Susvimo

SUSVIMO (ranibizumab injection) is a vascular endothelial growth factor (VEGF) inhibitor 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 VEGF inhibitor (
  1.1 Neovascular (wet) Age-related Macular Degeneration (AMD)

  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.
  ).
• Diabetic Macular Edema (DME) who have previously responded to at least two intravitreal injections of a VEGF inhibitor (
  1.2 Diabetic Macular Edema (DME)

  SUSVIMO (ranibizumab injection) is indicated for the treatment of patients with Diabetic Macular Edema (DME) who have previously responded to at least two intravitreal injections of a Vascular Endothelial Growth Factor (VEGF) inhibitor medication.
  ).
• Diabetic Retinopathy (DR) who have previously responded to at least two intravitreal injections of a VEGF inhibitor (
  1.3 Diabetic Retinopathy (DR)

  SUSVIMO (ranibizumab injection) is indicated for the treatment of patients with Diabetic Retinopathy (DR) who have previously responded to at least two intravitreal injections of a Vascular Endothelial Growth Factor (VEGF) inhibitor medication.
  ).

• For intravitreal use via SUSVIMO ocular implant. (
  2.1 General Information

  For Intravitreal Use via SUSVIMO ocular implant.

  The SUSVIMO initial fill and ocular implant insertion and implant removal procedures must be performed under aseptic conditions by a physician experienced in vitreoretinal surgery. The SUSVIMO ocular implant must be surgically implanted in the eye or removed from the eye (if medically necessary) in an operating room using aseptic technique. See SUSVIMO Instructions for Use and the standardized steps to optimize surgical outcomes.

  SUSVIMO refill-exchange procedures must be performed under aseptic conditions by a physician experienced in ophthalmic surgery

  [see Dosage and Administration (2.7)]

  .

  Do not administer SUSVIMO (ranibizumab injection) as a bolus intravitreal injection. Do not substitute SUSVIMO (ranibizumab injection) with other ranibizumab products.

  Initial Fill

  : One SUSVIMO initial fill needle (34-gauge, with integrated 5 μm filter and blue cap) is included. A 5-micron sterile filter needle (19-gauge × 1½ inch), and a 1 mL Luer lock syringe are needed but

  not included

  .

  Refill-Exchange

  : One SUSVIMO refill needle (34-gauge with integrated 5 μm filter and clear cap) is included. A 5-micron sterile filter needle (19-gauge × 1½ inch), and a 1 mL Luer lock syringe are needed but

  not included

  .
  )
• Neovascular (wet) Age-related Macular Degeneration (AMD) and Diabetic Macular Edema (DME)
  
  
  The recommended dose of SUSVIMO (ranibizumab injection) is 2 mg (0.02 mL of 100 mg/mL solution) continuously delivered via the SUSVIMO implant with refills every 24 weeks (approximately 6 months). (
  2.2 Neovascular (Wet) Age-Related Macular Degeneration (AMD) and Diabetic Macular Edema (DME)

  The recommended dose of SUSVIMO (ranibizumab injection) is 2 mg (0.02 mL of 100 mg/mL solution) continuously delivered via the SUSVIMO ocular implant with refills administered every 24 weeks (approximately 6 months).
  )
• Diabetic Retinopathy (DR)
  
  
  The recommended dose of SUSVIMO (ranibizumab injection) is 2 mg (0.02 mL of 100 mg/mL solution) continuously delivered via the SUSVIMO implant with refills every 36 weeks (approximately 9 months). (
  2.3 Diabetic Retinopathy (DR)

  The recommended dose of SUSVIMO (ranibizumab injection) is 2 mg (0.02 mL of 100 mg/mL solution) continuously delivered via the SUSVIMO ocular implant with refills administered every 36 weeks (approximately 9 months).
  )
• Supplemental treatment with 0.5 mg intravitreal ranibizumab injection may be administered in the affected eye if clinically necessary. (
  2.4 Supplemental Treatment with Intravitreal Ranibizumab Injection

  Supplemental treatment with 0.5 mg (0.05 mL of 10 mg/mL) intravitreal ranibizumab injection may be administered in the affected eye while the SUSVIMO implant is in place and if clinically necessary

  [see Clinical Studies (14)]

  .
  )
• Perform the initial implantation, refill-exchange, and implant removal (if necessary) procedures under strict aseptic conditions. (
  2.5 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 (2.6)].

  Refer to the complete SUSVIMO Instructions for Usefor 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:

  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.

  –

  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.
  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.

  

  

  

  

  

  

  

  

  

  

  

  

  

  

  

  ,
  2.6 Ocular Implant Insertion

  SUSVIMO ocular implant insertion is a surgical procedure that is performed in an operating room. The procedure must be performed under aseptic conditions by a physician experienced in vitreoretinal surgery

  [see Dosage and Administration (2.1)]

  .

  The ocular implant is filled with SUSVIMO (ranibizumab injection) immediately prior to insertion.

  No more than 30 minutes should pass between the initial fill of the ocular implant and the insertion into the patient's eye.

  After placing an infusion line in the eye, create at least a 6×6 mm peritomy of the conjunctiva and Tenon's capsule centered around the selected SUSVIMO implant location in the supero-temporal quadrant. Perform careful conjunctival incision, hemostasis of the underlying sclera, and generous undermining of Tenon's capsule. Using aseptic technique, fill the ocular implant

  [see Dosage and Administration (2.5)]

  . Using an MVR blade, create a full thickness dissection of the sclera 4 mm from the limbus until the pars plana is fully visible, with final target scleral incision length of 3.5 mm. 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 and repeat until complete ablation is achieved. Pass a 3.2 mm slit knife perpendicularly through the center of the scleral dissection to open the underlying pars plana. Use the insertion tool to slowly insert the SUSVIMO implant into the sclero-pars plana incision perpendicular to the globe, ensuring that the long axis of the implant flange is properly aligned with the sclero-pars plana incision. Using the closed gripper tips of the insertion tool, seat the implant flush against the sclera. Clean any residual vitreous around the implant flange using a vitrector. Suture both Tenon's capsule and conjunctiva, using scleral anchoring at the apex of the peritomy, ensuring complete coverage of the implant flange. Refer to the complete SUSVIMO Instructions for Usefor the initial fill and implant procedure included in the insertion tool assembly carton for further details.
  ,
  2.7 Ocular Implant Removal

  Removal of the SUSVIMO ocular implant is a surgical procedure that is performed in an operating room. The procedure must be performed under aseptic conditions by a physician experienced in vitreoretinal surgery

  [see Dosage and Administration (2.1)]

  .

  After placing an infusion line in the eye, create at least a 6×6 mm peritomy of the conjunctiva and Tenon's capsule around the SUSVIMO ocular implant flange. Remove any fibrous capsule or scar tissue that may have formed over the implant flange and septum using scalpel and forceps. With the explant tool oriented perpendicular to the globe, align the contoured tips with the long axis of the implant flange and grasp underneath the implant flange. Once the implant is secured in the explant tool, pull the implant from the eye in a perpendicular motion. Clear any vitreous prolapse present within or around the scleral wound using a vitrector. Completely close the scleral incision with multiple non-absorbable sutures. Close the Tenon's capsule and conjunctiva to completely cover the scleral incision. Refer to the complete Instructions for Usefor the implant removal procedure included in the explant tool carton for further details.
  ,
  2.8 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 33and 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.

  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.

  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).

  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 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 slightly brownish 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.
  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 23 Figure 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).
  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).
  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.

  

  

  

  

  

  

  

  

  

  

  

  

  

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

There are no adequate and well-controlled studies of SUSVIMO (ranibizumab injection) administration in pregnant women. Administration of ranibizumab to pregnant monkeys throughout the period of organogenesis resulted in a low incidence of skeletal abnormalities at intravitreal doses up to 41 times the human exposure (based on serum levels following the recommended clinical dose). No skeletal abnormalities were observed at serum trough levels similar to the human exposure after a single eye treatment at the recommended clinical dose (

Animal reproduction studies are not always predictive of human response, and it is not known whether ranibizumab can cause fetal harm when administered to a pregnant woman. Based on the anti-VEGF mechanism of action for ranibizumab

All pregnancies have a background risk of birth defects, loss, and other adverse outcomes. The background risk of major birth defects and miscarriage for the indicated population is unknown. In the U.S. general population, the estimated background risk of major birth defects is 2% – 4% and of miscarriage is 15% – 20% of clinically recognized pregnancies.