 | 0 | 7 |
| Subject Decision | 2 | 0 | 2 |
| Seen | 149 | 32 | 181 |
| Expected[1] | 174 | 38 | 212 |
| % Compliant out of Expected | 85.6% | 84.2% | 85.4% |
| Year 3 | | | |
| Due | 176 | 42 | 218 |
| Discontinued | | | |
| Claustrophobic | 5 | 2 | 7 |
| Deaths | 0 | 0 | 0 |
| Primary Devices Removed | 2 | 5 | 7 |

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| | By-Subject | | |
| --- | --- | --- | --- |
| Accounting by Window | Primary Augmentation (N=176) | Revision Augmentation (N=42) | Overall Augmentation (N=218) |
| Unavailable | 7 | 2 | 9 |
| Subject Decision | 2 | 0 | 2 |
| Seen | 142 | 30 | 172 |
| Expected[1] | 174 | 37 | 211 |
| % Compliant out of Expected | 81.6% | 81.1% | 81.5% |
| | | | |

Note: "Unavailable" includes subjects who were pregnant or who had other temporary medical conditions/circumstances preventing an MRI scan.
[1] "Expected" indicates the number "Due" minus discontinuation due to death or device removal.

## C. Study Population, Demographics, and Baseline Parameters

Within the augmentation cohorts, subject ages ranged from 22-68 years, and 86.6% of the study subjects are Caucasian. Almost all (90%) of the study subjects have at least some college education. Additional demographic and baseline characteristics for all implanted subjects are presented by indication in Table 9 below.

Table 9: Demographics by Cohort

| | By-Subject | |
| --- | --- | --- |
| Characteristic | Primary Augmentation (N=451) | Revision Augmentation (N=109) |
| Age Group | | |
| 22-29 years | 155 (34.4%) | 6 (5.5%) |
| 30-39 years | 207 (45.9%) | 35 (32.1%) |
| 40-49 years | 75 (16.6%) | 28 (25.7%) |
| 50-59 years | 13 (2.9%) | 33 (30.3%) |
| 60-69 years | 1 (0.2%) | 7 (6.4%) |
| 70+ years | 0.0% | 0.0% |
| | | |
| Age (years) | | |
| Mean (SD) | 33.5 (7.49) | 44.5 (10.52) |
| Median (Min-Max) | 33.0 (22-60) | 44.0 (24-68) |
| | | |
| Body Mass Index (kg/m²) | | |
| Mean (SD) | 22.0 (2.84) | 22.5 (2.91) |
| Median (Min-Max) | 21.5 (17-35) | 22.1 (18-35) |
| | | |
| Race | | |
| American Indian or Alaska Native | 1 (0.2%) | 0.0% |
| Asian | 28 (6.2%) | 4 (3.7%) |
| Black | 9 (2.0%) | 0.0% |
| Native Hawaiian or Other Pacific Islander | 1 (0.2%) | 2 (1.8%) |

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| | By-Subject | |
| --- | --- | --- |
| Characteristic | Primary Augmentation (N=451) | Revision Augmentation (N=109) |
| White | 389 (86.3%) | 96 (88.1%) |
| Other | 23 (5.1%) | 7 (6.4%) |
| | | |
| Education | | |
| Less than high school | 2 (0.4%) | 2 (1.8%) |
| High School/GED | 38 (8.4%) | 14 (12.8%) |
| Some College/Vocational School | 113 (25.1%) | 22 (20.2%) |
| College Graduate | 202 (44.8%) | 52 (47.7%) |
| Post-Graduate Education | 96 (21.3%) | 19 (17.4%) |
| | | |
| Marital Status | | |
| Divorced | 49 (10.9%) | 18 (16.5%) |
| Married | 218 (48.3%) | 60 (55.0%) |
| Separated | 5 (1.1%) | 1 (0.9%) |
| Single | 176 (39.0%) | 27 (24.8%) |
| Widowed | 3 (0.7%) | 3 (2.8%) |

Several differences in demographics trends between the three OUS sites and 20 US sites were observed. There were no revision augmentation patients in the OUS sites and the number of patients was small (n=49). Compared to the OUS sites, the US population tended to be implanted with larger volume devices (57% US versus 40% OUS in the 305cc-500 cc range), was more likely to be married (52% US versus 20% OUS), and was older at the time of implantation (27% US versus 47% OUS in the 22-29-year age range). Demographic trends for race were similar between OUS and US.

Additionally, US subjects were less likely to be implanted with devices containing RFID than OUS subjects (21% versus 100%). This difference may be due to the patient and surgeon preferences and familiarity of implants with the RFID at OUS versus US sites.

The following two tables show the Operative Characteristics by Cohort (Table 10) and Implant Characteristics by Cohort (Table 11).

For the primary augmentation subjects, the inframammary incision site (85.3%) and the submuscular/dual plane surgical placement (94.6%) were the most common surgical approaches. The Round Ergonomix implants represented 88.7% of implants used.

For the revision-augmentation subjects, 78.9% and 81.7% of the subjects underwent submuscular and inframammary approaches, respectively. The Round Ergonomix implants represented 87.2% of the devices used.

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Table 10: Operative Characteristics by Cohort

| Characteristic | Primary Augmentation (N=901) | Revision Augmentation (N=218) | Overall Augmentation (N=1119) |
| --- | --- | --- | --- |
| Incision Site | | | |
| Inframammary | 769 (85.3%) | 178 (81.7%) | 947 (84.6%) |
| Mastopexy | 20 (2.2%) | 14 (6.4%) | 34 (3.0%) |
| Periareolar | 26 (2.9%) | 22 (10.1%) | 48 (4.3%) |
| Transaxillary | 86 (9.5%) | 4 (1.8%) | 90 (8.0%) |
| Placement | | | |
| Complete muscle coverage | 24 (2.7%) | 4 (1.8%) | 28 (2.5%) |
| Partial sub-muscular/Dual plane | 852 (94.6%) | 172 (78.9%) | 1024 (91.5%) |
| Sub-fascial | 5 (0.6%) | 4 (1.8%) | 9 (0.8%) |
| Subglandular | 20 (2.2%) | 38 (17.4%) | 58 (5.2%) |
| Incision Length (cm) | | | |
| Mean (SD) | 4.2 (1.69) | 5.7 (3.14) | 4.5 (2.12) |
| Median (Min-Max) | 4.0 (2-17) | 5.0 (3-30) | 4.0 (2-30) |

Table 11: Implant Characteristics by Cohort

| Device Style | By-Implant | |
| --- | --- | --- |
| | Primary Augmentation (N=901) | Revision Augmentation (N=218) |
| Device Style | | |
| Round | 102 (11.3%) | 28 (12.8%) |
| Round Ergonomix | 799 (88.7%) | 190 (87.2%) |
| Radiofrequency Identification Device (RFID) | | |
| With RFID | 270 (30.0%) | 38 (17.4%) |
| Without RFID | 631 (70.0%) | 180 (82.6%) |

## D. Safety and Effectiveness Results

### 1. Safety Results

The key safety outcomes for this study are presented below.

#### a. Complication Rates

Table 12 below shows the 3-year, by-subject Kaplan-Meier (KM) risk rates of first occurrence

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(95% confidence interval) of complications for the two study cohorts. The most common complication through 3 years for both cohorts (primary augmentation and revision augmentation) were reoperation (6.1% and 25.8%). Implant Malposition (3.2%) and explantation with or without replacement (1.6%) were the next two most frequently reported events for the primary augmentation cohort. For revision augmentation, explantation with or without replacement (16.5%) and capsular contracture III/IV (6.7%) were the most frequently reported events.

Thirty-seven (37) primary augmentation subjects experienced at least one complication or reoperation through 3 years, resulting in an Any Complication rate of $8.4\%$ . Thirty (30) revision augmentation subjects experienced at least one complication or reoperation through 3 years, resulting in an Any Complication rate of $28.4\%$ .

Table 12: KM Risk Rates of Local Complications Through 3 Years

| | Primary Augmentation | | Revision Augmentation | |
| --- | --- | --- | --- | --- |
| | By-Subject (N=451) | | By-Subject (N=109) | |
| KM Rates Through 3 Years | Kaplan Meier Risk | 95% CI | Kaplan Meier Risk | 95% CI |
| Any Complication (including reoperations) | 8.4% | 6.1%, 11.4% | 28.4% | 20.8%, 38.0% |
| Any Reoperation | 6.1% | 4.3%, 8.8% | 25.8% | 18.5%, 35.4% |
| Explantation (with/without replacement) | 1.6% | 0.8%, 3.3% | 16.5% | 10.6%, 25.1% |
| Explantation with Replacement | 1.4% | 0.6%, 3.0% | 13.8% | 8.4%, 22.2% |
| Explantation without Replacement | 0.2% | 0.0%, 1.6% | 2.9% | 0.9%, 8.7% |
| Animation Deformity | 0.2% | 0.0%, 1.6% | 0.0% | 0.0% |
| Asymmetry | 0.2% | 0.0%, 1.6% | 3.9% | 1.5%, 10.0% |
| Breast Implant-Associated ALCL | 0.0% | 0.0% | 0.0% | 0.0% |
| Breast Pain | 0.7% | 0.2%, 2.1% | 1.0% | 0.1%, 6.6% |
| Breast Tissue Atrophy | 0.2% | 0.0%, 1.6% | 0.0% | 0.0% |
| Breast/Skin Sensation Changes | 0.0% | 0.0% | 0.0% | 0.0% |
| Calcification | 0.0% | 0.0% | 0.0% | 0.0% |
| Cancer-Breast (New) | 0.0% | 0.0% | 0.0% | 0.0% |
| Cancer-Breast (Recurrence) | 0.0% | 0.0% | 0.0% | 0.0% |
| Capsular Contracture II with surgical Intervention | 0.2% | 0.0%, 1.6% | 1.9% | 0.5%, 7.4% |
| Capsular Contracture III/IV | 0.5% | 0.1%, 1.8% | 6.7% | 3.2%, 13.5% |
| Capsular Contracture III | 0.2% | 0.0%, 1.6% | 5.7% | 2.6%, 12.3% |
| Capsular Contracture IV | 0.2% | 0.0%, 1.6% | 1.0% | 0.1%, 6.6% |
| Delayed Wound Healing | 0.2% | 0.0%, 1.6% | 0.0% | 0.0% |
| Double Capsule | 0.0% | 0.0% | 1.0% | 0.1%, 6.6% |
| Fibrocystic Disease | 0.0% | 0.0% | 0.0% | 0.0% |
| Galactorrhea | 0.0% | 0.0% | 0.0% | 0.0% |
| Granuloma | 0.0% | 0.0% | 0.0% | 0.0% |
| Hematoma | 0.7% | 0.2%, 2.1% | 1.8% | 0.5%, 7.1% |
| Hypertrophic/Abnormal Scarring | 0.2% | 0.0%, 1.6% | 0.0% | 0.0% |
| Iatrogenic Injury to Implant | 0.0% | 0.0% | 1.0% | 0.1%, 6.6% |
| Implant Extrusion | 0.0% | 0.0% | 1.0% | 0.1%, 6.6% |
| Implant Malposition | 3.2% | 1.9%, 5.3% | 4.9% | 2.1%, 11.3% |
| Implant Palpability/Visibility | 0.2% | 0.0%, 1.6% | 0.0% | 0.0% |

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b. Primary Reason for Reoperation

Table 13 below shows the primary reasons for reoperations, stratified by indication through 3 years. The rates are based on the total number of reoperations for each indication.

Table 13: Primary Reason for Reoperation

| | Primary Augmentation | Revision Augmentation |
| --- | --- | --- |
| Infection | 2 (6.9%) | 1 (3.4%) |
| Capsular Contracture | 3 (10.3%) | 6 (20.7%) |
| Implant Extrusion | 0 | 1 (3.4%) |
| Hematoma | 3 (10.3%) | 4 (13.8%) |
| Breast Pain | 0 | 1 (3.4%) |
| Implant Malposition | 13 (44.8%) | 2 (6.9%) |
| Animation Deformity | 1 (3.4%) | 0 |
| Upper Pole Fullness | 0 | 1 (3.4%) |
| Asymmetry | 1 (3.4%) | 1 (3.4%) |

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| Ptosis | 1 (3.4%) | 5 (17.2%) |
| --- | --- | --- |
| Hypertrophic/Abnormal Scarring | 2 (6.9%) | 1 (3.4%) |
| Mass/Cyst/Lump | 1 (3.4%) | 0 |
| Size Change/Subject Choice | 2 (6.9%) | 6 (20.7%) |
| | | |
| Total Number of Reoperations | 29 (100%) | 29 (100%) |
| | | |

*Some reoperations were performed for multiple reasons; the primary reason is provided in the table.

c. Primary Reason for Implant Removal

Table 14 shows the main reasons for implant removal, stratified by indication, through 3 years. The rates are based on the total number of explantations for that indication.

Table 14: Primary Reason for Implant Removal

| | Primary Augmentation | Revision Augmentation |
| --- | --- | --- |
| | | |
| Infection | 1 (7.7%) | 1 (3.6%) |
| Capsular Contracture | 5 (38.5%) | 7 (25.0%) |
| Implant Extrusion | 0 | 1 (3.6%) |
| Breast Pain | 0 | 2 (7.1%) |
| Implant Malposition | 1 (7.7%) | 1 (3.6%) |
| Asymmetry | 0 | 2 (7.1%) |
| Ptosis | 0 | 2 (7.1%) |
| Size Change/Subject Choice | 6 (46.2%) | 12 (42.9%) |
| | | |
| Total Number of Explantations | 13 (100%) | 28 (100%) |
| | | |

d. Other Clinical Safety Outcomes

The following data describes the clinical findings from the study regarding connective tissue disease (CTD), CTD signs and symptoms, cancer, reproductive complications, lactation complications, and suicide.

CTD Diagnoses

CTD diagnoses can include diseases such as fibromyalgia, systemic lupus erythematosus (SLE), discoid lupus, and scleroderma. Through Year 3, no primary augmentation and no revision augmentation subjects have been diagnosed with a CTD.

CTD Signs and Symptoms

Self-reported signs and symptoms were collected at follow-up visits only. The symptoms that were collected were: lymphadenopathy, abnormal bruising or bleeding, purpura, ecchymoses, petechia,

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arthralgias, joint swelling for more than six (6) weeks, morning stiffness that lasts more than 30 minutes, muscle weakness, myalgias, paresthesia, cognitive dysfunction, peripheral neuropathy, memory problems, ocular inflammation/retinitis/optic neuritis, neuralgias, pleurisy, respiratory difficulty, hair loss, facial rash, photosensitivity, skin rash, urticaria, telangiectasia, pruritis, depression, unexplained fever, dizziness, dry eyes, dry mouth, fatigue, and generalized pain.

For primary augmentation subjects, through 3 years, the risk of experiencing any of the symptoms after implantation is 6.1%. For revision augmentation subjects, through 3 years, the risk of experiencing any of the symptoms after implantation is 5.3%. For both, general (depression, unexplained fever, dizziness, dry eyes, dry mouth, fatigue, generalized pain) and skin-related (e.g., hair loss, facial rash, photosensitivity, skin rash, urticaria, telangiectasia, pruritis) signs and symptoms were the most common. Of note, CTD sign/symptoms were not collected at baseline (prior to implantation); therefore, the risk estimates for symptoms may be biased upwards because they also include reports that were present prior to implantation.

## Cancer

For primary augmentation and revision augmentation subjects, through 3 years, there were no cases of breast cancer identified and no cases of fibrocystic breast disease. Diagnoses of any other (non-breast) cancers have been reported in 2 subjects (less than 1%) in the primary augmentation cohort through 3 years.

## Breast Implant Associated - Anaplastic Large Cell Lymphoma

There were no reports of breast implant associated-anaplastic large cell lymphoma (BIA-ALCL) in any of the subject cohorts.

## Lactation Complications

For the primary augmentation subjects, 48.6% attempted breastfeeding with no difficulties, 42.6% never attempted to breastfeed, 7.8% had preoperative difficulties, and 1.1% had postoperative difficulties through 3 years.

For the revision augmentation subjects, 49.5% attempted breastfeeding with no difficulty, 41.3% never attempted breastfeeding, 9.2% reported preoperative difficulties, and 0.0% had postoperative difficulties through 3 years.

## Reproduction Complications

For the primary augmentation subjects, 2.4% of subjects reported at least 1 reproductive complication through 3 years. Complications reported include infertility (0.4%), miscarriage (1.6%), termination due to medical reasons (0.2%), uterine bleeding (0.2%), and ovarian cyst (0.2%).

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For the revision augmentation subjects, 1.8% of subjects through 3 years reported reproductive issues. The reproductive issues include both preeclampsia and termination due to medical reasons, each at 0.9%.

## Suicide

There are no reports of suicide in any of the cohorts.

## Non-local complications

For the primary augmentation cohort, the non-local complications reported through 3 years included: cardiovascular, COVID-19, death (rectal cancer complications), gastrointestinal, musculoskeletal, tonsillitis, trauma-non breast, urinary tract infection, and other infections (sepsis), (all reported less than 1%).

For the revision augmentation cohort, the non-local complications reported through 3 years included: death (brain hemorrhage due to fall), gastrointestinal, leukemia, musculoskeletal, trauma-non breast, pulmonary embolism, and allergic reaction (all reported less than 2%).

e. Cumulative Risk for Occurrence of Each Complication at Each Follow-Up Assessment Point

The cumulative risk for the first occurrence of each complication at each follow-up time point is presented below in Table 15. The percentages represent Kaplan-Meier risk rates.

Table 15: Cumulative Risk for Occurrence Through 3 Years for All Time Points by Cohort

| | Study Cohort | |
| --- | --- | --- |
| Complication | Primary Augmentation | Revision Augmentation |
| Any Complication | | |
| Week 6 | 2.7% | 5.5% |
| Year 1 | 6.3% | 21.6% |
| Year 2 | 8.1% | 25.4% |
| Year 3 | 8.4% | 28.4% |
| Any Reoperation | | |
| Week 6 | 1.3% | 4.6% |
| Year 1 | 4.5% | 15.1% |
| Year 2 | 5.7% | 23.8% |
| Year 3 | 6.1% | 25.8% |
| Explantation (with/without replacement) | | |
| Week 6 | 0.2% | 0.9% |
| Year 1 | 1.1% | 6.6% |
| Year 2 | 1.6% | 15.5% |
| Year 3 | 1.6% | 16.5% |
| Explantation with Replacement | | |

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| | Study Cohort | |
| --- | --- | --- |
| Complication | Primary Augmentation | Revision Augmentation |
| Week 6 | 0.0% | 0.0% |
| Year 1 | 0.9% | 4.8% |
| Year 2 | 1.4% | 12.8% |
| Year 3 | 1.4% | 13.8% |
| Explantation without Replacement | | |
| Week 6 | 0.2% | 0.9% |
| Year 1 | 0.2% | 1.9% |
| Year 2 | 0.2% | 2.9% |
| Year 3 | 0.2% | 2.9% |
| Animation Deformity | | |
| Week 6 | 0.0% | 0.0% |
| Year 1 | 0.0% | 0.0% |
| Year 2 | 0.2% | 0.0% |
| Year 3 | 0.2% | 0.0% |
| Asymmetry | | |
| Week 6 | 0.0% | 0.0% |
| Year 1 | 0.2% | 2.9% |
| Year 2 | 0.2% | 3.9% |
| Year 3 | 0.2% | 3.9% |
| Breast Implant-Associated ALCL | | |
| Week 6 | 0.0% | 0.0% |
| Year 1 | 0.0% | 0.0% |
| Year 2 | 0.0% | 0.0% |
| Year 3 | 0.0% | 0.0% |
| Breast Pain | | |
| Week 6 | 0.0% | 0.0% |
| Year 1 | 0.2% | 1.0% |
| Year 2 | 0.7% | 1.0% |
| Year 3 | 0.7% | 1.0% |
| Breast Tissue Atrophy | | |
| Week 6 | 0.2% | 0.0% |
| Year 1 | 0.2% | 0.0% |
| Year 2 | 0.2% | 0.0% |
| Year 3 | 0.2% | 0.0% |
| Breast/Skin Sensation Changes | | |
| Week 6 | 0.0% | 0.0% |
| Year 1 | 0.0% | 0.0% |
| Year 2 | 0.0% | 0.0% |
| Year 3 | 0.0% | 0.0% |
| Calcification | | |

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| | Study Cohort | |
| --- | --- | --- |
| Complication | Primary Augmentation | Revision Augmentation |
| Week 6 | 0.0% | 0.0% |
| Year 1 | 0.0% | 0.0% |
| Year 2 | 0.0% | 0.0% |
| Year 3 | 0.0% | 0.0% |
| Cancer-Breast (New) | | |
| Week 6 | 0.0% | 0.0% |
| Year 1 | 0.0% | 0.0% |
| Year 2 | 0.0% | 0.0% |
| Year 3 | 0.0% | 0.0% |
| Cancer-Breast (Recurrence) | | |
| Week 6 | 0.0% | 0.0% |
| Year 1 | 0.0% | 0.0% |
| Year 2 | 0.0% | 0.0% |
| Year 3 | 0.0% | 0.0% |
| Capsular Contracture II with Surgical Intervention | | |
| Week 6 | -- | -- |
| Year 1 | 0.2% | 1.9% |
| Year 2 | 0.2% | 1.9% |
| Year 3 | 0.2% | 1.9% |
| Capsular Contracture III/IV | | |
| Week 6 | -- | -- |
| Year 1 | 0.2% | 6.7% |
| Year 2 | 0.5% | 6.7% |
| Year 3 | 0.5% | 6.7% |
| Capsular Contracture III | | |
| Week 6 | 0.0% | 0.0% |
| Year 1 | 0.0% | 5.7% |
| Year 2 | 0.2% | 5.7% |
| Year 3 | 0.2% | 5.7% |
| Capsular Contracture IV | | |
| Week 6 | 0.0% | 0.0% |
| Year 1 | 0.2% | 1.0% |
| Year 2 | 0.2% | 1.0% |
| Year 3 | 0.2% | 1.0% |
| Delayed Wound Healing | | |
| Week 6 | 0.2% | 0.0% |
| Year 1 | 0.2% | 0.0% |
| Year 2 | 0.2% | 0.0% |
| Year 3 | 0.2% | 0.0% |
| Double Capsule | | |

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| | Study Cohort | |
| --- | --- | --- |
| Complication | Primary Augmentation | Revision Augmentation |
| Week 6 | 0.0% | 0.0% |
| Year 1 | 0.0% | 1.0% |
| Year 2 | 0.0% | 1.0% |
| Year 3 | 0.0% | 1.0% |
| Fibrocystic Disease | | |
| Week 6 | 0.0% | 0.0% |
| Year 1 | 0.0% | 0.0% |
| Year 2 | 0.0% | 0.0% |
| Year 3 | 0.0% | 0.0% |
| Galactorrhea | | |
| Week 6 | 0.0% | 0.0% |
| Year 1 | 0.0% | 0.0% |
| Year 2 | 0.0% | 0.0% |
| Year 3 | 0.0% | 0.0% |
| Granuloma | | |
| Week 6 | 0.0% | 0.0% |
| Year 1 | 0.0% | 0.0% |
| Year 2 | 0.0% | 0.0% |
| Year 3 | 0.0% | 0.0% |
| Hematoma | | |
| Week 6 | 0.7% | 1.8% |
| Year 1 | 0.7% | 1.8% |
| Year 2 | 0.7% | 1.8% |
| Year 3 | 0.7% | 1.8% |
| Hypertrophic/Abnormal Scarring | | |
| Week 6 | 0.0% | 0.0% |
| Year 1 | 0.0% | 0.0% |
| Year 2 | 0.2% | 0.0% |
| Year 3 | 0.2% | 0.0% |
| Iatrogenic Injury to Implant | | |
| Week 6 | 0.0% | 0.0% |
| Year 1 | 0.0% | 1.0% |
| Year 2 | 0.0% | 1.0% |
| Year 3 | 0.0% | 1.0% |
| Implant Extrusion | | |
| Week 6 | 0.0% | 0.0% |
| Year 1 | 0.0% | 1.0% |
| Year 2 | 0.0% | 1.0% |
| Year 3 | 0.0% | 1.0% |
| Implant Malposition | | |

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| | Study Cohort | |
| --- | --- | --- |
| Complication | Primary Augmentation | Revision Augmentation |
| Week 6 | 0.2% | 0.9% |
| Year 1 | 2.7% | 3.8% |
| Year 2 | 3.2% | 3.8% |
| Year 3 | 3.2% | 4.9% |
| Implant Palpability/Visibility | | |
| Week 6 | 0.0% | 0.0% |
| Year 1 | 0.0% | 0.0% |
| Year 2 | 0.2% | 0.0% |
| Year 3 | 0.2% | 0.0% |
| Implant Rotation | | |
| Week 6 | 0.0% | 0.0% |
| Year 1 | 0.0% | 0.0% |
| Year 2 | 0.0% | 0.0% |
| Year 3 | 0.0% | 0.0% |
| Infection | | |
| Week 6 | 0.9% | 0.9% |
| Year 1 | 0.9% | 0.9% |
| Year 2 | 0.9% | 0.9% |
| Year 3 | 0.9% | 0.9% |
| Inflammation | | |
| Week 6 | 0.0% | 0.0% |
| Year 1 | 0.0% | 0.0% |
| Year 2 | 0.0% | 0.0% |
| Year 3 | 0.0% | 0.0% |
| Irritation | | |
| Week 6 | 0.0% | 0.0% |
| Year 1 | 0.0% | 0.0% |
| Year 2 | 0.0% | 0.0% |
| Year 3 | 0.0% | 0.0% |
| Mass/Cyst/Lump | | |
| Week 6 | 0.0% | 0.0% |
| Year 1 | 0.0% | 0.0% |
| Year 2 | 0.2% | 0.0% |
| Year 3 | 0.2% | 2.4% |
| Ptosis | | |
| Week 6 | 0.0% | 0.0% |
| Year 1 | 0.2% | 3.8% |
| Year 2 | 0.2% | 4.8% |
| Year 3 | 0.2% | 4.8% |
| Redness | | |

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| | Study Cohort | |
| --- | --- | --- |
| Complication | Primary Augmentation | Revision Augmentation |
| Week 6 | 0.0% | 0.0% |
| Year 1 | 0.0% | 0.0% |
| Year 2 | 0.0% | 0.0% |
| Year 3 | 0.0% | 0.0% |
| Rupture (Suspected/Confirmed) - All | | |
| Week 6 | 0.0% | 0.0% |
| Year 1 | 0.0% | 0.0% |
| Year 2 | 0.6% | 0.0% |
| Year 3 | 0.6% | 0.0% |
| Rupture (Suspected/Confirmed) - MRI cohort | | |
| Week 6 | 0.0% | 0.0% |
| Year 1 | 0.0% | 0.0% |
| Year 2 | 0.6% | 0.0% |
| Year 3 | 0.6% | 0.0% |
| Rupture (Suspected/Confirmed) - Non-MRI cohort | | |
| Week 6 | 0.0% | 0.0% |
| Year 1 | 0.0% | 0.0% |
| Year 2 | 0.0% | 0.0% |
| Year 3 | 0.0% | 0.0% |
| Seroma - All | | |
| Week 6 | 0.0% | 0.0% |
| Year 1 | 0.0% | 0.0% |
| Year 2 | 0.0% | 0.0% |
| Year 3 | 0.0% | 0.0% |
| Seroma - Early (less than 1 year) | | |
| Week 6 | 0.0% | 0.0% |
| Year 1 | 0.0% | 0.0% |
| Year 2 | 0.0% | 0.0% |
| Year 3 | 0.0% | 0.0% |
| Seroma - Late | | |
| Week 6 | 0.0% | 0.0% |
| Year 1 | 0.0% | 0.0% |
| Year 2 | 0.0% | 0.0% |
| Year 3 | 0.0% | 0.0% |
| Nipple Complications | | |
| Week 6 | 0.0% | 0.0% |
| Year 1 | 0.0% | 0.0% |
| Year 2 | 0.2% | 0.0% |
| Year 3 | 0.2% | 0.0% |
| Nipple Sensation Changes | | |

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| | Study Cohort | |
| --- | --- | --- |
| Complication | Primary Augmentation | Revision Augmentation |
| Week 6 | 0.0% | 0.0% |
| Year 1 | 0.0% | 0.0% |
| Year 2 | 0.0% | 0.0% |
| Year 3 | 0.0% | 0.0% |
| RFID Failure | | |
| Week 6 | 0.0% | 0.0% |
| Year 1 | 0.0% | 0.0% |
| Year 2 | 0.0% | 0.0% |
| Year 3 | 0.0% | 0.0% |
| Skin Rash | | |
| Week 6 | 0.2% | 0.0% |
| Year 1 | 0.2% | 0.0% |
| Year 2 | 0.2% | 0.0% |
| Year 3 | 0.2% | 0.0% |
| Skin Related | | |
| Week 6 | 0.0% | 0.0% |
| Year 1 | 0.0% | 0.0% |
| Year 2 | 0.0% | 0.0% |
| Year 3 | 0.0% | 0.0% |
| Swelling | | |
| Week 6 | 0.0% | 0.0% |
| Year 1 | 0.0% | 0.0% |
| Year 2 | 0.0% | 0.0% |
| Year 3 | 0.0% | 0.0% |
| Tissue or Skin Necrosis | | |
| Week 6 | 0.0% | 0.0% |
| Year 1 | 0.0% | 0.0% |
| Year 2 | 0.0% | 0.0% |
| Year 3 | 0.0% | 0.0% |
| Upper Pole Fullness | | |
| Week 6 | 0.0% | 0.0% |
| Year 1 | 0.0% | 0.0% |
| Year 2 | 0.0% | 0.0% |
| Year 3 | 0.0% | 0.0% |
| Wrinkling/Rippling | | |
| Week 6 | 0.0% | 0.0% |
| Year 1 | 0.0% | 0.0% |
| Year 2 | 0.5% | 0.0% |
| Year 3 | 0.5% | 0.0% |
| Other-Local Event | | |

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| | Study Cohort | |
| --- | --- | --- |
| Complication | Primary Augmentation | Revision Augmentation |
| Week 6 | 0.0% | 0.0% |
| Year 1 | 0.0% | 0.0% |
| Year 2 | 0.0% | 0.0% |
| Year 3 | 0.0% | 0.0% |

f. Risk Factor Analysis

A risk factor analysis was performed to determine whether there were any risk factors associated with the reported complications. In the primary augmentation cohort, four adverse event types with at least 10 events were reported and examined (Any Complication, Reoperation, Explantation, and Implant Malposition).

- Implant projection was identified as a risk factor for Explantation, Reoperation, and Any Complication; subjects who received implants with Corsé or Full projections were more likely to undergo reoperation than those who received implants with Demi or Mini projections.
- In addition, pre-operative medication use was also found to be a risk factor for reoperation; subjects who reported taking at least one medication in the 3 months prior to implantation were more likely to undergo reoperation.
- Regarding implant malposition, no significant factors were found.

In the revision augmentation cohort, four adverse event types with at least 10 events were reported and examined (Any Complication, Reoperation, Explantation, and Ptosis).

- Implant placement was identified as a significant factor for three of the event types (i.e., the composite Any Complication endpoint, Ptosis, and Reoperation).
- For all three, implants placed in the sub-facial or subglandular positions were found more likely to have a complication, experience ptosis, and/or undergo reoperation than implants placed in the complete or partial/dual plane submuscular position.
- Additionally, for Ptosis, subject age was identified as a significant risk factor, with risk of ptosis decreasing as implantation age increases.
- Regarding Explantation, no significant factors were found.

2. Effectiveness Results

Effectiveness analyses include an analysis of subject satisfaction based on a 5-point Likert scale and two secondary effectiveness endpoints, patient's satisfaction using BREAST-Q® Augmentation Module version 2.0 Satisfaction with Breasts questionnaire, and Physician Satisfaction with the implant based on the 5-point Likert scale. The BREAST-Q Augmentation Module version 2.0 Satisfaction with Breasts questionnaire at baseline was collected from 156 (35%) of primary augmentation and 13 (12%) of revision augmentation participants.

Additionally, responses to the various quality of life (QOL) scales (Rosenberg Self-Esteem Scale, 36-item short form (SF-36v2SF) Health Survey, and Body Esteem Scales) were tabulated for a comparison analysis between pre-implantation and post-implantation results. For the Primary

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Augmentation cohort, an assessment of chest circumference change via Breast Measurements (Net Chest Circumference and Hemi-Circumference) from baseline was also performed.

The effectiveness outcomes for this study are presented below.

a. Primary Augmentation Subjects

At the 3 year follow-up, the majority of primary augmentation subjects (97.1%) and physicians (99.0%) were satisfied with their results based on the 5-point Likert Scale.

For the BREAST-Q® Augmentation Module version 2.0 Satisfaction with Breasts questionnaire, 156 participants completed the questionnaire at baseline with a mean score of 37.4. Of the participants (n=141 subjects) who completed questionnaires at baseline and the Year-3 visit, there was a mean increase for individual patients of 41.6 points. There was a total of 383 participants who completed the BREAST-Q® questionnaire at Year 3 (regardless of baseline completion) with a mean satisfaction score of 82.0 points. The questionnaire is a 100-point scale, with higher numbers being better.

Many subjects (90.6%) in the primary augmentation cohort reported increased bra size by at least one cup size. More (57.8%) of the subjects increased by two to five cup sizes. 3.9% decreased or did not report the change in bra size. (e.g., sports bra with different sizing, or no bra).

For primary augmentation subjects, comparisons of Baseline SF-36 QOL scores to scores at Year 3 showed some changes; there were a number of decreases in the quality of life scales. However, effect sizes were small, so the observed changes may not be clinically relevant.

For the primary augmentation cohort, the measures and mean scores from baseline to Year 3 were:

Rosenberg Self-Esteem Scale (30-point scale)
- 25.8 to 25.8

Body Esteem survey (5-point scale)
- Overall, 3.9 to 3.9
- Physical Condition, 4.2 to 4.0
- Sexual Attractiveness, 3.9 to 4.0
- Weight Concern, 3.7 to 3.6

SF-36 survey (100-point scale)
- Bodily Pain, 92.5 to 86.9
- General Health, 88.6 to 85.2
- Mental Health, 83.3 to 79.6
- Physical Functioning, 97.1 to 96.2
- Role Emotional, 95.3 to 91.8
- Role Physical, 96.5 to 94.3
- Social Functioning, 95.0 to 90.6
- Vitality, 72.9 to 66.5

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For primary augmentation subjects, mean total self-esteem scores on the Rosenberg Self-Esteem Scale at Baseline and Year 3 reported high self-esteem responses (mean values greater than 25 points) at all timepoints, including baseline. No significant changes were found between baseline and Year 3.

Mean scores on the Body Esteem Scale and subscales showed no clinically significant change from Baseline to Year 3 among women in the primary augmentation cohort. There were a number of decreases in the quality of life scales. However, effect sizes were small, so the observed changes were judged not clinically relevant.

## b. Revision Augmentation Subjects

Most revision augmentation subjects (over 87.5%) and physicians (95.5%) were satisfied with their results of their revision implant surgery based on the 5-point Likert Scale.

For the BREAST-Q® Augmentation Module version 2.0 Satisfaction with Breasts questionnaire, 13 participants completed the questionnaire at baseline with a mean score of 54.2. Of the participants (n=12 subjects) who completed questionnaires at baseline and the Year-3 visit, there was a mean increase for individual patients of 27.1 points. There was a total of 76 participants who completed the BREAST-Q® questionnaire at Year 3 (regardless of baseline completion) with a mean satisfaction score of 78.2 points. The questionnaire is a 100-point scale, with higher numbers being better.

Bra size changes were not analyzed for revision augmentation subjects. For revision augmentation subjects, comparisons of Baseline SF-36v2 scores to scores at Year 3 showed some changes. Only one of the six (i.e., Role Emotional) may be considered clinically relevant because the effect size was greater than 0.50 even though the mean score at Year 3 (93.7) was higher/better than the national norm (79.5) [3].

For the revision augmentation cohort, the measures and means scores from baseline to Year 3 were:

Rosenberg Self-Esteem Scale (30-point scale)
- 26.2 to 25.8

Body Esteem survey (5-point scale)
- Overall, 3.9 to 3.9
- Physical Condition, 4.2 to 4.1
- Sexual Attractiveness, 3.9 to 4.0
- Weight Concern, 3.8 to 3.7

SF-36 survey (100-point scale)
- Bodily Pain, 90.2 to 83.8
- General Health, 88.0 to 84.4

PMA P230005
FDA Summary of Safety and Effectiveness
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- Mental Health, 83.8 to 80.3
- Physical Functioning, 95.4 to 95.7
- Role Emotional, 97.1 to 93.7
- Role Physical, 95.6 to 94.7
- Social Functioning, 96.2 to 92.2
- Vitality, 75.6 to 70.3

For revision augmentation subjects, mean total self-esteem scores on the Rosenberg Self-Esteem Scale at Baseline and Year 3 reported high self-esteem responses (mean values greater than 25 points) at all time points, including baseline. No significant changes were found between baseline and Year 3.

Mean scores on the Body Esteem Scale and subscales showed no clinically significant change from Baseline to Year 3.

## 3. Rupture Rate and Consequences of Rupture

To assess the rupture rate and the consequences of rupture, Motiva USA performed a review of all available clinical and preclinical data. The clinical data included (a) the Motiva Implants Core Clinical Study which includes a magnetic resonance imaging (MRI) sub-study, (b) and the published literature. The preclinical data related to rupture included the retrieval study and fatigue testing.

### a. Core Clinical Study

The Motiva Implants Core Clinical Study included rupture rate data from the MRI Cohort and the non-MRI Cohort. The study enrolled an MRI Cohort who agreed to undergo serial MRI screening at 1, 2, 3, 5, 7, and 10 years to assess rates of silent rupture over time.

There is a total of 560 subjects in the Core Clinical Study, of which 218 patients are enrolled in the MRI cohort.

There are 176 primary augmentation subjects enrolled in the MRI cohort and 275 subjects in the non-MRI cohort. Through 3 years, 99.4% of subjects (99.7% of implants) had no evidence of rupture. Through Year 3, there has been 1 unconfirmed implant rupture occurring in one subject and zero confirmed implant ruptures. Of the primary augmentation subjects in the study who were not evaluated by MRI, there were zero implant ruptures reported. The 3 year risk of rupture was 0.6% by subject.

There are 42 revision augmentation subjects enrolled in the MRI cohort and 67 subjects in the non-MRI cohort. Through 3 years, all of these subjects (100%) had no evidence of rupture. Of the revision augmentation subjects in the study who were not evaluated by MRI, there were zero implant ruptures reported. The 3 year risk of rupture was 0.0% by subject.

Of note, a total of 154 subjects with RFID-containing implants (308 implants with RFID) were…