BLA 761197
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`Page 8
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`HIGHLIGHTS OF PRESCRIBING INFORMATION
`
`These highlights do not include all the information needed to use
`
`SUSVIMO safely and effectively. See full prescribing information for
`
`SUSVIMO.
`
`
`
`
`
`
`
`SUSVIMOTM (ranibizumab injection) for intravitreal use via SUSVIMO
`
`ocular implant
`
`Initial U.S. Approval: 2006
`
`
`
`
`
`
`WARNING: ENDOPHTHALMITIS
`See full prescribing information for complete boxed warning.
`
`The SUSVIMO implant has been associated with a 3-fold higher rate of
`endophthalmitis than monthly intravitreal injections of ranibizumab. In
`clinical trials, 2.0% of patients receiving an implant experienced an
`episode of endophthalmitis.
`
`----------------------------INDICATIONS AND USAGE--------------------------­
`
`SUSVIMO (ranibizumab injection), a vascular endothelial growth factor
`
`(VEGF) inhibitor, 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 VEGF inhibitor (1.0).
`
`
`-----------------------DOSAGE AND ADMINISTRATION---------------------­
`
`For intravitreal use via SUSVIMO ocular implant. (2.1)
`
`
`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)
`Supplemental treatment with 0.5 mg intravitreal ranibizumab injection
`may be administered in the affected eye if clinically necessary. (2.3)
`Perform the initial implantation, refill-exchange, and implant removal (if
`necessary) procedures under strict aseptic conditions. (2.4, 2.5, 2.6, 2.7)
`
`
`
`
`
`
`
`-------------------------DOSAGE FORMS AND STRENGTHS-----------------­
`Injection: 100 mg/mL solution in a single-dose vial (3)
`
`
`
`
`---------------------------------CONTRAINDICATIONS--------------------------­
`
`Ocular or periocular infections (4.1)
`
`
`Active intraocular inflammation (4.2)
`
`
`Hypersensitivity (4.3)
`
`
`
`---------------------------WARNINGS AND PRECAUTIONS-------------------­
`
`The SUSVIMO implant and/or implant-related procedures have been
`
`
`associated with endophthalmitis, rhegmatogenous retinal detachment,
`implant dislocation, vitreous hemorrhage, conjunctival retraction,
`conjunctival erosion, and conjunctival bleb. Patients should be instructed to
`report signs or symptoms that could be associated with these events without
`
`
`delay. Additional surgical and/or medical management may be required.
`
`(5.1, 5.2, 5.3, 5.4, 5.5, 5.6)
`Vitreous Hemorrhage: Temporarily discontinue antithrombotic medication
`prior to the implant insertion procedure to reduce the risk of vitreous
`hemorrhage. Vitrectomy may be needed. (5.4)
`Postoperative Decrease in Visual Acuity: A decrease in visual acuity usually
`occurs over the first two postoperative months. (5.7)
`
`
`
`
`
`
`
`---------------------------------ADVERSE REACTIONS--------------------------­
`
`The most common adverse reactions were conjunctival hemorrhage (72%),
`
`conjunctival hyperemia (26%), iritis (23%) and eye pain (10%) (6.1)
`
`
`To report SUSPECTED ADVERSE REACTIONS, contact Genentech at 1­
`
`888-835-2555 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.
`
`
`See 17 for PATIENT COUNSELING INFORMATION and Medication
`
`Guide.
`
`
`Revised: 10/2021
`
`
`
`FULL PRESCRIBING INFORMATION: CONTENTS*
`
`WARNING: ENDOPHTHALMITIS
`1
`INDICATIONS AND USAGE
`2
`DOSAGE AND ADMINISTRATION
`2.1 General Information
`2.2 Neovascular (Wet) Age-Related Macular Degeneration (AMD)
`2.3 Supplemental Treatment with Intravitreal Ranibizumab Injection
`2.4 Ocular Implant Initial Fill
`2.5 Ocular Implant Insertion
`2.6 Ocular Implant Removal
`2.7 Ocular Implant Refill-Exchange Procedure
`2.8 Delayed or Missed doses
`2.9 Dosage (Refill-Exchange) Modifications for Adverse Reactions
`DOSAGE FORMS AND STRENGTHS
`CONTRAINDICATIONS
`4.1 Ocular or Periocular Infections
`4.2 Active Intraocular Inflammation
`4.3 Hypersensitivity
`5 WARNINGS AND PRECAUTIONS
`5.1 Endophthalmitis
`5.2 Rhegmatogenous Retinal Detachment
`5.3 Implant Dislocation
`5.4 Vitreous Hemorrhage
`5.5 Conjunctival Erosion or Retraction
`
`3
`4
`
`
`
`Reference ID: 4876896
`
`6
`
`8
`
`5.6 Conjunctival Bleb
`5.7 Postoperative Decrease in Visual Acuity
`5.8 Air Bubbles Causing Improper Filling of the Implant
`5.9 Deflection of Implant
`ADVERSE REACTIONS
`6.1 Clinical Trials Experience
`6.2 Immunogenicity
`USE IN SPECIFIC POPULATIONS
`8.1 Pregnancy
`8.2 Lactation
`8.3 Females and Males of Reproductive Potential
`8.4 Pediatric Use
`8.5 Geriatric Use
`DESCRIPTION
`CLINICAL PHARMACOLOGY
`12.1 Mechanism of Action
`12.3 Pharmacokinetics
`13 NONCLINICAL TOXICOLOGY
`13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility
`CLINICAL STUDIES
`HOW SUPPLIED/STORAGE AND HANDLING
`16.1 How Supplied
`16.2 Storage
`16.3 Handling
`17 PATIENT COUNSELING INFORMATION
`*Sections or subsections omitted from the full prescribing information are not list.
`
`11
`12
`
`14
`16
`
`Regeneron Exhibit 1192.001
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`IPR2021-00816
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`BLA 761197
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`FULL PRESCRIBING INFORMATION
`
`WARNING: ENDOPHTHALMITIS
`The SUSVIMO implant has been associated with a 3-fold higher rate of endophthalmitis
`than monthly intravitreal injections of ranibizumab. Many of these events were
`associated with conjunctival retractions or erosions. Appropriate conjunctiva
`management and early detection with surgical repair of conjunctival retractions or
`erosions may reduce the risk of endophthalmitis. In clinical trials, 2.0% of patients
`
`receiving a ranibizumab implant experienced at least one episode of endophthalmitis [see
`
`Contraindications (4.1), Warnings and Precautions (5.1)].
`
`INDICATIONS AND USAGE
`1
`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
`
`2.1 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 x 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 x 1½ inch), and a 1 mL Luer lock
`syringe are needed but not included.
`
`Neovascular (Wet) Age-Related Macular Degeneration (AMD)
`2.2
`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).
`
`2.3
`
`Supplemental Treatment with Intravitreal Ranibizumab Injection
`
`Reference ID: 4876896
`
`Regeneron Exhibit 1192.002
`Regeneron v. Novartis
`IPR2021-00816
`
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`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)].
`
`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 x 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.
`
`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
`
`Figure 1
`
`Reference ID: 4876896
`
`Regeneron Exhibit 1192.003
`Regeneron v. Novartis
`IPR2021-00816
`
`

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`filter needle into the syringe.
` Remove and properly dispose of the filter
`
`needle after withdrawal of the vial
`contents.
`Step 3: 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 2). 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.
`
`Step 4: Remove Air from Syringe
` 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 3).
` 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 4).
`
`Note: It is important to preserve as much drug
`as possible in order to completely fill
`the implant.
`
`Figure 2
`
`Figure 3
`
`Reference ID: 4876896
`
`Regeneron Exhibit 1192.004
`Regeneron v. Novartis
`IPR2021-00816
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`Step 5: Inspect the Syringe for Air Bubbles
` Inspect the syringe and the needle hub to
`ensure that no air bubbles are present (see
`Figure 5).
` If air bubbles are present, continue to
`
`remove air from the syringe and reinspect.
`
`
`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 6: 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 6).
` Push the syringe forward until it stops,
`taking care to avoid touching the plunger
`
`rod (see Figure 7)
`
`Figure 4
`
`Figure 5
`
`Figure 6: Align and lower the syringe into
`the carrier
`
`Reference ID: 4876896
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`Regeneron Exhibit 1192.005
`Regeneron v. Novartis
`IPR2021-00816
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`  With the syringe loaded, (see Figure 8) the
`
`initial fill needle should now be penetrating
`the implant septum.
`
`
`
` Figure 7: Push the syringe into the carrier
`
`
`
`
`
`Figure 8: Syringe with initial fill needle
`inserted through the implant septum
`
`Reference ID: 4876896
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`Regeneron Exhibit 1192.006
`Regeneron v. Novartis
`IPR2021-00816
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`Step 7: 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 9).
`
` The ocular implant should be filled over
`approximately 5 to 10 seconds, to help
`avoid air entrapment in the implant
`reservoir.
`
`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 10).
`
`
`
` Figure 9: Administer ranibizumab into the
`implant
`
`Figure 10: Dome of drug solution forms at
`tip of implant as viewed under magnification
`
`Reference ID: 4876896
`
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`Regeneron v. Novartis
`IPR2021-00816
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`Step 8: 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 11).
`
`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 9: 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 12). 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 11: Proper appearance of implant after
`initial filling with ranibizumab
`
`Figure 12: Remove the syringe and guide
`
`sleeve from the insertion tool carrier
`
`Reference ID: 4876896
`
`Regeneron Exhibit 1192.008
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`IPR2021-00816
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`Step 10: 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 13).
` Push the handle forward as far as it will
`go into the gripper tips (see Figure 14).
`
`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.
`
`Figure 13: Insert the handle into the insertion
`tool carrier
`
`Figure 14: Fully inserted handle
`
`2.5 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 6x6 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 (2.4)]. 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,
`
`Reference ID: 4876896
`
`Regeneron Exhibit 1192.009
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`IPR2021-00816
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`ensuring complete coverage of the implant flange. 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.
`
`2.6 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 6x6 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 Use
`for the implant removal procedure included in the explant tool carton for further details.
`
`
`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.
`
`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 x 1½ inch) (not included)
`
`Reference ID: 4876896
`
`Regeneron Exhibit 1192.010
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`IPR2021-00816
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`

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`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 15).
`
`
`
`
`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
`
`Figure 15
`
`Reference ID: 4876896
`
`Regeneron Exhibit 1192.011
`Regeneron v. Novartis
`IPR2021-00816
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`
`Do not use if particulate, cloudiness, or
`discoloration are visible.
`
`Step 4: Patient Preparation
` 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.
`
` Dilate the pupil of the eye.
` 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
`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 16).
` 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.
`
`Figure 16
`
`Reference ID: 4876896
`
`Regeneron Exhibit 1192.012
`Regeneron v. Novartis
`IPR2021-00816
`
`

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`
` Remove and properly dispose of the filter
`needle after withdrawal of the vial
`contents.
`
`Step 6: 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 17). 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.
`
`
`Step 7: Remove Air from Syringe and
`Adjust Drug Dose
` 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 18).
`
`
`
`Figure 17
`
`Figure 18
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`Reference ID: 4876896
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` 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 19).
`
`Step 8: Inspect the Syringe for Air Bubbles
`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 20).
`
`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.
`
`Figure 19
`
`Figure 20
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`Reference ID: 4876896
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`Step 9: Stabilize the globe and orient the
`refill needle
`
`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 21).
`— 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 22).
`
`Step 10: Insert the Refill Needle
`
` 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
`23).
`
`
`
` Figure 21
`
`
`Figure 22
`
`Figure 23
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`Reference ID: 4876896
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`— If excessive resistance, withdraw the
`refill needle. Orient and insert again.
`— Once the needle is aligned with the
`septum, if resistance is encountered a
`
`slight rotation of the refill needle
`around its axis may help to facilitate
`the passage of the needle. 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
`
`24) to provide a tactile cue that optimal
`contact has been made.
`
`Step 11: 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 25).
`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 24
`
`Figure 25
`
`Reference ID: 4876896
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`Step 12: Withdraw the Syringe
` Withdraw the syringe perpendicular to the
`globe to avoid damaging the septum (see
`Figure 26).
` A cotton-tipped applicator may be used to
`provide counter traction to the conjunctiva
`during needle withdrawal.
`
`Figure 26
`
`Step 13: 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 14: Perform Indirect Ophthalmoscopy
` Perform indirect ophthalmoscopy to
`ensure continued proper position of the
`
`implant in the vitreous cavity and to
`examine for complications.
`
`Delayed or Missed Doses
`2.8
`If a planned dose (refill-exchange) of SUSVIMO (ranibizumab injection) is missed, it should be
`administered as soon as possible and the subsequent refill-exchange procedures should be
`performed 24 weeks (approximately 6 months) thereafter.
`
`Dosage (Refill-Exchange) Modifications for Adverse Reactions
`2.9
`Table 1 describes dosage modifications for specific adverse Reactions [see Warnings and
`Precautions (5)]. No dosage reductions for SUSVIMO are recommended.
`
`Table 1: Dosage (Refill-Exchange) Modifications for Adverse Reactions
`Adverse Reactions
`Dosage Modification
`Intraocular inflammation ≥ 1 + cells or flare Withhold dose (refill-exchange)
`Withhold dose (refill-exchange)
`Sight threatening events (e.g.,
`rhegmatogenous retinal detachment, vitreous
`hemorrhage, unexplained vision loss, etc.)
`Local infections of either eye
`
` Infectious endophthalmitis
`Severe systemic infection
`
`Withhold dose (refill-exchange)
`Withhold dose (refill-exchange)
`Withhold dose (refill-exchange)
`
`Reference ID: 4876896
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`Observed damage to the implant
`
` Withhold dose (refill-exchange) and consider
`
`SUSVIMO implant removal [see Dosage and
`Administration (2.6)].
`
`DOSAGE FORMS AND STRENGTHS
`3
`Injection: 100 mg/mL, clear to slightly opalescent, colorless to pale brown solution in a
`single-dose vial
`
`4
`CONTRAINDICATIONS
`
`4.1 Ocular or Periocular Infections
`SUSVIMO (ranibizumab injection) is contraindicated in patients with ocular or periocular
`infections.
`
`
`4.2
`Active Intraocular Inflammation
`SUSVIMO (ranibizumab injection) is contraindicated in patients with active intraocular
`inflammation.
`
`4.3 Hypersensitivity
`SUSVIMO (ranibizumab injection) is contraindicated in patients with known hypersensitivity to
`ranibizumab products or any of the excipients in SUSVIMO (ranibizumab injection).
`
`WARNINGS AND PRECAUTIONS
`5
`The SUSVIMO implant and/or implant-related procedures have been associated with
`endophthalmitis, rhegmatogenous retinal detachment, implant dislocation, 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)].
`
`Endophthalmitis
`5.1
`In the active comparator period of controlled clinical trials, the ranibizumab implant has been
`associated with a 3-fold higher rate of endophthalmitis than monthly intravitreal injections of
`ranibizumab (1.7% in the SUSVIMO arm vs 0.5% in the intravitreal arm). When including
`extension phases of clinical trials, 2.0% (11/555) of patients receiving the ranibizumab implant
`experienced an episode of endophthalmitis. Reports occurred between days 5 and 853, with a
`median of 173 days. Many, but not all, of the cases of endophthalmitis reported a preceding or
`concurrent conjunctival retraction or erosion event.
`
`Endophthalmitis should be treated promptly in an effort to reduce the risk of vision loss and
`maximize recovery. The SUSVIMO (ranibizumab injection) dose (refill-exchange) should be
`delayed until resolution of endophthalmitis [see Dosage and Administration (2.9) and Adverse
`Reactions (6.1)].
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`Reference ID: 4876896
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`Patients should not have an active or suspected ocular or periocular infection or severe systemic
`infection at the time of any SUSVIMO implant or refill procedure. Appropriate intraoperative
`handling followed by secure closure of the conjunctiva and Tenon’s capsule, and early detection
`and surgical repair of conjunc