Operator's Manual - Directions for Use
NATRELLE^TM HIGHLY COHESIVE SILICONE-FILLED BREAST IMPLANTS
Allergan Medical

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Contact: Device Licensing

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Application No. 88573
Licence No. 72262

The Operator's Manual for NATRELLE^TM HIGHLY COHESIVE SILICONE-FILLED BREAST IMPLANTS has been submitted by the medical device manufacturer and is attached for your information.

The attached version is a 1-year update to the version that accompanied the device licence issued on October 20, 2006 and does not necessarily reflect the most current information for the product.

For the most up-to-date product information, please consult your health care professional.

Due to the fact that the information originated with an organization that is not subject to the Official Languages Act, the document may only appear in the language in which it was written. Translations of the document are the responsibility of the manufacturer involved.

Table of Contents

1 Introduction

1.1 Directions to the Surgeon
1.2 Information to be Discussed with the Patient

2 Device Description

3 Indications

4 Contraindications

5 Warnings

6 Precautions

7 Special Considerations and Risks to be Discussed with the Patient

7.1 Complications
7.2 Other Reported Conditions

8 Preclinical Study Information

9 Allergan Clinical Studies

9.1 Overview of Allergan's Core Study (Cohesive Round Implants)

9.1.1 Augmentation and Revision-Augmentation Patients
9.1.2 Reconstruction and Revision-Reconstruction Patients

9.2 Overview of Allergan's Pivotal Study (Highly Cohesive Shaped Implants)

9.2.1 Augmentation and Revision-Augmentation Patients
9.2.2 Reconstruction and Revision-Reconstruction Patients

10 Instructions for Use

10.1 Single Use
10.2 Product Identification
10.3 Surgical Planning
10.4 Preliminary Product Examination
10.5 Sterile Product
10.6 Method for Removing Ruptured Silicone Gel from the Surgical Pocket
10.7 Surgical Procedure Placement

11 Documentation the Physician Should Provide to the Patient

12 Additional Specific Product Information

12.1 Returned Goods Policy
12.2 Reporting and Return of Explanted Devices
12.3 ConfidencePlus^® Limited Warranties
12.4 Product Ordering

13 Literature References

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1. INTRODUCTION

1.1 DIRECTIONS TO THE SURGEON

This document contains information that is essential to the patient consultation process. Please familiarize yourself with the content of this document and resolve any questions or concerns prior to proceeding with the use of this device.

The information supplied in this Directions for Use document is intended to provide an overview of essential information about NATRELLE^TM Cohesive Silicone-Filled Breast Implants and Highly Cohesive Silicone-Filled Breast Implants, including the indications for use, contraindications, warnings, precautions, complications and summaries of clinical study results.

Patient Counseling Information
Sections of this Directions for Use document indicated by "Patient Counseling Information" contain points that the physician should review when counseling the patient about silicone-filled breast implants and breast implant surgery.

Physician Education
Allergan offers a physician education program via the Allergan Academy^TM to educate physicians on issues relevant to Allergan's breast implants. The primary goals of the Allergan Academy^TM are to convey important information to physicians from Allergan's multicenter clinical studies and implant retrieval analyses, and to ensure that physicians are equipped with the most current clinical outcome and risk information to provide to their patients. Please contact your local Allergan Aesthetics Sales Representative or the Allergan Customer Care Department for further information on the Allergan Academy^TM and other Allergan physician education initiatives.

1.2 INFORMATION TO BE DISCUSSED WITH THE PATIENT

WARNINGS, PRECAUTIONS, ADVERSE EVENTS

Patient Counseling Information
Breast implant surgery is known to provide satisfaction to patients, HOWEVER, as with any surgical procedure, it is NOT without risks. Breast implantation is an elective procedure, and the patient must be well counseled and understand the risk benefit relationship.

Each patient should receive Allergan's bilingual Patient Planner for Breast Augmentation or Reconstruction with NATRELLE^TM Silicone- Filled Breast Implants during her initial visit/consultation. The surgeon or a designated patient counselor should instruct the patient to read the patient information carefully and also discuss with the patient the warnings, precautions, and complications listed in this Directions for Use document. The physician should advise the patient of the potential complications and that medical management of serious complications may include additional surgery and explantation. Patients should understand that breast implant surgery can cause irreversible changes to the breast.

INFORMED CONSENT

Patient Counseling Information
Before making the decision to proceed with surgery the patient should be allowed sufficient time to read and adequately understand the important patient information in Allergan's Patient Planner (patient decision-making aid) on the risks, follow-up recommendations, and benefits associated with silicone gel-filled breast implant surgery.

In order to document a successful informed consent process the Patient Planner also includes an Acceptance of Risk and Consent to Surgery document that should be signed by both the patient and the surgeon and then retained in the patient's file.

2. DEVICE DESCRIPTIONS

The silicone-filled breast implants in the NATRELLE^TM Collection are constructed with barrier shell technology resulting in a low diffusion silicone elastomer shell. The Collection includes the Cohesive Silicone-Filled Breast Implants (a round implant with soft, cohesive silicone gel) and the Highly Cohesive Silicone-Filled Breast Implants (a shaped implant with more cohesive silicone gel). All styles are a single "lumen" design and consist of a shell, a patch, silicone gel fill and are dry heat sterilized.

NATRELLE^TM Cohesive Silicone-Filled Breast Implants (also referred to as Cohesive Round) are available in both smooth and BIOCELL^® textured surfaces.

Cohesive Round Style Number	Breast Implant Description	Size Range
Style 10	Smooth shell surface, moderate projection	120cc - 800cc
Style 15	Smooth shell surface, mid-range projection	155cc - 752cc
Style 20	Smooth shell surface, high projection	120cc - 800cc
Style 40	Smooth shell surface, moderate projection	80cc - 560cc
Style 45	Smooth shell surface, full projection	120cc - 800cc
Style 110	BIOCELL® Textured shell surface, moderate projection	90cc - 510cc
Style 115	BIOCELL® Textured shell surface, mid-range projection	150cc - 716cc
Style 120	BIOCELL® Textured shell surface, high profile	180cc - 650cc

A = width, B = projection

A = Width; B = Projection

Round Breast Implant

NATRELLE^TM Highly Cohesive Silicone-Filled Breast Implants (also referred to as Highly Cohesive Shaped) are manufactured with the BIOCELL^® surface texture.

Highly Cohesive Shaped Style Number	Breast Implant Description	Size Range
410FL	Full height, low projection	140g - 320g
410FM	Full height, moderate projection	155g - 670g
410FF	Full height, full projection	160g - 740g
410FX	Full height, extra full projection	185g - 775g
410ML	Moderate height, low projection	125g - 285g
410MM	Moderate height, moderate projection	160g - 450g
410MF	Moderate height, full projection	140g - 640g
410MX	Moderate height, extra full projection	165g - 685g
410LL	Low height, low projection	135g - 300g
410LM	Low height, moderate projection	140g - 320g
410LF	Low height, full projection	125g - 595g
410LX	Low height, extra full projection	145g - 625g

A = Width; B = Height; C = Projection

Shaped Breast Implant

3. INDICATIONS

• Breast Augmentation - A woman must be at least 22 years old for breast augmentation.
• Breast Reconstruction
• Revision of previous breast augmentation or reconstruction to correct or improve the result of the previous surgery

4. CONTRAINDICATIONS

Patient Groups in which the product is contraindicated:

• Women with existing malignant or pre-malignant tumors of the breast without adequate treatment
• Women with an active infection anywhere in the body
• Women who are currently pregnant or nursing

5. WARNINGS

Surgical Practices in which product use is contraindicated due to potential for compromise of product integrity:

• Alteration: Do not alter the implant.
• Stacking of implants: Do not place more than one implant per breast.
• Reuse: Single use only. Do not resterilize or reuse explanted implants.
• Closed Capsulotomy: Do not treat capsular contracture by forceful external compression, which will likely result in implant damage, rupture, folds and/or hematoma.
• Periumbilical approach: Do not use the periumbilical approach for placement of the implant

AVOID DAMAGE DURING SURGERY

• Care should be taken to avoid the use of excessive force and to minimize handling of the implant during surgical insertion. The unique nature of the highly cohesive gel creates an implant with a precisely defined shape. Excessive force upon insertion of the implant may compromise this shape, potentially leading to an undesirable cosmetic outcome.

  Data accumulated from Allergan's retrieval study analyses of explanted ruptured silicone gel-filled breast implants, observations of surgeries, and a review of the published literature, indicate that forcing an implant through too small an opening or applying concentrated, localized pressure on the implants may result in localized weakening of the breast implant shell potentially leading to shell damage and possible implant rupture.

  An incision should be of appropriate length to accommodate the style, size, and profile of the implant. The incision needed for silicone-filled breast implants will be longer than the one typically made for a saline breast augmentation. The unique nature of the more cohesive gel in the Highly Cohesive breast implant requires an even larger incision to reduce excessive stress on the implant during insertion and minimize the potential for implant damage or deformation (change in shape).

• Care should be taken when using surgical instruments in proximity with the breast implant, including scalpel, sutures, and dissection instrumentation.

  Silicone-filled breast implants are prone to unintended instrument trauma during implantation or during explantation (Brandon et al. 2001, Young and Watson 2001). Shell failure can result from damage by scalpels, suture needles, hypodermic needles, hemostats, and Adson forceps, and has been observed in explanted device shells using scanning electron microscopy (Brandon et al. 2001). Allergan's analyses (retrieval study) of explanted devices have identified unintended surgical instrument damage as one potential cause of shell failure and thus implant rupture.

• Use care in subsequent procedures such as open capsulotomy, breast pocket revision, hematoma/seroma aspiration, and biopsy/lumpectomy to avoid damage to the implant.

  Re-positioning of the implant during subsequent procedures should be carefully evaluated by the medical team and care taken to avoid contamination of the implant. Use of excessive force during any subsequent procedure can contribute to localized weakening of the breast implant shell potentially leading to decreased device performance.

• Do not contact the implant with disposable, capacitor-type cautery devices.
  
  
• Do not alter the implants or attempt to repair or insert a damaged prosthesis.

MICROWAVE DIATHERMY

The use of microwave diathermy in patients with breast implants is not recommended, as it has been reported to cause tissue necrosis, skin erosion, and extrusion of the implant.

6 Precautions

SPECIFIC POPULATIONS

Safety and effectiveness have not been established in patients with the following:

• Autoimmune diseases (for example, lupus and scleroderma).
• A compromised immune system (for example, currently receiving immunosuppressive therapy).
• Conditions or medications that interfere with wound healing and blood clotting.
• Reduced blood supply to breast tissue.
• Radiation to the breast following implantation.
• Clinical diagnosis of depression or other mental health disorders, including body dysmorphic disorder and eating disorders. Patients should be assessed for any history of mental health disorders and should be referred to a mental health professional for further follow up and treatment if necessary. Patients with a diagnosis of depression or other mental health disorder should not undergo surgery until these conditions resolve.

MAMMOGRAPHY

Patient Counseling Information
With breast implants, routine screening mammography will be more difficult. The patient should continue to perform monthly breast examinations for cancer screening; however, this may be more difficult. The implant may interfere with finding breast cancer during mammography. Because the breast and implant is squeezed during mammography, an implant may rupture during the procedure. More x-ray views are necessary for women with breast implants; therefore, a patient will receive more exposure to radiation. However, the benefit of having the mammogram to find cancer outweighs the risk of the additional x-rays.

Patients should be instructed to inform their mammographers about the presence, type and placement of their implants. Patients should be advised to request diagnostic mammography rather than screening mammography.

Presurgical mammography with a follow-up mammogram 6 months to 1 year following surgery may be performed to establish a baseline for future routine mammography.

Orientation Marks
Prior to mammography the radiologist should be alerted to the presence and location of the orientation marks on the Highly Cohesive Shaped implant as these may be visible on the mammographic images. These orientation marks are circular silicone elastomer dots located on the surface of the implant and are used to assist the physician with visual and tactile placement of the implant within the surgical pocket. The posterior surface of most sizes of the Highly Cohesive Shaped implant has 4 orientation marks; the posterior (back) surface of some smaller and/or shorter styles may have only 3 orientation marks. The front (anterior) surface of all Highly Cohesive Shaped implants has 2 orientation marks, as shown below.

RADIATION TO THE BREAST

Allergan has not tested the in-vivo effects of radiation therapy in patients who have breast implants. The literature suggests that radiation therapy does not compromise implant integrity, but may increase the likelihood of capsular contracture, necrosis, and extrusion.

LONG-TERM EFFECTS

Patient Counseling Information
Allergan's ongoing clinical studies of the Cohesive Round implants (the Core Study) and the Highly Cohesive Shaped implants (the pivotal study and Continued Access study) are monitoring the long-term (10 years) safety and effectiveness of these products. In addition, Allergan has initiated a separate large 10-year postapproval study (the Breast Implant Follow-up Study, or BIFS) to address specific issues which the other studies were not designed to fully answer, as well as to provide a real-world assessment of some endpoints. Allergan will update its labeling on a regular basis with the results of these studies.

7 Special Considerations and Risks to be Discussed with the Patient

Patient Counseling Information

The following information should be discussed with patients prior to their decision to proceed with surgery:

• Professional Care - Patients should be advised that follow-up exams as prescribed by their plastic surgeon are recommended to monitor the status of their breast implants.
  
  
• Avoiding Damage during Treatment - Patients should be instructed to inform other treating physicians of the presence of implants to minimize the risk of damage to the implants.
  
  
• Smoking - Patients should be informed that smoking may interfere with the healing process.
  
  
• Breast Examination Techniques - Patients should be instructed to follow the most current medical recommendations regarding breast examination and mammography frequency appropriate for their age and medical history. To maximize the effectiveness of breast self examinations for any palpable lesions, patients should be instructed how to distinguish the implant from breast tissue.

7.1 Complications

Rupture

Patients should be informed that silicone gel-filled breast implants are not lifetime devices and that there is a potential for implant rupture. The decision to remove a ruptured or suspected ruptured implant should be undertaken following review of all available clinical information and after careful consideration between you and your patient. However, if implant rupture is diagnosed, it is recommended that the implant be removed.

Clinical Management of Suspected and Confirmed Rupture

Patients should be informed that following a diagnosis of suspected or confirmed rupture that implant removal might be recommended by their surgeon, particularly in those instances where there may be evidence that silicone gel has moved beyond the confines of the fibrous capsule that typically forms around the device. Most surgeons in Allergan's clinical studies have chosen to remove implants suspected of rupture.

Patients should be aware that, rarely, an intracapsular rupture may progress to an extracapsular rupture. Studies of Danish women indicate that over a 2-year period, about 10% of the implants with intra-capsular rupture progressed to extracapsular rupture as detected by MRI, i.e. for women with silicone gel rupture within the scar tissue capsule detected via MRI after 2 years, 1 in 10 of these women will have progression of the gel outside the scar tissue capsule. In about half of these cases of progression from intra- to extra-capsular rupture, the women had experienced trauma or mammography. In the other half, no cause was given.

In the women with extracapsular rupture, after 2 years, the amount of silicone seepage outside the scar tissue capsule increased for about 14% of these women, i.e. for 100 women with silicone gel rupture outside the scar tissue capsule, the amount of gel outside the scar tissue capsule increased for 14 women 2 years later. This type of information is not available for Allergan-specific implants and it pertains to a variety of silicone implants from a variety of manufacturers and implant models. Given the greater cohesivity of Highly Cohesive implants, it is likely that they have less risk of extracapsular rupture than other silicone implants.

Monitoring for Implant Rupture

Patients should be informed that periodic evaluation of the integrity of their breast implants is required to determine whether the implant has ruptured in the absence of any clinical symptoms. While there are various diagnostic methods available to evaluate for possible implant rupture including physical examination, mammogram, and ultrasound, FDA believes the best method for detection of rupture is Magnetic Resonance Imaging (MRI). In most cases, an MRI diagnosis of rupture or possible rupture is consistent with a ruptured implant at explantation (Brown et al. 2000, Holmich et al. 2004). However, the scientific value of MRI is still developing. Allergan's clinical study results and other published reports have found that in some cases MRI may falsely show a breast implant rupture when there is none (false positive). In some cases MRI may also show no breast implant rupture when there is one (false negative). Scaranelo et al. (2004) found that the sensitivity and specificity of MRI to detect rupture in asymptomatic patients was 64% and 77%, respectively. Thus, MRI findings of rupture should not be considered definitive (Scaranelo et al. 2004).

Health Canada and the Canadian Expert Advisory Panel on silicone gel-filled breast implants advocate the following approach to monitor patients with breast implants. In consideration of all the available scientific information, it has been suggested that the process for determining implant integrity (e.g. rupture) should be related to clinical signs and symptoms. Thus, the following 6-step process is recommended for screening for silicone gel-filled breast implant rupture:

1. Patient self-examination;
   
   
2. New symptom or sign suspected;
   
   
3. Physician physical examination, related to a periodic review or new symptoms and signs, suggests findings that warrant further investigation;
   
   
4. Ultrasound, mammogram, or both of the implant and the breast involved should be acquired;
   
   
5. MRI if ultrasound is negative or inconclusive. The MRI should be performed at a centre with a breast coil with a magnet of at least 1.5 Tesla. The MRI should be read by a radiologist who is familiar with looking for implant rupture; and
   
   
6. If signs of rupture are seen on MRI, then in consultation with the plastic surgeon, the implant(s) may be removed, with or without replacement.

Rupture Rate Information on Allergan Implants

Cohesive Round Breast Implants
In Allergan's Core Study, rupture was assessed for patients who had scheduled MRIs to screen for silent rupture (i.e., part of the MRI cohort) and those who were not assessed for rupture by MRI (i.e., part of the non-MRI cohort). The rupture rates in the MRI cohorts were 8.6% for primary augmentation, 0% for revision-augmentation, 11.4% for primary reconstruction, and 0% for revision-reconstruction. The rupture rate for the whole MRI cohort in the Core Study through 7 years was 7.3% for patients and 4.5% for implants. Across all patients in the Core Study, all ruptures were intracapsular gel, but one rupture progressed to extracapsular gel following exploratory surgery to confirm the rupture and then implant replacement was delayed. There were no cases of migrated gel.

Further rupture rate information on Cohesive Round implants is provided from a published European study known as the International MRI Study. Silent rupture data were collected via a single MRI on 77 augmentation, 11 reconstruction, and 18 revision patients implanted with smooth and textured NATRELLE^TM implants by surgeons in 5 countries. The average age of the implants was approximately 11 years. Silent rupture was found in approximately 15% of the combined group of augmentation, reconstruction, and revision patients and 8% of the implants. There was one possible case of extracapsular rupture with the remainder classified as intracapsular ruptures. No cases of migrated gel were found.

Highly Cohesive Shaped Breast Implants
In Allergan's pivotal study, rupture was assessed for patients who had scheduled MRIs to screen for silent rupture (i.e., part of the MRI cohort) and those who were not assessed for rupture by MRI (i.e., part of the non-MRI cohort). The rupture rates in the MRI cohorts were 4.3% for primary augmentation, 5.0% for revision-augmentation, 7.2% for primary reconstruction, and 9.5% for revision-reconstruction. The rupture rate for the whole MRI cohort in the pivotal study through 5 years was 5.5% for patients and 3.2% for implants. Across all patients in the pivotal study, all of the ruptures were intracapsular, with no cases of extracapsular rupture or migrated gel.

Further rupture information on Highly Cohesive Shaped implants is provided from a published study known as the 410 Swedish MRI Study. Silent rupture data were collected via a single MRI on 124 augmentation and 20 revision patients implanted with NATRELLE^TM Highly Cohesive implants at one hospital. The average age of the implants was approximately 6 years. Silent rupture was found in approximately 2% of the combined group of augmentation and revision patients and 1% of the implants. All ruptures were classified as intracapsular with no cases of extracapsular rupture or migrated gel.

Reoperation (Additional Surgeries)

Patients should be advised that additional surgery to their breast and/or implant may be necessary over the course of their lives.

Capsular Contracture

Patients should be advised that capsular contracture may be more common following infection, hematoma, and seroma, and the chance of it happening may increase over time. Capsular contracture occurs more commonly in revision patients than in primary augmentation or reconstruction patients. Capsular contracture is also a risk factor for implant rupture, and it is one of the most common reasons for reoperation.

Explantation (Implant Removal)

Patients should be advised that implants are not considered lifetime devices, and they will potentially undergo implant removal, with or without replacement, over the course of their lives. Patients should also be advised that the changes to their breast following explantation are irreversible.

Infection

In rare instances, acute infection may occur in a breast with implants. The signs of acute infection include erythema, tenderness, fluid accumulation, pain and fever. Very rarely, Toxic Shock Syndrome, a potentially life-threatening condition, has been reported in women after breast implant surgery. It is characterized by symptoms that occur suddenly and include high fever (102°F, 38.8°C or higher), vomiting, diarrhea, a sunburn-like rash, red eyes, dizziness, lightheadedness, muscle aches, and drops in blood pressure, which may cause fainting. Patients should be advised to contact a physician immediately for diagnosis and treatment for any of these symptoms.

Cosmetic Dissatisfaction (Unsatisfactory Results)

Patients should be informed that dissatisfaction with cosmetic results related to such things as scar deformity, hypertrophic scarring, capsular contracture, asymmetry, displacement, incorrect size, unanticipated contour, and palpability may occur. Careful surgical planning and technique can minimize, but not preclude, the risk of such results. Pre-existing asymmetry may not be entirely correctable. Physiological and behavioral differences among patients and variations in surgical techniques and medical treatments account for a wide variety of responses to silicone gel-filled breast implant surgery. Revision surgery may be indicated to maintain patient satisfaction but carries additional considerations and risks.

Breastfeeding

Difficulties have been reported following breast surgery, including breast reduction and breast augmentation. A periareolar surgical approach may further increase the chance of breastfeeding difficulties.

Additional Complications

After breast implant surgery the following may occur and/or persist, with varying intensity and/or for a varying length of time: pain, hematoma/seroma, changes in nipple and breast sensation, extrusion, necrosis, delayed wound healing, and breast tissue atrophy/chest wall deformity. Calcium deposits can form in the tissue capsule surrounding the implant with symptoms that may include pain and firmness. Lymphadenopathy has also been reported in some women with implants.

7.2 Other Reported Conditions

Patient Counseling Information
There have been reports of other conditions in women with breast implants. Many of these conditions have been studied to evaluate their potential association with breast implants. No cause-and-effect relationship has been established between breast implants and the conditions listed below. There is the possibility of risks, yet unknown, which in the future could be determined to be associated with breast implants.

Connective Tissue Disease

Connective tissue diseases include diseases such as lupus, scleroderma, and rheumatoid arthritis. There have been a number of published epidemiological studies which have looked at whether having a breast implant is associated with having a typical or defined connective tissue disease. The most recent of these concluded that the weight of the evidence did not support causal association between implants and definite or atypical CTD. The study size needed to conclusively rule out a smaller risk of connective tissue disease (≤2) would need to be very large. Published studies taken together show that breast implants are not significantly associated with a risk of developing a specific connective tissue disease. These studies do not distinguish between women with intact and ruptured implants. Only one study evaluated specific CTD diagnoses and symptoms in women with silent ruptured versus intact implants, but the study was too small to rule out a small risk.

Cancer

Breast Cancer - Reports in the medical literature indicate that patients with breast implants are not at a greater risk than those without breast implants for developing breast cancer. Some reports have suggested that breast implants may interfere with or delay breast cancer detection by mammography and/or biopsy; however, other reports in the published medical literature indicate that breast implants neither significantly delay breast cancer detection nor adversely affect survival of women with breast cancer.

Brain cancer - One recent study has reported an increased incidence of brain cancer in women with breast implants as compared to the general population. The incidence of brain cancer, however, was not significantly increased in women with breast implants when compared to women who had other plastic surgeries. Another recently published review of four large studies in women with cosmetic implants concluded that the evidence does not support an association between brain cancer and breast implants. A recent epidemiological review also lent support to the lack of causation between implants and any type of cancer.

Respiratory/lung cancer - One study has reported an increased incidence of respiratory/lung cancer in women with breast implants. Other studies of women in Sweden and Denmark have found that women who get breast implants are more likely to be current smokers than women who get breast reduction surgery or other types of cosmetic surgery.

Cervical/vulvar cancer - One study has reported an increased incidence of cervical/vulvar cancer in women with breast implants. The cause of this increase is unknown.

Other cancers - One study has reported an increased incidence of stomach cancer and leukemia in women with breast implants compared to the general population. This increase was not significant when compared to women who had other types of plastic surgeries.

Neurological

Some women with breast implants have complained of neurological symptoms (such as difficulties with vision, sensation, muscle strength, walking, balance, thinking or remembering things) or diseases (such as multiple sclerosis), which they believe are related to their implants. A scientific expert panel report found that the evidence for a neurological disease or syndrome caused by or associated with breast implants is insufficient or flawed. Further review of the epidemiologic evidence also failed to find an association between implants and neurologic disease.

Mental Health Disorders

Patients should be encouraged to discuss any history of mental health disorders, including a clinical diagnosis of depression, body dysmorphic disorder or eating disorder with you during their consultation visit(s). Patients with a diagnosis of depression or other mental health disorder should be encouraged to wait to schedule surgery until these conditions resolve.

Suicide

In several studies, a higher incidence of suicide was observed in women with breast implants. The reason for the observed increase is unknown, but it was found that women with breast implants had higher rates of hospital admission due to psychiatric causes prior to surgery, as compared with women who had breast reduction or in the general population of Danish women.

Effects on Children

At this time, it is not known if a small amount of silicone may pass through from the breast implant silicone shell into breast milk during breastfeeding. Although there are no current established methods for accurately detecting silicone levels in breast milk, a study measuring silicon (one component in silicone) levels did not indicate higher levels in breast milk from women with silicone gel-filled implants when compared to women without implants.

In addition, concerns have been raised regarding potential damaging effects on children born to mothers with implants. Two studies in humans have found that the risk of birth defects overall is not increased in children born after breast implant surgery. Although low birth weight was reported in a third study, other factors (for example, lower pre-pregnancy weight) may explain this finding. One of the authors of these human studies recommended further research on infant health. A review of the evidence did not find that offspring of women with implants were at an increased risk for esophageal disorders, rheumatic diseases, or congenital malformations.

Gel Diffusion and Potential Health Consequences

Small quantities of low molecular weight (LMW) siloxane compounds and platinum (in a zero valance/biocompatible state), have been found to diffuse (leak) through an intact implant shell. Studies on implants implanted for a long duration have suggested that such diffusion may be a contributing factor in the development of capsular contracture and lymphadenopathy. Other studies have shown evidence of silicone in scar tissue capsules surrounding the implant, in axillary lymph nodes, and in distant organs, which may be due to gel diffusion. The clinical significance of the presence of silicone in these tissues is unknown. Other studies have reported that certain silicones (for example, D4 and D5) and platinum leak from intact breast implants and are present in surrounding tissue. The clinical significance to humans of the presence of silicone in the body tissues is unknown. However, there has been no evidence in the medical literature or from Allergan's own testing associating gel diffusion with local complications in breast implant patients. Studies have demonstrated that the low concentration of platinum contained in breast implants is in the zero valence or most biocompatible state.

Delayed-type Hypersensitivity

While there is no scientific evidence that silicone can cause hypersensitivity reactions in humans, some animal testing reports in the literature suggest evidence of a delayed-type hypersensitivity to silicone. The biological mechanism and outcome for these findings in animal models remain unknown.

8 Preclinical Study Information

Preclinical study of the silicone-filled breast implants revealed that the materials of which the devices are made are biocompatible, the silicone elastomer shell is durable, and there is a low potential for gel diffusion (bleed). A summary of the preclinical studies conducted by Allergan, including chemistry, toxicology, and physical/mechanical testing can be found in the Summary Basis for Decision (SBD) document on Health Canada's website at www.hc-sc.gc.ca.

9 Allergan Clinical Studies

9.1 Overview of Allergan's Core Study (Cohesive Round Implants)

The Core Study is a 10-year study to assess safety and effectiveness in augmentation, reconstruction, and revision (revision-augmentation and revision-reconstruction) patients implanted with Cohesive Round breast implants. Patient follow-up is at 0-4 weeks, 6 months, 12 months, 24 months, and annually through 10 years. Safety is assessed by complications, such as implant rupture, capsular contracture, and reoperation. Benefit (effectiveness) is assessed by breast size change, patient satisfaction, and measures of body image/esteem and self esteem.

The Core Study consists of 715 patients. This includes 455 augmentation patients, 147 revision-augmentation patients, 98 reconstruction patients, and 15 revision-reconstruction patients. The study is currently ongoing, with the results through 7 years reported in this brochure. Allergan will periodically update this brochure as more information becomes available.

9.1.1 Augmentation and Revision-Augmentation Patients

Described below are the benefits and complications reported in the Allergan Core Study for augmentation and revision-augmentation patients.

Allergan's results indicate that the risk of any complication at some point through 7 years after implant surgery is 45% for primary augmentation patients and 57% for revision-augmentation patients. However, the majority of women were satisfied with their implants. The results also indicate that the chance of additional surgery (reoperation) through the first 7 years is about 1 in 3 for primary augmentation patients (with capsule procedures as the most common type of additional surgery), and more than 1 in 3 for revision-augmentation patients (with the most common type of additional surgery being capsule procedures). The information below provides more details about the complications and benefits of Cohesive Round breast implants.

Patient Accounting (Follow-Up Rates)

The Core Study enrolled 455 augmentation patients. Of the women expected to be seen at the 7-year follow-up visit, 74% were seen.

The Core Study enrolled 147 revision-augmentation patients. Of the women expected to be seen at the 7-year follow-up visit, 72% were seen.

Effectiveness Outcomes

The benefits of Cohesive Round breast implants were assessed by a variety of outcomes, including bra cup size change and assessments of patient satisfaction, body image, body esteem, and self concept. Data were collected before implantation and at scheduled follow-up visits.

Primary Augmentation Patients:
For primary augmentation patients, 396 of the original 455 patients had a breast measurement within 18 months of surgery. Of these 396 patients, 41% increased by 1 cup size; 45% increased by 2 cup sizes; 8% increased by more than 2 cup sizes; and 6% had no increase or decreased.

Allergan patient satisfaction was based on a 5-point scale assessment of satisfaction with their implants at the time of the follow-up visits. 317 (70%) of the original 455 patients provided a satisfaction rating at 7 years after implantation with 95% of these patients indicating that they were satisfied with their breast implants.

Quality of life assessments were made at 1, 2, 4, and 6 years post-implant. Therefore, 6 year data is provided herein. For primary augmentation patients, the SF-36, which measures mental and physical health, showed a slight improvement in one scale and a slight worsening in some of the other scales after 6 years compared to before breast implantation, although all scales remained higher than the general U.S. female population. For patient responses to questions regarding overall self-concept/self-esteem, there was a decrease in self-concept on the Tennessee Self Concept Scale and no change in overall self esteem on the Rosenberg Self Esteem Scale 6 years after receiving implants. Patient responses to questions on the Body Esteem Scale regarding overall self esteem related specifically to one's body did not show a change 6 years after receiving implants, but a decrease in weight concern and physical condition, and increase with regard to sexual attractiveness were shown. On the Rowland Expectation Scale, patients showed significant improvement in self image, social relations, and daily living. Breast satisfaction was significantly increased after 6 years, including satisfaction with breast shape, size, feel or touch, and how well they matched.

Revision-Augmentation Patients:
Revision-augmentation patients did not undergo a measurement of bra cup size change because they were undergoing replacement of an existing breast implant.

Patient satisfaction was based on a 5-point scale assessment of satisfaction with their implants at the time of the follow-up visits. 91 (62%) of the original 147 revision-augmentation patients provided a satisfaction rating at 7 years. Of these 91 patients, 89% indicated that they were satisfied with their breast implants.

For revision-augmentation patients, the SF-36, which measures mental and physical health, showed no significant changes in all but one of these scales after 6 years. Patient responses to questions on the Tennessee Self Concept Scale and Rosenberg Self Esteem Scale regarding overall self-concept/self-esteem showed no changes 6 years after receiving implants. Patient responses to questions on the Body Esteem Scale regarding overall body image showed no changes, but a decrease with regard to physical condition was shown. On the Rowland Expectation Scale, patients showed significant improvement in self image, social relations, and daily living. Breast satisfaction was significantly increased after 6 years, including satisfaction with breast shape, size, feel or touch, and how well they matched.

Safety Outcomes

Table 1 describes the complications experienced by primary augmentation and revision-augmentation patients in the Core Study.

Table 1
Core Study: Complications
7-Year Cumulative First Occurrence Kaplan-Meier Risk Rates, By Patient

Complication*	Primary Augmentation N = 455 Rate (%) (95% CI)	Revision-Augmentation N = 147 Rate (%) (95% CI)
Reoperation	30.1% (26.0%, 34.7%)	40.5% (32.8%, 49.3%)
Capsular Contracture	15.5% (12.3%, 19.3%)	20.4% (14.4%, 28.4%)
Breast Pain	11.4% (8.6%, 14.8%)	10.6% (6.4%, 17.4%)
Implant Removal with Replacement	11.0% (8.4%, 14.4%)	20.9% (14.8%, 29.0%)
Swelling	9.2% (6.8%, 12.3%)	8.4% (4.7%, 14.8%)
Implant Rupture (MRI cohort)	8.6% (5.0%, 14.7%)	0% N/A
Nipple Complications	6.7% (4.7%, 9.5%)	<1% N/A
Implant Malposition	5.2% (3.5%, 7.7%)	6.1% (3.1%, 11.9%)
Scarring/Hypertrophic Scarring	3.7% (2.3%, 6.0%)	6.0% (3.0%, 11.6%)
Asymmetry	3.3% (1.9%, 5.5%)	3.7% (1.5%, 8.6%)
Implant Removal without Replacement	3.1% (1.8%, 5.5%)	4.3% (1.8%, 10.1%)
Ptosis	2.2% (1.2%, 4.2%)	4.8% (2.2%, 10.5%)
Breast/Skin Sensation Changes	1.6% (0.8%, 3.3%)	2.2% (0.7%, 6.8%)
Hematoma	1.6% (0.7%, 3.2%)	2.1% (0.7%, 6.3%)
Implant Palpability/Visibility	1.6% (0.8%, 3.4%)	6.8% (3.6%, 12.6%)
Seroma/Fluid Accumulation	1.6% (0.7%, 3.2%)	6.1% (3.1%, 12.0%)
Wrinkling/Rippling	1.2% (0.5%, 2.9%)	4.6% (2.1%, 10.0%)
Delayed Wound Healing	1.1% (0.5%, 2.7%)	<1% N/A
Bruising	<1% N/A	3.0% (1.1%, 7.9%)
Infection	<1% N/A	1.4% (0.4%, 5.5%)
Capsule Calcification, Gel Migration, Implant Extrusion, Irritation, Lymphadenopathy, Lymphedema, Other Complications, Pneumothorax, Redness, Skin Rash, Tissue/Skin Necrosis	0% - <1% N/A	0% - <1% N/A

^* Most events were assessed with severity ratings, and the rates shown in the table include only complications rated moderate, severe or very severe (excludes mild and very mild ratings). All occurrences of reoperation, implant removal, implant rupture, implant extrusion and pneumothorax are included.

Reasons for Reoperation

Table 2 provides the main reason for each reoperation performed through 7 years in primary augmentation and revision-augmentation patients.

Table 2
Core Study: Main Reason for Reoperation through 7 Years

Reason for Reoperation	Primary Augmentation n (% of 177 reoperations)	Revision-Augmentation n (% of 97 reoperations)
Capsular Contracture	47 (26.6%)	20 (20.6%)
Implant Malposition	24 (13.6%)	11 (11.3%)
Ptosis	21 (11.9%)	9 (9.3%)
Need for Biopsy	19 (10.7%)	8 (8.2%)
Suspected Rupture	13 (7.3%)	5 (5.2%)
Hematoma/Seroma	12 (6.8%)	13 (13.4%)
Patient Request for Style/Size Change	9 (5.1%)	3 (3.1%)
Scarring/Hypertrophic Scarring	8 (4.5%)	7 (7.2%)
Asymmetry	6 (3.4%)	3 (3.1%)
Breast Cancer Mass	3 (1.7%)	3 (3.1%)
Breast Pain	3 (1.7%)	1 (1.1%)
Delayed Wound Healing	3 (1.7%)	2 (2.1%)
Implant Palpability/Visibility	2 (1.1%)	1 (1.0%)
Infection	2 (1.1%)	3 (3.1%)
Wrinkling/Rippling	2 (1.1%)	2 (2.1%)
Implant Extrusion	1 (0.6%)	1 (1.0%)
Necrosis	1 (0.6%)	0
Nipple Complications	1 (0.6%)	3 (3.1%)
Breast Tissue Contour Deformity, Device Injury	0	1 each (1.0%)
Total	177 (100%)	97 (100%)

Reasons for Implant Removal

The main reasons for implant removal among primary augmentation and revision-augmentation patients over the 7 years are shown in Table 3.

Table 3
Core Study: Main Reason for Implant Removal through 7 Years

Reason for Removal	Primary Augmentation n (% of 107 Explants)	Revision-Augmentation n (% of 59 Explants)
Capsular Contracture	35 (32.7%)	18 (30.5%)
Patient Request for Style/Size Change	22 (20.6%)	10 (17.0%)
Implant Malposition	11 (10.3%)	10 (17.0%)
Suspected Rupture	11 (10.3%)	4 (6.8%)
Asymmetry	8 (7.5%)	1 (1.7%)
Ptosis	5 (4.7%)	6 (10.2%)
Breast Pain	4 (3.7%)	1 (1.7%)
Wrinkling/Rippling	4 (3.7%)	2 (3.4%)
Breast Cancer Mass	2 (1.9%)	2 (3.4%)
Infection	2 (1.9%)	2 (3.4%)
Breast Tissue Contour Deformity, Implant Extrusion, Need for Biopsy	1 each (0.9%)	0
Scarring/Hypertrophic Scarring	0	3 (5.1%)
Total	107 (100%)	59 (100%)

Other Events

Through 7 years, events other than the complications described in the previous tables were collected in the Core Study for augmentation and revision-augmentation patients. Some of these events, such as breast cancer and CTD, can occur in non-implanted patients. Therefore, without a comparison group of women with similar characteristics (such as age, race, etc.) and without breast implants, no conclusions can be made about the relationship between breast implants and some of these other events.

Benign breast disease occurred in 13% of primary augmentation and in 15% of revision-augmentation patients. Malignant breast disease occurred in 1% of primary and 1% of revision-augmentation patients. CTD events were less than 1%.

9.1.2 Reconstruction and Revision-Reconstruction Patients

Described below are the benefits and complications reported in the Core Study for reconstruction and revision-reconstruction patients.

Allergan's results indicate that the risk of any complication at some point through 7 years after implant surgery is 70% for primary reconstruction patients and 73% for revision-reconstruction patients. However, the majority of women were satisfied with their implants. The results also indicate that the chance of additional surgery (reoperation) through the first 7 years is 1 in 2 for primary reconstruction patients (with implant removal and replacement as the most common type of additional surgery), and 1 in 3 for revision-reconstruction patients (with nipple reconstruction/tattoo as the most common type of additional surgery). The information below provides more details about the complications and benefits of Cohesive Round breast implants.

Patient Accounting (Follow-Up Rates)

The Core Study enrolled 98 reconstruction patients. Of the women expected to be seen at the 7-year follow-up visit, 87% were seen.

The Core Study enrolled 15 revision-reconstruction patients. Of the women expected to be seen at the 7-year follow-up visit, 83% were seen.

Effectiveness Outcomes

The benefits of Cohesive Round breast implants were assessed by a variety of outcomes, including assessments of patient satisfaction, body image, body esteem, and self concept. Data were collected before implantation and at scheduled follow-up visits.

Primary Reconstruction Patients:
Patient satisfaction was based on a 5-point scale assessment of satisfaction with their implants at the time of the follow-up visits. 63 (64%) of the original 98 patients provided a satisfaction rating at 7 years after implantation with 90% of these patients indicating that they were satisfied with their breast implants.

Quality of life assessments were made at 1, 2, 4, and 6 years post-implant. Therefore, 6 year data is provided herein. For primary reconstruction patients, the SF-36, which measures mental and physical health, showed no changes after 6 years compared to before breast implantation. For patient responses to questions regarding overall self-concept/self-esteem, there was no change in self-concept on the Tennessee Self Concept Scale and no change in overall self esteem on the Rosenberg Self Esteem Scale 6 years after receiving implants. Patient responses to questions on the Body Esteem Scale regarding overall self esteem related specifically to one's body also did not show a change 6 years after receiving implants. On the Rowland Expectation Scale, patients showed significant improvement in self image, social relations, and well being. Breast satisfaction was significantly increased after 6 years, including satisfaction with breast shape, size, feel or touch, and how well they matched.

Revision-Reconstruction Patients:
Patient satisfaction was based on a 5-point scale assessment of satisfaction with their implants at the time of the follow-up visits. 10 (67%) of the original 15 revision-reconstruction patients provided a satisfaction rating at 7 years. Of these 10 patients, 90% indicated that they were satisfied with their breast implants.

For revision-reconstruction patients, responses were similar pre- and post-implantation on the SF-36, Tennessee Self Concept Scale, Rosenberg Self Esteem Scale and Body Esteem Scale. On the Rowland Expectation Scale, patients showed significant improvement in self image, social relations, and daily living. Breast satisfaction was significantly increased after 6 years, including satisfaction with breast shape, size, feel or touch, and how well they matched.

Safety Outcomes

Table 4 describes the complications experienced by primary reconstruction and revision-reconstruction patients in the Core Study.

Table 4
Core Study: Complications
7-Year Cumulative First Occurrence Kaplan-Meier Risk Rates, By Patient

Complication*	Primary Reconstruction N = 98 Rate (%) (95% CI)	Revision-Reconstruction N = 15 Rate (%)** (95% CI)
Reoperation	53.3% (43.3%, 63.9%)	40.0% (16.3%, 67.7%)
Implant Removal with Replacement	23.7% (16.1%, 34.2%)	6.7% (0.2%, 31.9%)
Asymmetry	22.8% (15.3%, 33.3%)	13.3% (1.7%, 40.5%)
Capsular Contracture	17.1% (10.6%, 26.8%)	6.7% (0.2%, 31.9%)
Implant Rupture (MRI cohort)	11.4% (4.9%, 25.3%)	0% N/A***
Wrinkling/Rippling	9.1% (4.4%, 18.4%)	6.7% (0.2%, 31.9%)
Implant Removal without Replacement	7.7% (3.5%, 16.4%)	0% N/A
Swelling	7.1% (3.5%, 14.4%)	0% N/A
Breast Pain	4.8% (1.8%, 12.6%)	6.7% (0.2%, 31.9%)
Scarring/Hypertrophic Scarring	4.5% (1.7%, 11.5%)	0% N/A
Implant Palpability/Visibility	4.1% (1.3%, 12.1%)	6.7% (0.2%, 31.9%)
Implant Malposition	3.9% (1.3%, 11.9%)	13.3% (1.7%, 40.5%)
Nipple Complications	3.3% (1.1%, 9.8%)	0% N/A
Infection	3.2% (1.0%, 9.5%)	0% N/A
Tissue/Skin Necrosis	2.3% (0.6%, 8.8%)	0% N/A
Redness	2.1% (0.5%, 8.3%)	0% N/A
Skin Rash	2.0% (0.5%, 7.9%)	6.7% (0.2%, 31.9%)
Hematoma	1.5% (0.2%, 10.4%)	0% N/A
Bruising	1.0% (0.1%, 7.1%)	6.7% (0.2%, 31.9%)
Delayed Wound Healing, Implant Extrusion, Other Complications	1.0% each (0.1%, 7.2%)	0% N/A
Lymphedema, Seroma/Fluid Accumulation	0% N/A	6.7% each (0.2%, 31.9%)
Breast/Skin Sensation Changes, Capsule Calcification, Gel Migration, Irritation, Lymphadenopathy, Pneumothorax, Ptosis	0% N/A	0% N/A

^* Most events were assessed with severity ratings, and the rates shown in the table include only complications rated moderate, severe or very severe (excludes mild and very mild ratings). All occurrences of reoperation, implant removal, implant rupture, implant extrusion and pneumothorax are included.
^** Calculated as a percentage of enrolled with binomial confidence interval.
^*** No ruptures were reported in the MRI (n=5) or non-MRI (n=10) cohorts.

Reasons for Reoperation

Table 5 provides the main reason for each reoperation performed through 7 years in primary reconstruction and revision-reconstruction patients.

Table 5
Core Study: Main Reason for Reoperation through 7 Years

Reason for Reoperation	Primary Reconstruction n (% of 73 reoperations)	Revision-Reconstruction n (% of 9 reoperations)
Implant Malposition	14 (19.2%)	0
Asymmetry	12 (16.4%)	1 (11.1%)
Capsular Contracture	10 (13.7%)	1 (11.1%)
Need for Biopsy	8 (11.0%)	0
Hematoma/Seroma	6 (8.2%)	0
Ptosis	4 (5.5%)	1 (11.1%)
Patient Request for Style/Size Change	3 (4.1%)	0
Scarring/Hypertrophic Scarring	3 (4.1%)	1 (11.1%)
Suspected Rupture	3 (4.1%)	0
Breast Cancer Mass, Breast Tissue Contour Deformity, Implant Extrusion	2 each (2.7%)	0
Nipple Complications	1 (1.4%)	5 (55.6%)
Delayed Wound Healing, Necrosis, Wrinkling/Rippling	1 each (1.4%)	0
Total	73 (100%)	9 (100%)

Reasons for Implant Removal

The main reasons for implant removal among primary reconstruction and revision-reconstruction patients over the 7 years are shown in Table 6.

Table 6
Core Study: Main Reason for Implant Removal through 7 Years

Reason for Removal	Primary Reconstruction n (% of 34 explants)	Revision-Reconstruction n (% of 1 explant)
Implant Malposition	9 (26.5%)	0
Asymmetry	7 (20.6%)	1 (100%)
Capsular Contracture	7 (20.6%)	0
Patient Request for Style/Size Change	4 (11.8%)	0
Suspected Rupture	3 (8.8%)	0
Hematoma/Seroma, Implant Extrusion, Necrosis, Wrinkling/Rippling	1 each (2.9%)	0
Total	34 (100%)	1 (100%)

Other Events

Through 7 years, events other than the complications described in the previous tables were collected in the Core Study for reconstruction and revision-reconstruction patients. Some of these events, such as breast cancer and CTD, can occur in non-implanted patients. Therefore, without a comparison group of women with similar characteristics (such as age, race, etc.) and without breast implants, no conclusions can be made about the relationship between breast implants and some of these other events.

Benign breast disease occurred in 17% of primary reconstruction patients and in 7% of revision-reconstruction patients. Malignant breast cancer was detected in 10% of primary reconstruction patients with none detected in revision-reconstruction patients. A 2% CTD rate (rheumatoid arthritis and undifferentiated CTD) occurred in primary reconstruction patients with no CTDs detected in revision-reconstruction patients.

9.2 Overview of Allergan's Pivotal Study (Highly Cohesive Shaped Implants)

The pivotal study is a 10-year study to assess safety and effectiveness in augmentation, reconstruction, and revision (revision-augmentation and revision-reconstruction) patients implanted with Highly Cohesive Shaped implants. Patient follow-up is at 0-4 weeks, 6 months, 12 months, 24 months, and annually through 10 years. Safety is assessed by complications, such as implant rupture, capsular contracture, and reoperation. Benefit (effectiveness) is assessed by breast size change, patient satisfaction and measures of body image/esteem and self esteem.

The pivotal study consists of 941 patients. This includes 492 augmentation patients, 156 revision-augmentation patients, 225 reconstruction patients, and 68 revision-reconstruction patients. The study is currently ongoing, with the results through 5 years reported in this brochure. Allergan will periodically update this brochure as more information becomes available.

9.2.1 Augmentation and Revision-Augmentation Patients

Described below are the benefits and complications reported in the pivotal study for augmentation and revision-augmentation patients.

Allergan's results indicate that the risk of any complication at some point through 5 years after implant surgery is 25% for primary augmentation patients and 39% for revision-augmentation patients. However, the majority of women were satisfied with their implants. The results also indicate that the chance of additional surgery (reoperation) through the first 5 years is approximately 1 in 6 for primary augmentation patients (with implant removal and replacement as the most common type of additional surgery), and almost 1 in 3 for revision-augmentation patients (with implant removal and replacement as the most common type of additional surgery). The information below provides more details about the complications and benefits of Highly Cohesive Shaped implants.

Patient Accounting (Follow-Up Rates)

The pivotal study enrolled 492 augmentation patients. Of the women expected to be seen at the 5-year follow-up visit, 81% were seen.

The pivotal study enrolled 156 revision-augmentation patients. Of the women expected to be seen at the 5-year follow-up visit, 80% were seen.

Effectiveness Outcomes

The benefits of Highly Cohesive Shaped breast implants were assessed by a variety of outcomes, including bra cup size change and assessments of patient satisfaction, body image, body esteem, and self concept. Data were collected before implantation and at scheduled follow-up visits for those patients who still had their original implants and who came back for these visits. Quality of life data were collected through the first 2 years after implantation.

Primary Augmentation Patients:
Of the 466 patients with both a valid pre- and post-implant bra size, the majority of patients increased the size of their breasts by either 1 cup size (38%) or 2 cup sizes (53%). The remaining patients increased by more than 2 cup sizes (6%) or maintained the same cup size (3%).

Patient satisfaction was based on a 5-point scale assessment of satisfaction with their implants at the time of the follow-up visits. 386 (78%) of the original 492 patients provided a satisfaction rating at 5 years after implantation with 97% of these patients indicating that they were satisfied with their breast implants.

For primary augmentation patients, the SF-36, which measures mental and physical health, showed no significant changes after 2 years compared to before breast implantation, and all scales remained higher than the general U.S. female population. For patient responses to questions regarding overall self-concept/self-esteem, there was no change in self-concept on the Tennessee Self Concept Scale and no change in overall self esteem on the Rosenberg Self Esteem Scale 2 years after receiving implants. Patient responses to questions on the Body Esteem Scale regarding overall body image did not show a change 2 years after receiving implants, but body esteem related to sexual attractiveness did show an increase. On the Rowland Expectation Scale patients showed significant improvement in self image, social relations and daily living. Breast satisfaction was significantly increased after 2 years, including satisfaction with breast shape, size, feel or touch, and how well they matched.

Revision-Augmentation Patients:
Patient satisfaction was based on a 5-point assessment of satisfaction with their implants at the time of the follow-up visits. 114 (73%) of the original 156 revision-augmentation patients provided a satisfaction rating at 5 years. Of these 114 patients, 94% indicated that they were satisfied with their breast implants.

Effectiveness measures such as the SF-36 assess the effect of implantation on quality of life, which is not feasible for revision-augmentation patients with pre-existing implants prior to enrollment in the study. Therefore, these assessments were not performed for revision-augmentation patients.

Safety Outcomes

Table 7 describes the complications experienced by primary augmentation and revision-augmentation patients in the pivotal study.

Table 7
Pivotal Study: Complications
5-Year Cumulative First Occurrence Kaplan-Meier Risk Rates, By Patient

Complication*	Primary Augmentation N = 492 Rate (%) (95% CI)	Revision-Augmentation N = 156 Rate (%) (95% CI)
Reoperation	16.7% (13.6%, 20.4%)	30.3% (23.6%, 38.5%)
Implant Removal with Replacement	7.6% (5.5%, 10.4%)	16.1% (10.9%, 23.2%)
Capsular Contracture	3.3% (2.0%, 5.5%)	6.9% (3.8%, 12.5%)
Implant Malposition	2.3% (1.3%, 4.2%)	6.1% (3.2%, 11.3%)
Implant Rupture (MRI Cohort)	4.3% (1.9%, 9.3%)	5.0% (1.3%, 18.4%)
Breast Pain	2.2% (1.2%, 4.0%)	2.1% (0.7%, 6.3%)
Swelling	2.1% (1.1%, 3.9%)	2.8% (1.0%, 7.2%)
Infection	1.7% (0.9%, 3.4%)	2.1% (0.7%, 6.3%)
Other Complications	1.4% (0.6%, 3.0%)	1.5% (0.4%, 5.9%)
Nipple Complications	1.3% (0.6%, 2.9%)	0% N/A
Hematoma	1.1% (0.4%, 2.5%)	2.0% (0.6%, 6.0%)
Scarring/Hypertrophic Scarring	1.1% (0.5%, 2.7%)	2.7% (1.0%, 7.1%)
Seroma/Fluid Accumulation	1.1% (0.4%, 2.6%)	1.4% (0.4%, 5.6%)
Asymmetry	<1% N/A	5.7% (2.9%, 11.2%)
Delayed Wound Healing	<1% N/A	1.3% (0.3%, 5.1%)
Implant Extrusion	<1% N/A	1.5% (0.4%, 6.0%)
Implant Removal without Replacement	<1% N/A	3.6% (1.5%, 8.5%)
Wrinkling/Rippling	<1% N/A	3.4% (1.4%, 8.0%)
Implant Palpability/Visibility	0% N/A	1.4% (0.3%, 5.4%)
Upper Pole Fullness	0% N/A	1.4% (0.4%, 5.6%)
Breast/Skin Sensation Changes, Bruising, Capsule Calcification, Irritation, Lymphadenopathy, Lymphedema, Palpable Orientation Mark, Pneumothorax, Ptosis, Redness, Skin Rash, Tissue/Skin Necrosis	0 - 1% N/A	0 - 1% N/A

^* Most events were assessed with severity ratings, and the rates shown in the table include only complications rated moderate, severe or very severe (excludes mild and very mild ratings). All occurrences of reoperation, implant removal, implant rupture, implant extrusion, and pneumothorax are included.

Reasons for Reoperation

Table 8 provides the main reason for each reoperation performed through 5 years in primary augmentation and revision-augmentation patients.

Table 8
Pivotal Study: Main Reason for Reoperation through 5 Years

Reason for Reoperation	Primary Augmentation n (% of 96 Reoperations)	Revision- Augmentation N (% of 60 Reoperations)
Patient Request for Style/Size Change	17 (17.7%)	4 (6.7%)
Implant Malposition	14 (14.6%)	10 (16.7%)
Scarring/Hypertrophic Scarring	12 (12.5%)	7 (11.7%)
Hematoma/Seroma	9 (9.4%)	3 (5.0%)
Ptosis	9 (9.4%)	6 (10.0%)
Capsular Contracture	7 (7.3%)	9 (15.0%)
Need for Biopsy	6 (6.3%)	6 (10.0%)
Asymmetry	4 (4.2%)	3 (5.0%)
Breast Cancer	4 (4.2%)	0
Infection	4 (4.2%)	4 (6.7%)
Suspected Rupture/Gel Fracture	4 (4.2%)	3 (5.0%)
Delayed Wound Healing	3 (3.1%)	1 (1.7%)
Implant Extrusion	1 (1.0%)	1 (1.7%)
Nipple Complications, Wrinkling	1 each (1.0%)	0
Breast Pain	0	2 (3.3%)
Implant Palpability/Visibility	0	1 (1.7%)
Total	96 (100%)	60 (100%)

Reasons for Implant Removal

The main reasons for implant removal among primary augmentation and revision-augmentation patients over the 5 years are shown in Table 9.

Table 9
Pivotal Study: Main Reason for Implant Removal through 5 Years

Reason for Removal	Primary Augmentation n (% of 68 Explants)	Revision- Augmentation n (% of 47 Explants)
Patient Request for Style/Size Change	35 (51.5%)	11 (23.4%)
Ptosis	10 (14.7%)	2 (4.3%)
Asymmetry	6 (8.8%)	4 (8.5%)
Suspected Rupture/Gel Fracture	5 (7.4%)	3 (6.4%)
Infection	3 (4.4%)	4 (8.5%)
Capsular Contracture	2 (2.9%)	11 (23.4%)
Hematoma/Seroma	2 (2.9%)	0
Implant Malposition	2 (2.9%)	6 (12.8%)
Implant Extrusion	1 (1.5%)	1 (2.1%)
Need for Biopsy, Wrinkling/Rippling	1 each (1.5%)	0
Breast Pain	0	2 (4.3%)
Implant Palpability/Visibility	0	2 (4.3%)
Scarring/Hypertrophic Scarring	0	1 (2.1%)
Total	68 (100%)	47 (100%)

Other Events

Through 5 years, events other than the complications described in the previous tables were collected in the pivotal study for augmentation and revision-augmentation patients. Some of these events, such as breast cancer and CTD, can occur in non-implanted patients. Therefore, without a comparison group of women with similar characteristics (such as age, race, etc.) and without breast implants, no conclusions can be made about the relationship between breast implants and some of these other events.

Benign breast disease occurred in 2% of primary augmentation patients and in 7% of revision-augmentation patients. Malignant breast disease occurred in 0.7% and 0.8% of primary augmentation and revision-augmentation patients, respectively. CTD events were 1% or less.

9.2.2 Reconstruction and Revision-Reconstruction Patients

Described below are the benefits and complications reported in the pivotal study for reconstruction and revision-reconstruction patients.

Allergan's results indicate that the risk of any complication at some point through 5 years after implant surgery is 47% for primary reconstruction patients and 51% for revision-reconstruction patients. However, the majority of women were satisfied with their implants. The results also indicate that the chance of additional surgery (reoperation) through the first 5 years is slightly more than 1 in 3 for primary reconstruction patients (with implant removal and replacement as the most common type of additional surgery), and 1 in 4 for revision-reconstruction patients (with implant removal and replacement as the most common type of additional surgery). The information below provides more details about the complications and benefits of Highly Cohesive Shaped breast implants.

Patient Accounting (Follow-Up Rates)

The pivotal study enrolled 225 reconstruction patients. Of the women expected to be seen at the 5-year follow-up visit, 91% were seen.

The pivotal study enrolled 68 revision-reconstruction patients. Of the women expected to be seen at the 5-year follow-up visit, 85% were seen.

Effectiveness Outcomes

The benefits of Highly Cohesive Shaped implants were assessed by a variety of outcomes, including assessments of patient satisfaction, body image, body esteem, and self concept. Data were collected before implantation and at scheduled follow-up visits. Quality of life data were collected through the first two years after implantation.

Primary Reconstruction Patients:
Patient satisfaction was based on a 5-point scale assessment of satisfaction with their implants at the time of the follow-up visits. 170 (76%) of the original 225 patients provided a satisfaction rating at 5 years after implantation with 92% of these patients indicating that they were satisfied with their breast implants.

For primary reconstruction patients, the SF-36, which measures mental and physical health, showed a slight worsening in one scale after 2 years compared to before breast implantation. For patient responses to questions regarding overall self-concept/self-esteem, there was no change in self-concept on the Tennessee Self Concept Scale and no change in overall self esteem on the Rosenberg Self Esteem Scale 2 years after receiving implants. Patient responses to questions on the Body Esteem Scale regarding overall body image also did not show a change 2 years after receiving implants. On the Rowland Expectation Scale patients showed significant improvement in well-being. Breast satisfaction was increased after 2 years, including satisfaction with breast shape, size, feel or touch, and how well they matched.

Revision-Reconstruction Patients:
Patient satisfaction was based on a 5-point scale assessment of satisfaction with their implants at the time of the follow-up visits. 51 (75%) of the original 68 revision-reconstruction patients provided a satisfaction rating at 5 years. Of these 51 patients, 82% indicated that they were satisfied with their breast implants.

Effectiveness measures such as the SF-36 assess the effect of implantation on quality of life which is not feasible for revision-reconstruction patients who have pre-existing implants prior to enrollment in the study. Therefore, these assessments were not performed for revision-reconstruction patients.

Safety Outcomes

Table 10 describes the complications experienced by primary reconstruction and revision-reconstruction patients in the pivotal study.

Table 10
Pivotal Study: Complications
5-Year Cumulative First Occurrence Kaplan-Meier Risk Rates, By Patient

Complication*	Primary Reconstruction N = 225 Rate (%)(95% CI)	Revision-Reconstruction N = 68 Rate (%)(95% CI)
Reoperation	39.4% (33.2%, 46.2%)	28.8% (19.4%, 41.4%)
Implant Removal with Replacement	19.0% (14.3%, 25.0%)	18.3% (10.8%, 30.0%)
Capsular Contracture	9.6% (6.2%, 14.6%)	14.3% (7.7%, 25.8%)
Asymmetry	9.1% (5.9%, 13.9%)	13.1% (6.8%, 24.7%)
Implant Rupture (MRI Cohort)	7.2% (3.0%, 16.4%)	9.5% (2.5%, 33.0%)
Hypertrophic/Other Abnormal Scarring	4.8% (2.6%, 8.7%)	3.2% (0.8%, 12.3%)
Infection	4.8% (2.6%, 8.8%)	4.5% (1.5%, 13.3%)
Implant Removal without Replacement	4.6% (2.4%, 8.7%)	0% N/A
Other Complications	4.4% (2.3%, 8.4%)	1.7% (0.2%, 11.4%)
Upper Pole Fullness	4.2% (2.2%, 7.8%)	1.5% (0.2%, 10.1%)
Swelling	3.8% (1.9%, 7.5%)	3.3% (0.8%, 12.5%)
Breast Pain	3.5% (1.7%, 7.3%)	3.5% (0.9%, 13.1%)
Implant Malposition	2.9% (1.3%, 6.3%)	4.9% (1.6%, 14.5%)
Wrinkling/Rippling	2.5% (1.0%, 5.8%)	7.7% (3.3%, 17.4%)
Seroma/Fluid Accumulation	1.4% (0.5%, 4.3%)	6.2% (2.4%, 15.8%)
Hematoma	1.0% (0.3%, 4.0%)	0% N/A
Delayed Wound Healing	<1% N/A	2.9% (0.7%, 11.3%)
Nipple Complications	<1% N/A	1.7% (0.2%, 11.2%)
Redness	<1% N/A	2.9% (0.7%, 11.3%)
Tissue/Skin Necrosis	<1% N/A	1.5% (0.2%, 10.0%)
Implant Extrusion	<1% N/A	0% N/A
Bruising	0% N/A	1.5% (0.2%, 10.0%)
Implant Palpability/Visibility	0% N/A	1.5% (0.2%, 10.3%)
Breast/Skin Sensation Changes, Capsule Calcification, Irritation, Lymphadenopathy, Lymphedema, Palpable Orientation Mark, Pneumothorax, Ptosis, Skin Rash	0% N/A	0% N/A

^* Most events were assessed with severity ratings, and the rates shown in the table include only complications rated moderate, severe or very severe (excludes mild and very mild ratings). All occurrences of reoperation, implant removal, implant rupture, implant extrusion, and pneumothorax are included.

Reasons for Reoperation

Table 11 provides the main reason for each reoperation performed through 5 years in primary reconstruction and revision-reconstruction patients.

Table 11
Pivotal Study: Main Reason for Reoperation through 5 Years

Reason for Reoperation	Primary Reconstruction n (% of 113 Reoperations)	Revision- Reconstruction n (% of 24 Reoperations)
Scarring/Hypertrophic Scarring	27 (23.9%)	1 (4.2%)
Implant Malposition	14 (12.4%)	3 (12.5%)
Capsular Contracture	14 (12.4%)	4 (16.7%)
Patient Request for Style/Size Change	12 (10.6%)	4 (16.7%)
Infection	9 (8.0%)	1 (4.2%)
Asymmetry	7 (6.2%)	2 (8.3%)
Breast Tissue Contour Deformity	5 (4.4%)	0
Ptosis	5 (4.4%)	0
Need for Biopsy	4 (3.5%)	1 (4.2%)
Suspected Rupture	4 (3.5%)	0
Breast Pain	3 (2.7%)	0
Wrinkling	3 (2.7%)	2 (8.3%)
Hematoma/Seroma	2 (1.8%)	1 (4.2%)
Implant Extrusion	2 (1.8%)	0
Breast Cancer Mass	1 (0.9%)	0
Necrosis	1 (0.9%)	0
Delayed Wound Healing	0	3 (12.5%)
Nipple Complications	0	2 (8.3%)
Total	113 (100%)	24 (100%)

Reasons for Implant Removal

The main reasons for implant removal among primary reconstruction and revision-reconstruction patients in the pivotal study over the 5 years are shown in Table 12.

Table 12
Pivotal Study: Main Reason for Implant Removal through 5 Years

Reason for Removal	Primary Reconstruction % (of 68 Explants)	Revision- Reconstruction % (of 19 Explants)
Patient Request for Style/Size Change	22 (32.4%)	7 (36.8%)
Capsular Contracture	11 (16.2%)	3 (15.8%)
Asymmetry	8 (11.8%)	1 (5.3%)
Infection	6 (8.8%)	1 (5.3%)
Implant Malposition	5 (7.4%)	2 (10.5%)
Breast Pain	4 (5.9%)	0
Wrinkling	5 (7.4%)	4 (21.1%)
Implant Extrusion	2 (2.9%)	0
Suspected Rupture	2 (2.9%)	0
Breast Tissue Contour Deformity, Hematoma/Seroma, Ptosis,	1 each (1.5%)	0
Delayed Wound Healing	0	1 (5.3%)
Total	68 (100%)	19 (100%)

Other Events

Through 5 years, events other than the complications described in the previous tables were collected in the pivotal study for reconstruction and revision-reconstruction patients. Some of these events, such as breast cancer and CTD, can occur in non-implanted patients. Therefore, without a comparison group of women with similar characteristics (such as age, race, etc.) and without breast implants, no conclusions can be made about the relationship between breast implants and some of these other events.

Benign breast disease occurred in 4% of primary reconstruction. Malignant breast cancer was determined in 3% of primary reconstruction patients and 1.5% of revision-reconstruction patients. CTD events were less than 1% for primary reconstruction patients with no CTDs detected in revision-reconstruction patients.

Continued Access Clinical Study

One of the ongoing Allergan US studies, the Continued Access study, has enrolled to date 2,274 primary augmentation patients, 506 revision-augmentation patients, 469 primary reconstruction patients and 288 revision-reconstruction patients. Similar results to those discussed in detail above were obtained through 3 years of the 10 year study.

The most common complications for primary augmentation patients included capsular contracture (2%) and implant malposition (2%), with all other complications occurring at less than 2%. For revision-augmentation patients, the most common complications were also capsular contracture (5%) and implant malposition (3%). The most common complications for primary reconstruction patients included asymmetry (8%) and capsular contracture (7%), with all other complications occurring at less than 5%. For revision-reconstruction patients, the most common complications were also capsular contracture (6%) and asymmetry (6%).

Greater than 96% of primary augmentation patients and greater than 92% of revision-augmentation patients in the Continued Access study indicated they were satisfied with their implants through 3 years. Satisfaction rates for both primary reconstruction and revision-reconstruction patients were 90% or greater through 3 years.

10 Instructions for Use

NOTE: Back-up breast implants should be available during the procedure.

DO NOT use more than one implant per breast.

10.1 Single Use

This product is intended for single use only. Do not reuse explanted implants.

10.2 Product Identification

Product identification stickers accompanying each device are provided within the internal product packaging. The stickers provide product-specific information and are designed to be attached to the patient's chart for identification purposes.

10.3 Surgical Planning

Allergan relies on the surgeon to know and follow the proper surgical procedures with NATRELLE^TM Silicone-Filled Breast Implants. Proper surgical planning such as allowance for adequate tissue coverage, implant placement (i.e., submuscular vs. subglandular), incision site, implant type, etc., should be made preoperatively. The surgeon should be aware that the unique nature of the highly cohesive gel may require a larger incision compared to the incision size required for other silicone-filled implants to avoid skin edge trauma or implant deformation. Excessive force upon insertion of the implant may compromise the precisely defined shape of the device, potentially leading to an undesirable cosmetic outcome. The surgeon must carefully evaluate breast implant size and contour, incision placement, pocket dissection, and implant placement criteria with respect to the patient's anatomy and desired physical outcome.

The surgeon should be aware that more upper pole fullness may be maintained by the Highly Cohesive Shaped implant than with other breast implants. Planning should include clear delineation of aesthetic goals to ensure mutual understanding between surgeon and patient. The surgeon should observe current and accepted techniques to minimize the risk of adverse, and potentially disfiguring, reactions, bearing in mind the importance of pocket dissection in minimizing implant rotation for the shaped Highly Cohesive implant.

10.4 Preliminary Product Examination

How to Open Sterile Product Package

Remove the sterile breast implant from its package in an aseptic environment and using talc-free gloved hands. DO NOT expose the breast implant to lint, talc, sponges, towels, skin oils, or other contaminants.

1. Peel open the lid of the outer thermoform package.
2. Invert the outer thermoform package over the sterile field, allowing the sealed inner thermoform package to gently fall into the field.
3. Peel open the lid of the inner thermoform package using the pull-tab.
4. Gently retrieve the breast implant. Prior to use, keep the breast implant in the inner thermoform package to prevent contact with airborne and surgical field particulate contaminants.

Examination of Silicone-Filled Breast Implants

Prior to use, examine the breast implant for evidence of any particulate contamination, damage, or loss of shell integrity. If satisfactory, return the breast implant to the inner thermoform tray and cover it with the lid until implanted to prevent contact with airborne contaminants.

DO NOT implant any device that may appear to have particulate contamination, damage, or loss of shell integrity. A sterile back-up implant must be readily available at the time of surgery.

DO NOT implant any device that may appear to have leaks or nicks.

DO NOT implant damaged or contaminated breast implants.

10.5 Sterile Product

Each sterile silicone-filled breast implant is supplied in a sealed, double primary package. Sterility of the implant is maintained only if the thermoform packages, including the package seals, are intact. Use standard procedures to maintain sterility during transfer of the breast implant to the sterile field. Remove the breast implant from its package in an aseptic environment and using talc-free gloved hands.

DO NOT use the product if the thermoform packages or seals have been damaged.

DO NOT resterilize the product.

Prior to use, keep the breast implant in the inner thermoform and covered to prevent contact with airborne and surgical field particulate contaminants.

10.6 Method for Removing Ruptured Silicone Gel from the Surgical Pocket

In the event of breast implant rupture, the following technique is useful for removal of the silicone mass. Wearing double talc-free surgical gloves on one hand, use the index finger to penetrate the silicone mass. With the other hand, exert pressure on the breast to facilitate manipulation of the silicone mass into the double-gloved hand. Once the silicone is in hand, pull the outer glove over the silicone mass and remove. To remove any residual silicone, blot the surgical pocket with gauze sponges. Avoid contact between surgical instruments and the silicone. If contact occurs, use isopropyl alcohol to remove the silicone from the instruments. Ruptured breast implants must be reported and should be returned to Allergan. In the event of breast implant rupture, contact Allergan's Product Support Department at 1.800.624.4261.

10.7 Surgical Procedure Placement

Ensure incision is sufficiently large to facilitate insertion without excessive manipulation and handling of the device and to avoid damage to the device. Inadequate pocket dissection increases the risk of rupture and implant malposition.

Orientation Dots

Highly Cohesive Shaped breast implants have orientation marks that are circular silicone elastomer dots located on the surface of the implant. They are used to assist with visual and tactile placement of the implant within the surgical pocket. The posterior surface of most sizes of Highly Cohesive Shaped implants has 4 orientation marks; the posterior surface of some smaller and/or shorter styles may have only 3 orientation marks. The anterior surface of all Highly Cohesive Shaped implants has 2 orientation marks.

DO NOT damage the breast implant with sharp surgical instruments such as needles and scalpels, blunt instruments such as clamps and forceps, or by over handling and manipulation during introduction into the surgical pocket.

DO NOT use excessive force during breast implant placement.

DO NOT manipulate the implant for either radial expansion, compression or dissection of the pocket.

Breast augmentation with silicone-filled implants can be carried out through several different incisions including inframammary, periareolar, or transaxillary. Some surgeons advocate a "no-touch" technique, which requires significant attention to minimizing contact between the patient's skin and the implant. Pocket dissection should be planned out preoperatively and be performed accurately and with minimal trauma. Excellent hemostasis is important to avoid postoperative hematoma. The implant may be placed subglandularly or subpectorally depending upon the balance of cosmetic and medical considerations in any given patient. The size and shape of the device may be determined preoperatively by means of dimensional planning or intraoperatively with the help of temporary sizer devices.

The incision for the placement of the implant should be securely closed and in several layers, whenever possible. Drains are optional.

Breast Reconstruction is generally carried out in the mastectomy scar. Special care must be used in breast reconstruction to make sure that appropriate amounts of healthy tissue are available to cover the implant and that the implant be properly sized and positioned based upon careful preoperative planning.

Allergan Academy^TM Educational Materials are available through www.allerganacademy.com or www.allerganacademy.ca to supplement surgical knowledge of the dimensional techniques intended for use with NATRELLE^TM breast implants.

Maintaining Hemostasis/Avoiding Fluid Accumulation

Postoperative hematoma and seroma may be minimized by meticulous attention to hemostasis during surgery, and possibly also by postoperative use of a closed drainage system. Persistent, excessive bleeding must be controlled before implantation.

Any postoperative evacuation of hematoma or seroma must be conducted with care to avoid breast implant contamination or damage from sharp instruments.

11 Documentation the Physician Should Provide to the Patient

Breast implantation is an elective procedure and the patient must be well counseled on the risk-benefit relationship. The surgeon should provide each prospective patient with the following:

• Bilingual Patient Planner for Breast Augmentation or Reconstruction with NATRELLE^TM Silicone-Filled Breast Implants
  This planner should be used to facilitate patient education on the risks and benefits of silicone gel-filled breast implant surgery. The entire planner should be given to the patient during her initial visit/consultation to allow sufficient time for review. You should verify that the patient has an adequate understanding of the information provided by evaluating the Patient Self Assessment and using this as a foundation for subsequent preoperative discussion.
  
  
• Device Identification Card
  Enclosed with each silicone-filled breast implant is Allergan's Device Identification Card. To complete the Device Identification Card, place one device identification sticker for each implant on the back of the card. Stickers are located on the internal product packaging attached to the label. If a sticker is unavailable, the lot number, catalog number and description of the device may be copied by hand from the device label. Patients should be provided with these cards for personal reference.

12 Additional Specific Product Information

12.1 Returned Goods Policy

Product returns should be handled through an Allergan Breast Aesthetics Sales Associate or through the Customer Care Department at 1.800.624.4261. Return value is based on time limitations. All package seals must be intact to be eligible for return. Returned products may be subject to a restocking charge.

12.2 Reporting and Return of Explanted Devices

The reason for explantation should be reported and the explanted device returned to Allergan. In the event of an explantation, please contact Allergan's Product Support Department at 1.800.624.4261 for an Explant Kit and explant return instructions.

12.3 ConfidencePlus^® Limited Warranties

The ConfidencePlus^® Limited Warranties provide lifetime replacement and limited financial reimbursement in the event of shell leakage or breakage resulting in implant rupture, subject to certain conditions as fully discussed in the ConfidencePlus^® literature. Allergan offers two levels of coverage under its warranty program. Our standard ConfidencePlus^® Limited Warranty program applies automatically to every NATRELLE^TM breast implant recipient subject to the conditions discussed in the ConfidencePlus^® literature. The optional ConfidencePlus^® Premier Limited Warranty program is available for a low enrollment fee and increases the financial benefit in the event of implant rupture, subject to the conditions discussed in the ConfidencePlus^® literature. For more information, please visit www.cppwarranty.com or contact Allergan's Product Support Department at 1.800.624.4261.

12.4 Product Ordering

To order directly in Canada or for product information, please contact your local Allergan Breast Aesthetics Sales Associate or the Allergan Customer Care Department at 1.800.624.4261.

13 Literature References

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2. Bondurant, S., V.L. Ernster and R. Herdman, Eds. 2000. Safety of silicone breast implants. Committee on the Safety of Silicone Breast Implants, Division of Health Promotion and Disease Prevention, Institute of Medicine. Washington, D.C.: National Academy Press.
3. Breiting, V.B., et al. 2004. Long-term health status of Danish women with silicone breast implants. Plast. Reconstr. Surg. 114:217-26.
4. Brinton, L.A., et al. 2001a. Mortality among augmentation mammoplasty patients. Epidemiology. 12(3):321-6.
5. Brinton, L.A., et al. 2000. Breast cancer following augmentation mammoplasty (United States). Cancer Causes Control. 11(9):819-27.
6. Brinton, LA., et al. 2001b. Cancer risk at sites other than the breast following augmentation mammoplasty. Ann. Epidemiol. 11:248-56.
7. Brinton, L.A., et al. 2004. Risk of connective tissue disorders among breast implant patients. Am. J. Epidemiol. 160(7):619-27.
8. Brown, S.L., et al. 2001. Silicone gel breast implant rupture, extracapsular silicone, and health status in a population of women. J. Rheumatol. 28:996-1003.
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10. Cook, L.S. 1997. Characteristics of women with and without breast augmentation. JAMA. 20:1612-7.
11. Deapen, D.M., et al. 1997. Are breast implants anticarcinogenic? A 14-year follow-up of the Los Angeles Study. Plast. Reconstr. Surg. 99(5):1346-53.
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These products are covered by one or more of the following U.S. Patents: 5,480,430; 5,007,929; 4,889,744 and 4,859,712 and/or foreign patents corresponding thereto.

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