1 INDICATIONS AND USAGE

SUSVIMO (ranibizumab injection) is indicated for the treatment of patients with Neovascular (wet) Age-related Macular Degeneration (AMD) who have previously responded to at least two intravitreal injections of a Vascular Endothelial Growth Factor (VEGF) inhibitor medication.

2 DOSAGE AND ADMINISTRATION

2.4 Ocular Implant Initial Fill

The implant initial fill procedure must be performed by a physician experienced in vitreoretinal surgery [see Dosage and Administration (2.1)]. The implant will be filled using aseptic technique with 0.02 mL of SUSVIMO (ranibizumab injection) prior to insertion of the implant into the patient's eye [see Dosage and Administration (2.5)]. Refer to the complete SUSVIMO Instructions for Use for the initial fill and implant procedure included in the insertion tool assembly carton for further details.

Use aseptic technique to carry out the following preparation steps prior to insertion of the ocular implant into the patient's eye:

Step 1: Gather the supplies needed. One SUSVIMO ocular implant with insertion tool assembly (included) One SUSVIMO initial fill needle (34-gauge with integrated 5 μm filter) with blue cap (included) One SUSVIMO (ranibizumab injection) 100 mg/mL vial (included) One sterile 5-micron filter needle (19-gauge × 1½ inch) (not included) One sterile 1 mL Luer Lock syringe (not included)
Step 2: Transfer Dose from Vial to Syringe
Note:	Use the filter needle (not included) to withdraw SUSVIMO (ranibizumab injection) from the vial.	Figure 1
Do not use the SUSVIMO initial fill needle for this step. Prepare SUSVIMO (ranibizumab injection) vial by removing the flip-off cap and disinfecting the rubber vial septum with alcohol. Attach a filter needle to the syringe by screwing it tightly onto the Luer lock (see Figure 1). Carefully remove the needle cap by pulling it straight off. Using aseptic technique, withdraw all of the contents of the SUSVIMO (ranibizumab injection) vial through the filter needle into the syringe.
Step 3: Remove Air from Syringe With the filter needle attached, hold the syringe with the needle pointing up. If there are any air bubbles, gently tap the syringe with your finger until the bubbles rise to the top (Figure 2). Slowly push the plunger rod just until all air is expelled from the syringe and needle. – It is important to preserve as much drug as possible in order to completely fill the implant. Remove and properly dispose of the filter needle after air is removed from syringe.		Figure2
Step 4: Attach SUSVIMO Initial Fill Needle Do not use the filter needle to fill the implant. Attach the SUSVIMO initial fill needle (included) firmly onto the syringe by screwing it tightly onto the Luer lock (see Figure 3). Ensure that the initial fill needle is attached to the syringe. Carefully remove the needle cap by pulling straight off. Do not wipe the needle at any time.		Figure 3
Step 5: Remove Any Remaining Air from Syringe With the initial fill needle attached, hold the syringe with the needle pointing up. If there are any air bubbles, gently tap the syringe with your finger until the bubbles rise to the top (see Figure 4). Slowly push the plunger rod just until all air is expelled from the syringe and needle, and a drop of drug solution is seen at the needle tip (see Figure 5).		Figure 4 Figure 5
Note:	It is important to preserve as much drug as possible in order to completely fill the implant.
Step 6: Inspect the Syringe for Air Bubbles Inspect the syringe and the needle hub to ensure that no air bubbles are present (see Figure 6). If air bubbles are present, continue to remove air from the syringe and reinspect.		Figure 6
Note:	Use the syringe within 15 minutes of removing all air to avoid ranibizumab drying in the needle and impeding fluid flow. Do not use the initial fill needle if the needle is clogged.
Step 7: Load Syringe into the Carrier Do not hold or push on the plunger rod of the syringe while inserting the needle into the implant septum. Retrieve insertion tool carrier with pre-positioned implant from the inner tray. Align the syringe Luer lock above the Luer lock slot in the carrier to protect the needle from being damaged. Lower the syringe into the carrier (see Figure 7). Push the syringe forward until it stops, taking care to avoid touching the plunger rod (see Figure 8) With the syringe loaded, (see Figure 9) the initial fill needle should now be penetrating the implant septum.		Figure 7: Align and lower the syringe into the carrier Figure 8: Push the syringe into the carrier Figure 9: Syringe with initial fill needle inserted through the implant septum
Step 8: Fill Ocular Implant with SUSVIMO (ranibizumab injection) Under Microscope Under the microscope, slowly administer SUSVIMO (ranibizumab injection) into the ocular implant by slightly tilting the carrier upwards (see Figure 10). The ocular implant should be filled over approximately 5 to 10 seconds, to help avoid air entrapment in the implant reservoir.		Figure 10: Administer ranibizumab into the implant Figure 11: Dome of drug solution forms at tip of implant as viewed under magnification
Note:	When filling the ocular implant, drug solution should only exit the ocular implant from the release control element. If drug solution is leaking from the implant at a different location, such as the side of the implant, do not use the ocular implant. If fluid is leaking from the septum at the needle insertion site, the needle may not be fully penetrating the implant septum. Fully push the syringe forward before continuing to fill the ocular implant.
Continue filling the ocular implant until the implant is completely full of drug solution and all air has been expelled as evidenced by a dome of drug solution formed at the tip of the implant on the release control element (see Figure 11).
Step 9: Inspect the Filled Ocular Implant Under the Microscope Inspect the ocular implant under the microscope to ensure that the ocular implant is completely full of drug solution (see Figure 12).		Figure 12: Proper appearance of implant after initial filling with ranibizumab
Note:	Minimize air bubbles within the implant reservoir as they may cause slower drug release. If an air bubble is present, it must be no larger than 1/3 of the widest diameter of the implant. If excess air is observed, do not use the ocular implant.
Note:	No more than 30 minutes should pass between the initial fill of the implant and the insertion into the patient's eye to ensure that the release control element remains saturated with SUSVIMO (ranibizumab injection). If SUSVIMO (ranibizumab injection) dries in the release control element, the implant may not release the drug properly into the vitreous after insertion.
Step 10: Remove the Syringe and Guide Sleeve from the Carrier Remove the syringe and guide sleeve from the carrier by pulling back on the syringe (see Figure 13). The syringe will be locked into the guide sleeve. Properly dispose of the used syringe together with the needle and guide sleeve in a sharps disposal container or in accordance with local requirements.		Figure 13: Remove the syringe and guide sleeve from the insertion tool carrier
Step 11: Slide the Insertion Tool Handle into the Carrier Slide the insertion tool handle into the guide channel of the carrier, ensuring that both components are facing upwards (see Figure 14). Push the handle forward as far as it will go into the gripper tips (see Figure 15).		Figure 14: Insert the handle into the insertion tool carrier Figure 15: Fully inserted handle
Note:	Do not withdraw the handle and implant until the eye is ready for insertion. Contact between the implant and any surface or object – even within the sterile field – may result in the introduction of a foreign body into the vitreous.

2.7 Ocular Implant Refill-Exchange Procedure

The SUSVIMO ocular implant refill-exchange procedure must be performed under strict aseptic conditions by a physician experienced in ophthalmic surgery [see Dosage and Administration (2.1)]. This includes the use of a surgical mask, sterile gloves, and a lid speculum.

Prior to and after the refill-exchange procedure, perform a dilated slit lamp exam and/or dilated indirect ophthalmoscopy to inspect the implant in the vitreous cavity through the pupil to identify if dislodgement of the implant septum has occurred [see Figure 31 and Warnings and Precautions (5.4)]. If the septum has dislodged, any further refill-exchange procedures should not be performed because normal device functioning cannot be assured. Discontinue treatment with SUSVIMO (ranibizumab injection) following septum dislodgement and consider implant removal should the benefit of the removal procedure outweigh the risk.

Step 1: Gather the supplies needed. One SUSVIMO Refill Needle (34-gauge with a 5 µm integrated filter) with clear cap (included) One SUSVIMO (ranibizumab injection) 100 mg/mL vial (included) One sterile 1 mL Luer Lock syringe (not included) One sterile 5-micron filter needle (19-gauge × 1½ inch) (not included) Additional materials required to perform the procedure but are not provided are: Anesthetic ophthalmic solutions Ophthalmic broad-spectrum microbicide solution Cotton tips and gauze Sterile powder free gloves Face masks Lid speculum Magnification such as visor or loupes Task lighting Indirect ophthalmoscope and lens Sterile drape (optional for refill-exchange procedure)
Step 2: Inspect Packaging and Components Prior to use in the clinic, inspect the packaging of the components for damage. Do not use if the sterility has been compromised or the contents have been dropped, damaged, or tampered with. Check the expiration date printed on the label. Remove the vial from the carton. Note: the outside of the vial is not sterile. Use aseptic technique to open packaging and remove the sterile refill needle from the tray. Inspect components and place onto sterile field (see Figure 16).		Figure 16
Step 3: Inspect SUSVIMO (ranibizumab injection) Visually inspect the contents of the SUSVIMO (ranibizumab injection) vial for particulate matter and discoloration. SUSVIMO should be colorless to pale brown Do not use if particulate, cloudiness, or discoloration are visible.
Step 4: Patient Preparation Dilate the pupil of the eye. Perform slit lamp examination and/or indirect ophthalmoscopy to inspect the implant and its components in the vitreous cavity through the dilated pupil. Position the patient on exam chair in the supine position at approximately 20° to 30° angle for optimal visualization of the implant. Apply a broad-spectrum microbicide to the periocular skin, eyelid, and ocular surface prior to the refill-exchange procedure. The use of a sterile drape is up to the physician's discretion. Perform the procedure under topical anesthesia. If needed, subconjunctival anesthesia may be administered in the nasal quadrant, away from the implant.
Step 5: Transfer Dose from Vial to Syringe		Figure 17
Note:	Use the filter needle to withdraw SUSVIMO (ranibizumab injection) from the vial.
Do not use the SUSVIMO refill needle for this step. Prepare ranibizumab vial by removing the flip-off cap and disinfecting the rubber vial septum with alcohol. Attach a filter needle to the syringe by screwing it tightly onto the Luer lock (see Figure 17). Carefully remove the needle cap by pulling it straight off. Using aseptic technique, withdraw all of the contents of the SUSVIMO (ranibizumab injection) vial through the filter needle into the syringe.
Step 6: Remove Air from Syringe With the filter needle attached, hold the syringe with the needle pointing up. If there are any air bubbles, gently tap the syringe with your finger until the bubbles rise to the top (Figure 18). Slowly push the plunger rod just until the air is expelled from the syringe and needle. – It is important to preserve as much drug as possible in order to completely refill the implant Remove and properly dispose of the filter needle after air is removed from the syringe.		Figure 18
Step 7: Attach SUSVIMO Refill Needle Do not use the filter needle to fill the implant. Attach the SUSVIMO refill needle firmly onto the syringe by screwing it tightly onto the Luer lock (see Figure 19). Ensure that the refill needle is attached to the syringe. Carefully remove the needle cap, pulling straight off to avoid damage to the needle cannula. Do not wipe the needle at any time.		Figure 19
Step 8: Remove Any Remaining Air from Syringe and Adjust Drug Dose With the refill needle attached, hold the syringe with the needle pointing up. If there are any air bubbles, gently tap the syringe with your finger until the bubbles rise to the top (see Figure 20). Slowly push the plunger rod until all air is expelled from the syringe and needle and the uppermost edge of the black plunger tip is aligned with the 0.1 mL dose mark (see Figure 21).		Figure 20 Figure 21
Step 9: Inspect the Syringe for Air Bubbles		Figure 22
Note:	Ensure no air bubbles are present in the syringe and needle hub. Air injected into the implant could result in slower drug release.
Inspect the syringe and the needle hub using magnification to ensure that no air bubbles are present (see Figure 22).
Note:	Use the syringe within 15 minutes of removing all air and adjusting the drug dose to avoid drug solution drying in the needle and impeding fluid flow. Do not use the refill needle or syringe if the needle is clogged.
Step 10: Stabilize the globe and orient the refill needle		Figure 23Figure 24
Note:	Perform the refill-exchange procedure using magnification (e.g., loupes, reading glasses, magnifiers) for visual assistance.
After placing the lid speculum in the eye, stabilize the globe with a cotton-tipped applicator to minimize eye movement (see Figure 23). – Recommend standing on the contralateral side of the implanted eye, with the patient looking down and toward their nose to optimally expose the implant. Orient the refill needle perpendicular to the globe (see Figure 24).
Step 11: Insert the Refill Needle		Figure 25 Figure 26
Note:	Insert needle at the very center of the implant septum and perpendicular to the implant to ensure the needle inserts fully. Do not maneuver if there is resistance as it will bend the needle. Do not use a bent refill needle; replace if bent or if damage is suspected.
Targeting the center of the implant septum, insert the refill needle perpendicularly through the conjunctiva and into the implant septum (see Figure 25). – If excessive resistance, withdraw the refill needle. Orient and insert again. – Do not twist when encountering conjunctiva and Tenon's capsule to gain access to the septum, as damage to the overlying tissue and to the septum of the device may result. Continue inserting the needle until the soft stop of the refill needle makes physical contact with the conjunctiva (see Figure 26) to provide a tactile cue that optimal contact has been made.
Step 12: Refill the SUSVIMO Implant Refill the implant slowly, by delivering the entire contents of the syringe into the implant, over approximately 5 to 10 seconds, to avoid pressure build-up in the implant reservoir. The soft stop of the refill needle must remain in contact with the conjunctiva throughout the procedure. As ranibizumab is administered into the implant, existing solution from the implant should immediately begin to fill the refill needle fluid collection chamber (see Figure 27). If fluid is not observed collecting in the refill needle fluid collection reservoir, stop injecting and ensure the refill needle is inserted into the center of the implant septum at a perpendicular angle and the soft stop is in contact with the conjunctiva. Administer all of the syringe contents in order to achieve the target replacement ranibizumab concentration in the implant reservoir.		Figure 27
Step 13: Withdraw the Syringe Withdraw the syringe perpendicular to the globe to avoid damaging the septum (see Figure 28). A cotton-tipped applicator may be used to provide counter traction to the conjunctiva during needle withdrawal.		Figure 28
Step 14: Dispose of the Used Components Do not recap the needle or detach it from the syringe. Dispose of the used syringe together with the refill needle in a sharps disposal container or in accordance with local requirements.
Step 15: Perform Indirect Ophthalmoscopy Perform dilated indirect ophthalmoscopy (and slit lamp exam as needed) to ensure continued proper position of the implant and its components (e.g., septum) in the vitreous cavity and to examine for complications.

3 DOSAGE FORMS AND STRENGTHS

Injection: 100 mg/mL, clear to slightly opalescent, colorless to pale brown solution in a single-dose vial

4 CONTRAINDICATIONS

5 WARNINGS AND PRECAUTIONS

The SUSVIMO implant and/or implant-related procedures have been associated with endophthalmitis, rhegmatogenous retinal detachment, implant dislocation, septum dislodgement, vitreous hemorrhage, conjunctival erosion, conjunctival retraction, and conjunctival blebs. Patients should be instructed to report any signs or symptoms that could be associated with these events without delay. In some cases, these events can present asymptomatically. The implant and the tissue overlying the implant flange should be monitored routinely following the implant insertion, and refill-exchange procedures to permit early medical or surgical intervention as necessary. Special precautions need to be taken when handling SUSVIMO components [see How Supplied/Storage and Handling (16.3)].

6 ADVERSE REACTIONS

The following adverse reactions are discussed in greater detail in other sections of the label:

• Endophthalmitis [see Warnings and Precautions (5.1)]
• Rhegmatogenous Retinal Detachment [see Warnings and Precautions (5.2)]
• Implant Dislocation [see Warnings and Precautions (5.3)]
• Vitreous Hemorrhage [see Warnings and Precautions (5.5)]
• Conjunctival Erosion or Retraction [see Warnings and Precautions (5.6)]
• Conjunctival Bleb [see Warnings and Precautions (5.7)]
• Postoperative Decrease in Visual Acuity [see Warnings and Precautions (5.8)]

8 USE IN SPECIFIC POPULATIONS

11 DESCRIPTION

Ranibizumab is a recombinant humanized IgG1 kappa isotype monoclonal antibody fragment for intraocular use. Ranibizumab binds to and inhibits the biologic activity of human vascular endothelial growth factor-A (VEGF-A). Ranibizumab, which lacks an Fc region, has a molecular weight of approximately 48 kilodaltons and is produced by an E. coli expression system in a nutrient medium containing the antibiotic tetracycline. Tetracycline is not detectable in the final product.

SUSVIMO (ranibizumab injection) is supplied as a sterile, clear to slightly opalescent, colorless to pale brown solution for intravitreal use via the SUSVIMO implant. Each single-dose vial contains 10 mg of ranibizumab, histidine HCl (0.1 mg), polysorbate 20 (0.01 mg), sucrose (8.2 mg), and Water for Injection, in 0.1 mL of solution with a pH of 5.5. The SUSVIMO implant is designed to contain approximately 0.02 mL (2 mg) of ranibizumab solution when filled. SUSVIMO does not contain an antimicrobial preservative.

12 CLINICAL PHARMACOLOGY

13 NONCLINICAL TOXICOLOGY

14 CLINICAL STUDIES

The clinical efficacy and safety of SUSVIMO (ranibizumab injection) was assessed in a randomized, visual assessor-masked, active treatment-controlled study (Archway-NCT03677934) in patients with AMD. A total of 415 patients (248 in the SUSVIMO arm and 167 in the intravitreal ranibizumab arm) were enrolled and treated in this study. Patients were diagnosed with nAMD within the 9 months prior to screening and received ≥ 3 doses of anti-VEGF intravitreal agents in the study eye within the last 6 months prior to screening. Each patient was required to have demonstrated a response to an anti-VEGF intravitreal agent prior to randomization. Patients were randomized in a 3:2 ratio to receive continuous delivery of SUSVIMO (ranibizumab injection) via the SUSVIMO implant every 24 weeks or 0.5 mg intravitreal ranibizumab injections every 4 weeks. For patients randomized to the SUSVIMO arm, supplemental treatment with 0.5 mg intravitreal ranibizumab injections was available at Weeks 16, 20, 40, 44, 64, 68, 88, and 92, if needed. In the first 24 weeks, 1.6% of patients assessed for supplemental treatment received 1 or more supplemental treatment(s) and in the following 24 weeks, 5.4% of patients assessed for supplemental treatment received 1 or more supplemental treatment(s).

The primary efficacy endpoint of change from baseline in distance Best Corrected Visual Acuity (BCVA) score averaged over Week 36 and Week 40 demonstrated that SUSVIMO was equivalent to intravitreal ranibizumab injections administered every 4 weeks. Detailed efficacy results are shown in Table 3 and Figure 29 below.

Consistent results were observed across patient subgroup analyses for mean change from baseline in BCVA score (age, gender, number of prior anti-VEGF intravitreal injections, and baseline BCVA score).

16 HOW SUPPLIED/STORAGE AND HANDLING

16.1 How Supplied

Each SUSVIMO initial fill needle kit (NDC 50242-078-55) contains:

• One SUSVIMO 100 mg/mL single-dose glass vial
• One SUSVIMO initial fill needle (34-gauge needle with a 5 μm integrated filter) with a blue cap

Each SUSVIMO (ranibizumab injection) carton (NDC 50242-078-12) contains one SUSVIMO (ranibizumab injection) 100 mg/mL that is clear to slightly opalescent, colorless to pale brown solution in a single-dose glass vial.

Each SUSVIMO refill needle carton contains a SUSVIMO refill needle (34-gauge vented needle with a 5 μm integrated filter) with a clear cap.

Device and Materials Description
Components
Figure 30
SUSVIMO implant SUSVIMO implant (Figure 31) is capable of holding 0.02 mL of drug, and is secured within the sclera, by the extrascleral flange that remains visible through the conjunctiva following insertion. The septum is a self-sealing interface through which ranibizumab is administered to fill the implant.	Figure 31
SUSVIMO (ranibizumab injection) 100 mg/mL vial SUSVIMO (ranibizumab injection) (Figure 32) is used to fill the implant with ranibizumab prior to insertion or during subsequent refill-exchange in an office-based setting.	Figure 32
SUSVIMO refill needle SUSVIMO refill needle (Figure 33) consists of a 34 G vented needle assembly, silicone soft stop, and a 5 μm integrated filter within the needle hub. It is designed to simultaneously exchange the contents of the implant reservoir with replacement ranibizumab in an office-based setting. As replacement ranibizumab is administered into the implant through the stainless-steel cannula, fluid remaining in the implant flows through openings in the vented needle and is collected in the fluid collection reservoir. SUSVIMO refill needle is distinguished by its clear cap.	Figure 33

Materials List

Materials that are required and supplied to perform the procedure are:

• SUSVIMO refill needle, 34 G, with clear cap
• SUSVIMO (ranibizumab injection) 100 mg/mL

Additional materials required to perform the procedure but are not provided are:

• One sterile 1 mL Luer Lock syringe (not included)
• One sterile 5-micron filter needle (19-gauge × 1½ inch) (not included)
• Anesthetic ophthalmic solutions
• Ophthalmic broad-spectrum microbicide solution
• Cotton tips and gauze
• Sterile powder free gloves
• Face masks
• Lid speculum
• Magnification such as visor or loupes
• Task lighting
• Indirect ophthalmoscope and lens
• Sterile drape (optional for refill-exchange procedure)

17 PATIENT COUNSELING INFORMATION

Advise the patient to read the FDA-approved patient labeling (Medication Guide).

SUSVIMO™ [ranibizumab injection]
Manufactured by:
Genentech, Inc.
A Member of the Roche Group
1 DNA Way
South San Francisco, CA 94080-4990
U.S. License No.: 1048

SUSVIMO is a trademark of Genentech, Inc.
©2021 Genentech, Inc.

Susvimo™
(ranibizumab injection)
For Susvimo ocular implant use
Instructions for Use

Caution: Federal Law (USA) restricts this device to sale by or on the order of a physician.

Susvimo procedures should be performed by an ophthalmologist experienced in vitreoretinal surgery.

Refer to the Susvimo (ranibizumab injection) 100 mg/mL prescribing information for a complete list of indications, contraindications, warnings, precautions, and adverse events.

Contents

Introduction

Instructions for Use

Introduction

These instructions include only the procedure for filling and inserting the Susvimo implant. For more information, refer to the Susvimo prescribing information for the refill-exchange procedure and Susvimo Instructions for Use for the implant removal procedure.

Device Description

Susvimo is an intraocular drug delivery system designed to be used specifically with Susvimo (ranibizumab injection) 100 mg/mL. The system consists of an intraocular implant along with ancillary devices used to fill, insert, and explant (if needed) the implant.

The implant is a refillable drug reservoir that is inserted into the eye through the pars plana. The implant is secured within the scleral incision, with the extrascleral flange that remains visible through the conjunctiva following insertion. Once filled with ranibizumab, the implant is designed to provide continuous release of ranibizumab. The implant will be refilled with ranibizumab in an office-based setting via an administration through the conjunctiva and implant septum.

Components

Figure 1

Susvimo components for initial fill and implant procedure

Susvimo implant (packaged with insertion tool assembly)

Susvimo implant (Figure 2 and Figure 3) is a refillable reservoir inserted into the eye through the pars plana. The body of the implant, which includes the release control element, extends into the vitreous cavity.

Susvimo insertion tool assembly

Susvimo insertion tool assembly is designed to facilitate handling of the implant during the initial fill and implant procedure. The insertion tool assembly is comprised of a carrier and handle (Figure 4 and Figure 5), described in more detail below:

Susvimo (ranibizumab injection) 100 mg/mL vial

Susvimo (ranibizumab injection) (Figure 6) is used to fill the implant prior to insertion or during subsequent refill-exchange in an office-based setting.

Figure 6
Susvimo (ranibizumab injection) 100 mg/mL vial

Susvimo initial fill needle

Susvimo initial fill needle (Figure 7) is designed to fill the implant with ranibizumab prior to implant insertion. The initial fill needle is distinguished by its blue cap.

Figure 7
Susvimo initial fill needle

Intended Use/Indications for Use

Susvimo ocular implant is approved for use with Susvimo (ranibizumab injection). Refer to the Susvimo (ranibizumab injection) prescribing information for a complete list of indications, contraindications, warnings, precautions, and adverse events.

Contraindications

Susvimo is contraindicated in patients with ocular or periocular infections, with active intraocular inflammation, or with known hypersensitivity to ranibizumab or any of the excipients in Susvimo (ranibizumab injection) 100 mg/mL. Hypersensitivity reactions may manifest as severe intraocular inflammation.

Warnings

• Do not use if the sterility has been compromised or the contents have been dropped, damaged or tampered with.
• Minimize air bubbles within the implant reservoir as they may cause slower drug release. If an air bubble is present, it must be no larger than 1/3 of the widest diameter of the implant.
  If excess air is observed after initial fill, do not use the implant.
• Perpendicular entry of the implant is important to avoid contact between the implant and intraocular structures such as the lens, as contact between the implant and the intraocular structures may cause adverse events such as traumatic cataract.
• Avoid excessive force on the globe by first ensuring that the tip of the implant has passed through the sclero-pars plana incision before slowly pushing the implant into place.

Precautions

• Read and follow all instructions, warnings, and cautions prior to use.
• Susvimo procedures should be performed by an ophthalmologist experienced in vitreoretinal surgery.
• Use the Susvimo components and materials as specified in these instructions to perform the implant insertion procedure including initial fill.
• Avoid contact between sharp surgical instruments and the implant as the material of the septum and silicone encasing are soft and susceptible to damage.
• The implant is MR Conditional. The Patient Implant card is provided with instructions and must be completed and given to the patient after implant insertion. For further information please refer to the 'Post-insertion patient instructions' section.

Use with Standard Procedures

Susvimo implant is compatible for use with the following standard procedures: A-scan ophthalmic ultrasound, slit lamp examination, indirect ophthalmoscopy, tonometry, optical coherence tomography (OCT), visual field (perimetry), standard lasers for ophthalmic treatments, radiography (x-ray), computed tomography (CT) scan, fluorescein/ indocyanine angiography, and fundus autofluorescence.

Use caution when performing ophthalmic procedures that may cause deflection of the implant and subsequent injury. For example, B-scan ophthalmic ultrasound, scleral depression, or gonioscopy.

Magnetic Resonance Imaging (MRI) Safety Information

MR Conditional.

Non-clinical testing has demonstrated that the Susvimo implant is MR Conditional. A patient with this device can be safely scanned in an MR system meeting the following conditions:

• Static magnetic field of 1.5-Tesla (1.5 T) or 3-Tesla (3 T)
• Maximum spatial field gradient of 3,000 G/cm (30 T/m)
• Maximum MR system reported, whole body averaged specific absorption rate (SAR) of 4.0 W/kg (First Level Controlled Operating Mode)

Under the scan conditions defined above, the Susvimo implant is expected to produce a maximum temperature rise of less than 1°C after 15 minutes of continuous scanning.

In non-clinical testing, the image artifact caused by the device extends approximately 4 mm from the Susvimo implant when imaged with a gradient echo pulse sequence in a 3 T MRI system.

How Supplied, Handling, and Storage

• All Susvimo components are supplied sterile.
  Do not reprocess or resterilize.
• All Susvimo components are for single use only.
  Do not reuse Susvimo components.
• Do not open sealed tray until time of use.
• Do not use if the package is damaged or broken as sterility may be compromised.
• Do not use past the expiration date printed on the label.

Susvimo ocular implant and insertion tool assembly

• The sealed tray has been sterilized with ethylene oxide gas.
• Store the Susvimo implant and insertion tool assembly at room temperature 15°C to 25°C (59°F to 77°F).

Susvimo (ranibizumab injection) and initial fill needle kit

• Susvimo initial fill kit should be stored at 2°C to 8°C (36°F to 46°F). Do not freeze. Protect from light. Do not shake. Prior to use, the unopened vial may be kept at 9°C to 30°C (48°F to 86°F) for up to 24 hours.
• Susvimo initial fill needle has been sterilized with electron beam processing.

See Susvimo (ranibizumab injection) prescribing information for additional information.

Instructions for Use

Introduction and Materials

Implant insertion is a surgical procedure that is performed in an operating room. The implant is filled with Susvimo (ranibizumab injection) immediately prior to insertion.

Materials List

The materials that are required in the operating room on the day of the procedure are listed in Tables 4 and 5.

Preparatory Procedures

Infusion Line Placement Procedure

Conjunctival Dissection Procedure

Syringe Preparation and Initial Implant Fill

Using aseptic technique, the implant will be filled with 0.02 mL of ranibizumab prior to insertion of the implant into the patient's eye.

Implant Insertion

1. Verify hemostasis of the scleral surface

• Clear any excess blood from the scleral surface.
• Perform careful scleral wet field cauterization as needed, particularly in the area of the sclero-pars plana incision.

• Using a 532 nm laser endoprobe, apply contiguous, overlapping laser spots starting at 300 mW 1000 ms along the full length of the exposed pars plana (Figure 32). Repeat until complete ablation is achieved.

  –

  Maintain focus of laser on exposed pars plana.

  –

  Keep foot pedal depressed to achieve full 1000 ms spots (expect smoke).

  –

  Ensure the pars plana at the corners of scleral incision is adequately treated.

  –

  Do not use painting strokes with the laser.

  –

  Do not contact the pars plana directly with laser probe.

• Repeat application of laser along the full length of the pars plana until full or partial split of the pars plana, or other visual endpoints are achieved, as indicated by:

  –

  Gray color change.

  –

  Uniform perforated appearance.

  –

  Domes of vitreous fluid percolating through pars plana.

• If visual endpoint is not achieved after several passes with the laser, increase laser power in 100 mW increments.
• Once laser ablation of pars plana is completed, remeasure the entire length (including corners) of the scleral incision with 3.5 mm gauge to confirm the final post-laser incision is 3.5 mm. If final incision is greater than 3.5 mm, as indicated by a loose fit/side to side motion of 3.5 mm gauge, place a suture through the wound opposite the relaxing incision to reduce incision down to 3.5 mm.

Caution

A final post-laser incision length of 3.5 mm provides a secure fit for the implant.

Do not enlarge the scleral dissection beyond 3.5 mm as a final incision length greater than 3.5 mm may result in an improperly seated implant and will require additional suturing.

13. Remove infusion cannula

• If the infusion was previously turned on, then set the infusion pressure to 20 mmHg before removing the infusion cannula.
• Check for persistent leaks at the infusion cannula site and suture if necessary.

14. Check Intraocular Pressure (IOP)

• Using digital palpation, check the IOP. If necessary, inject additional fluid to restore IOP.

15. Check implant placement

• Perform indirect ophthalmoscopy to confirm implant position and to examine for the presence of any complications.

Disposal and Post-insertion Procedures

1. Dispose of used Susvimo components and tools

• Do not recap the needle or detach it from the syringe. Dispose of the used Susvimo components and tools in a sharps disposal container or in accordance with local requirements.

2. Perform post-insertion procedures

• Post-insertion procedures are consistent with standard post-surgical procedures.

3. Post-insertion patient instructions

Provide the patient with the following post-operative instructions:

• Positioning:

  –

  Keep head above shoulder level for the rest of the day.

  –

  Sleep with head elevated on 3 or more pillows if lying down during the day and night after implant insertion.

• Information on caring for the eye after the procedure, including but not limited to the following:

  –

  Do not remove the eye shield until they are instructed to do so by their physician. At bedtime, continue to wear the eye shield for at least 7 nights following implant insertion.

  –

  Administer all post-operative eye medications, as directed by their physician.

  –

  Do not push on the eye, rub the eye, or touch the region of the eye where the implant is located (underneath the eyelid in the upper and outer part of the eye) for 30 days following implant insertion. Avoid rubbing the eye or touching the area where the implant is located as much as possible at all other times but if necessary to do so, make sure hands are cleaned prior to touching the eye.

  –

  Do not participate in strenuous activities until 1 month after implant insertion or after discussion with their physician.

• Monitor for symptoms that may require immediate medical attention while the implant is in place.
• MR Conditional information:

  –

  The surgeon should inform the patient that the implant is MR Conditional (as noted on their Susvimo implant card) and if patient needs to undergo an MRI, they should let their doctor know they have Susvimo implanted in their eye.

  –

  After implant insertion, the surgeon should give the patient the implant card (enclosed in this IFU on the last page) with the appropriate information filled in, and should advise the patient to keep the card in a safe place, e.g. his or her wallet, for future reference. The surgeon should advise the patient that this implant card contains important information related to the Susvimo implant and that the card should be shown to their current and future health care providers.

Explanation of symbols on product or package labeling

Table 6 Symbols on blister tray and carton

Symbol	Title
	Manufacturer
	Prescription only
	Do not re-use
	Do not use if package is damaged
	Consult Instructions for Use
	Sterilized by irradiation
	Sterilized using ethylene oxide
	Temperature limit
	Expiration date/Use by date
	Lot/Batch number
	MR Conditional

Manufactured by:

Genentech, Inc.
A Member of the Roche Group
1 DNA Way
South San Francisco, CA 94080-4990
U.S. License No.: 1048

SUSVIMO is a trademark of Genentech, Inc.
©2021 Genentech, Inc. All rights reserved.

This Instructions for Use has been approved by the U.S. Food and Drug Administration.
Approved: 4/2022

Susvimo™
(ranibizumab injection)
For Susvimo ocular implant use
Instructions for Use

Caution: Federal Law (USA) restricts this device to sale by or on the order of a physician.

Susvimo procedures should be performed by an ophthalmologist experienced in vitreoretinal surgery.

Refer to the Susvimo (ranibizumab injection) 100 mg/mL prescribing information for a complete list of indications, contraindications, warnings, precautions, and adverse events.

Contents

Introduction

Instructions for Use

Introduction

These instructions include only the implant removal procedure for the Susvimo implant. Refer to the Susvimo Instructions for Use for the initial fill and implant procedure and prescribing information for the refill-exchange procedure.

Device Description

Susvimo is an intraocular drug delivery system designed to be used specifically with Susvimo (ranibizumab injection) 100 mg/mL.

These Instructions for Use describe the required materials and steps necessary for removal of the Susvimo implant.

Components

Figure 1 Susvimo components for implant removal procedure

Susvimo explant tool

Susvimo explant tool (Figure 2) is a pair of forceps with contoured tips, which are designed to grasp underneath the implant flange to securely engage the implant during removal.

Figure 2 Susvimo explant tool

Intended Use/ Indications for Use

Susvimo explant tool is approved for use with Susvimo ocular implant. Refer to the Susvimo (ranibizumab injection) prescribing information for a complete list of indications, contraindications, warnings, precautions, and adverse events.

Warnings

• Do not use if the sterility has been compromised or the contents have been dropped, damaged or tampered with.
• Do not grasp the implant by the short axis of the implant flange. Remove the implant in a gentle manner. Perpendicular exit of the implant is important to avoid contact between the implant and intraocular structures such as the lens.

Precautions

• Read and follow all instructions, warnings, and cautions prior to use.
• Susvimo procedures should be performed by an ophthalmologist experienced in vitreoretinal surgery.
• Use Susvimo components and materials as specified in these instructions to perform the implant removal procedure.

How Supplied, Handling, and Storage

• Susvimo explant tool has been electron beam sterilized. Do not reprocess or resterilize.
• Susvimo explant tool is for single-use only. Do not reuse the Susvimo explant tool.
• Do not open sealed tray until time of use.
• Do not use if the package is damaged or broken as sterility may be compromised.
• Do not use past the expiration date printed on the label.
• Susvimo explant tool should be stored at a room temperature 15°C to 25°C (59°F to 77°F).

Instructions for Use

Introduction and Materials

Removal of the Susvimo implant requires a surgical procedure that is performed in an operating room.

Materials List

Materials that are required and provided for the procedure are listed in Table 1.

Materials required but not provided are listed in Table 2.

Preparatory Procedures

1. Inspect and open sterile packaging

• Prior to use in the operating room, inspect the sterile packaging of the explant tool for damage.
• Check the expiration date printed on the label.
• Open sterile packaging and using aseptic technique, remove the explant tool from the tray.
• Inspect the explant tool and place onto sterile surface.

Warning

Do not use if the sterility has been compromised or the contents have been dropped, damaged, or tampered with.

2. Patient Preparation

• Dilate the pupil of the eye.
• Place the patient in a supine position on the operating table.
• Implant removal is a surgical procedure and therefore requires sterile controls (i.e. use of ophthalmic broad-spectrum microbicide solution on eye including lids and lashes and draping) be in place to minimize the risk of ocular infection.
• Perform the procedure under local anesthesia using either peribulbar, retrobulbar, or sub-Tenon's technique.
• Place lid speculum.

Implant Removal

Perform the implant removal procedure under the microscope. Consider placing a traction suture for better visualization of the superotemporal quadrant throughout the entire implant removal procedure.

1. Place infusion line

• Place an infusion cannula in the inferotemporal quadrant via an angled entry wound.
• Attach the infusion line, however keep the infusion off.

2. Perform conjunctival peritomy

• Create at least a 6 mm by 6 mm peritomy of the conjunctiva and Tenon's capsule around the implant flange (Figure 3).

Figure 3 Conjunctival peritomy

3. Remove fibrous capsule covering implant

• Remove any fibrous capsule or scar tissue that may have formed over the implant flange and septum (Figure 4 and Figure 5).

  –

  To expose the implant, use a scalpel to make an incision in the tissue around the entire circumference of the implant (Figure 4).

  –

  Use forceps to carefully dissect the implant flange and neck from the surrounding tissue so that the edges of the flange are completely exposed and the implant is free of any adherent tissue (Figure 5).

Figure 4 Incision to remove tissue that may be covering the implant flange and septum

Figure 5 Exposed implant

4. Stabilize the globe and align the explant tool

• Stabilize the globe with forceps to prevent unwanted eye movement.
• With the explant tool oriented perpendicular to the globe, align the contoured tips with the long axis of the implant flange (Figure 6).

Figure 6 Align the explant tool along the long axis of the implant flange

5. Grasp the implant

Warning

Do not grasp the implant by the short axis of the implant flange. Remove the implant in a gentle manner. Perpendicular exit of the implant is important to avoid contact between the implant and intraocular structures such as the lens.

• Use the contoured tips of the explant tool to gently grasp underneath the long axis of the implant flange (Figure 7).

Figure 7 Grasp underneath the long axis of the implant flange

6. Remove the implant

• Once the implant is secured in the explant tool, in a gentle manner pull the implant from the eye in a perpendicular motion to avoid contact with adjacent intraocular structures.
• During removal, use forceps to stabilize the globe and provide counter traction to help release the surrounding tissue (Figure 8).
• During removal, continue to maintain perpendicular orientation of the implant relative to the globe (Figure 9).

  Figure 8 Implant removal

  Figure 9 Perpendicular exit of the implant

• If needed per the surgeon's discretion, the infusion line on the vitrectomy surgical system can be turned on during implant removal.
• Control any scleral or conjunctival bleeding, using cauterization if needed, and clear any vitreous prolapse present within or around the scleral wound using a vitrectomy setup.

  Figure 10 Appearance of the scleral wound after implant removal

7. Suture the sclera

• Completely close the scleral incision with non-absorbable (suggested Nylon) sutures (Figure 11). More than one suture will be needed to close the wound. It is recommended to place equally spaced partial thickness interrupted sutures.
• Ensure that the knots are buried.

Caution

Do not overtighten the scleral sutures, to minimize excessive tensions on the sclera or cornea.

Figure 11 Suture scleral wound using multiple sutures

8. Suture conjunctiva

• Close Tenon's capsule and conjunctiva to completely cover the scleral incision (Figure 12).

Caution

Completely close Tenon's capsule and conjunctiva to minimize potential post-removal complications.

Figure 12 Suture conjunctiva post-removal

9. Remove infusion cannula

• If the infusion was previously turned on, then set the infusion pressure to 20 mmHg before removing the infusion cannula.
• Place suture at infusion cannula site as needed.

10. Check Intraocular Pressure (IOP) using digital palpation

11. Perform indirect ophthalmoscopy to examine for the presence of any complications

Disposal and Post-removal Procedures

1. Dispose of the used components

• Dispose of the used explant tool together with the implant in a biohazard waste container or in accordance with local requirements.

2. Perform post-removal procedures

• Post-removal procedures are consistent with standard post-surgical procedures.

3. Post-removal patient instructions

• Provide the patient with the following post-operative instructions:

  –

  Positioning:

  • Keep head above shoulder level for the rest of the day.
  • Sleep with head elevated on 3 or more pillows if lying down during the day and night after implant removal.

  –

  Information on caring for the eye after the procedure, including but not limited to:

  • Monitor for symptoms that may require immediate attention.
  • Wear an eye shield at bedtime for at least 7 nights.
  • Do not participate in strenuous activities until 14 days following the implant removal procedure.
  • Administer all post-operative anti-inflammatory and antimicrobial drops, as directed by their physician.

Explanation of symbols on product or package labeling

Table 3 Symbols on blister tray and carton

Symbol	Title
	Manufacturer
	Prescription only
	Do not re-use
	Do not use if package is damaged
	Consult Instructions for Use
	Sterilized by irradiation
	Temperature limit
	Expiration date/ Use by date
	Lot/Batch number

Manufactured by:
Genentech, Inc.
A Member of the Roche Group
1 DNA Way
South San Francisco, CA 94080-4990

U.S. License No.: 1048

SUSVIMO is a trademark of Genentech, Inc.
©2021 Genentech, Inc.
All rights reserved.

This Instructions for Use has been approved by the U.S. Food and Drug Administration.

Approved: 10/2021

Representative sample of labeling (see the HOW SUPPLIED section for complete listing):

PRINCIPAL DISPLAY PANEL - Kit Carton

NDC 50242-078-55

Susvimo™
(ranibizumab injection)

See instructions for use
included with the
Susvimo ocular implant
with insertion tool assembly

100 mg/mL

Vial contains 10 mg/0.1 mL ranibizumab

For use with Susvimo ocular implant

Dispense the enclosed Medication Guide to each patient.

Carton contents:

• One Susvimo single-dose vial
• One Susvimo initial fill needle

Rx only

Genentech

10233586

PRINCIPAL DISPLAY PANEL - 10 mg/0.1 mL Vial Carton

NDC 50242-078-12

Susvimo™
(ranibizumab injection)

100 mg/mL

Vial contains
10 mg/0.1 mL ranibizumab

For use with Susvimo
ocular implant

Dispense the enclosed
Medication Guide to each patient.

Rx only

1 Single-dose vial

Genentech

10233583