Recommended Dosage

In adults, the recommended amount of radioactivity to be administered for PET is 111 MBq to 259 MBq (3 mCi to 7 mCi) administered as an intravenous bolus injection.

Administration

• Use aseptic technique and radiation shielding when withdrawing and administering Gallium Ga 68 Gozetotide Injection.
• Calculate the necessary volume to administer based on calibration time and required dose.
• Inspect Gallium Ga 68 Gozetotide Injection visually for particulate matter and discoloration before administration. Only use solutions that are clear, colorless to slightly yellow, and without visible particles.
• Assay the final dose in a dose calibrator immediately before administration to the patient.
• After injection of Gallium Ga 68 Gozetotide Injection, administer an intravenous flush of sterile 0.9% Sodium Chloride Injection to ensure full delivery of the dose.
• Dispose of any unused drug in a safe manner in compliance with applicable regulations.
• Unless contraindicated, a diuretic expected to act within the uptake time period may be administered at the time of radiotracer injection to potentially decrease artifact from radiotracer accumulation in the urinary bladder and ureters.

Ga 68 Sources and GOZELLIX Carton Configurations

GOZELLIX is supplied as a kit in two different carton configurations, A or B, for preparation of Gallium Ga 68 Gozetotide Injection with eluate from different Ga 68 sources. See Table 1for GOZELLIX carton configurations to be used with different Ga 68 sources.

The Ge 68/Ga 68 generators and cyclotron are not supplied with GOZELLIX. Follow the instructions for use provided by the Ge 68/Ga 68 generator or cyclotron manufacturer.

Components of GOZELLIX consist of Vial 1 (Gozetotide), Vial 2A or Vial 2B (Acetate Buffer), and an Ampule (Ascorbic Acid Stabilizer) [see How Supplied/Storage and Handling (16)] .

General Instructions

1. Follow aseptic techniques in all drug preparation and handling.
2. Use suitable shielding to reduce radiation exposure.
3. Wear waterproof gloves.
4. Place a "radioactive" label on Vial 1 (Gozetotide) with product name, lot number and date.
5. Remove the vial cap from Vial 1 (Gozetotide) and Vial 2A or Vial 2B (Acetate Buffer).
6. Swab the top of each vial and the outside of the ampule with alcohol to disinfect the surface and allow the top of each vial to dry.
7. Use the shortest possible needle for the transfer of the Gallium Ga 68 Chloride solution to minimize any potential metallic contamination. The needle should be clean and dilute acid resistant.
8. Use only plastic syringes for preparation and administration. Do notuse syringes with rubber plungers.
9. Prior to use of any vial, confirm the correct vial by a visual check of the vial label.
10. Prepare the acetate buffer by adding 0.10 mL ascorbic acid stabilizer according to the instruction below before proceeding with the specific procedure depending on Ga 68 source.
11. Follow the specific preparation procedure dependent on Ga 68 source [see Dosage and Administration (2.5, 2.6, 2.7, 2.8)] .

Procedure for Addition of Ascorbic Acid Stabilizer to Acetate Buffer

1. Safely open the ascorbic acid stabilizer ampule.
2. Using an appropriately sized syringe (e.g., 0.5 mL syringe) fitted with a 5 micron 18 G × 1 1/2 inch sterile filter needle or equivalent, withdraw the solution of ascorbic acid, through the filter needle.
   NOTE: The syringe must contain at least 0.10 mL of ascorbic acid stabilizer solution that can then be dispensed. The operator must account for the dead volume of the syringe and filter needle.
3. Remove the filter needle from the syringe and fit a sterile needle to the syringe containing the ascorbic acid.
4. Dispense 0.10 mL of the ascorbic acid stabilizer solution from the syringe into the acetate buffer vial (Vial 2A or Vial 2B).
5. After removal of the syringe from the vial, mix the contents by inverting the vial at least three times.

Collection of Gallium Ga 68 Chloride Solution

After purification by the FASTlab, the Gallium Ga 68 Chloride solution is passed through a sterile filter and into the cassette product vial automatically by the FASTlab.

When Ga 68 is cyclotron-produced, test for Ga 66 and Ga 67 (with specification of ≤2% combined total) when a new lot of Zn 68 is introduced for manufacturing.

Radiolabeling Procedure

1. Use GOZELLIX "Configuration A" with cyclotron-produced Ga 68 via GE FASTlab Solid or Liquid Target System.
2. A schematic diagram for the preparation is provided in Figure 1.
3. Prepare the acetate buffer (Vial 2A) with ascorbic acid stabilizer as outlined in the procedure above [see Dosage and Administration (2.4)] .
4. Pierce Vial 1 (Gozetotide) with a sterile needle connected to a 0.2 micron sterile vented filter to maintain atmospheric pressure within the vial during the reconstitution process.
5. Insert a sterile syringe with a needle into Vial 2A containing the acetate and ascorbic acid buffer solution and draw up 2.6 mL of the solution.
6. Aseptically transfer the acetate and ascorbic acid buffer solution in the syringe into Vial 1 (Gozetotide).
7. Gently swirl Vial 1 to ensure the product is thoroughly dissolved in the buffer.
8. Aseptically transfer the 5 mL of Gallium Ga 68 Chloride solution made using the GE FASTlab Solid or Liquid Target System into Vial 1 (Gozetotide).
9. Remove the sterile vent filter.
10. Gently swirl Vial 1 to ensure the product is thoroughly mixed.
11. Wait for 5 minutes for radiolabeling to take place at room temperature (25°C (77°F); excursions permitted to 15°C to 30°C (59°F to 86°F)).
12. Assay the whole vial containing the Gallium Ga 68 Gozetotide Injection for total radioactivity using a dose calibrator, calculate the radioactivity concentration, and record the result.
13. Dilute the Gallium Ga 68 Gozetotide Injection with 2.4 mL of 0.9% Sodium Chloride Injection to a final volume of 10 mL.
14. Perform the quality control of Gallium Ga 68 Gozetotide Injection according to the recommended methods [see Dosage and Administration (2.9)] .
15. Prior to use, visually inspect the solution behind a shielded screen for radioprotection purposes. Only use solutions that are clear without visible particles.
16. Keep the vial containing the Gallium Ga 68 Gozetotide Injection upright in a radioprotective shield container at room temperature until use.
17. The final volume of the Gallium Ga 68 Gozetotide Injection is 10 mL after dilution with 0.9% Sodium Chloride Injection.
18. Use within 4 hours if preparation contains less than 2,590 MBq (70 mCi) or within 6 hours if preparation contains 2,590 MBq to 18,500 MBq (70 mCi to 500 mCi) .

Figure 1: Drug Preparation with Cyclotron-Produced Ga 68 via GE FASTlab Solid or Liquid Target System

Collection of Gallium Ga 68 Chloride Solution

After purification by the ARTMS QIS, the Gallium Ga 68 Chloride solution is passed through a sterile filter and into the cassette product vial automatically by the ARTMS QIS.

When Ga 68 is cyclotron-produced, test for Ga 66 and Ga 67 (with specification of ≤2% combined total) when a new lot of Zn 68 is introduced for manufacturing.

Radiolabeling Procedure

1. Use GOZELLIX "Configuration A" with cyclotron-produced Ga 68 via ARTMS QIS Solid Target System.
2. A schematic diagram for the preparation is provided in Figure 2.
3. Prepare the acetate buffer (Vial 2A) with ascorbic acid stabilizer as outlined in the procedure above [see Dosage and Administration (2.4)] .
4. Pierce Vial 1 (Gozetotide) with a sterile needle connected to a 0.2 micron sterile vented filter to maintain atmospheric pressure within the vial during the reconstitution process.
5. Insert a sterile syringe with a needle into Vial 2A containing the acetate and ascorbic acid buffer solution and draw up 2.6 mL of the solution.
6. Aseptically transfer the acetate and ascorbic acid buffer solution in the syringe into Vial 1 (Gozetotide).
7. Gently swirl Vial 1 to ensure the product is thoroughly dissolved in the buffer.
8. Aseptically transfer the 5 mL of Gallium Ga 68 Chloride solution made using the ARTMS QIS Solid Target System into Vial 1 (Gozetotide).
9. Remove the sterile vent filter.
10. Gently swirl Vial 1 to ensure the product is thoroughly mixed.
11. Wait for 5 minutes for radiolabeling to take place at room temperature (25°C (77°F)); excursions permitted to 15°C to 30°C (59°F to 86°F)).
12. Assay the whole vial containing the Gallium Ga 68 Gozetotide Injection for total radioactivity using a dose calibrator, calculate the radioactivity concentration, and record the result.
13. Dilute the Gallium Ga 68 Gozetotide Injection with 2.4 mL of 0.9% Sodium Chloride Injection to a final volume of 10 mL.
14. Perform the quality control of Gallium Ga 68 Gozetotide Injection according to the recommended methods [see Dosage and Administration (2.9)] .
15. Prior to use, visually inspect the solution behind a shielded screen for radioprotection purposes. Only use solutions that are clear without visible particles.
16. Keep the vial containing the Gallium Ga 68 Gozetotide Injection upright in a radioprotective shield container at room temperature until use.
17. The final volume of the Gallium Ga 68 Gozetotide Injection is 10 mL after dilution with 0.9% Sodium Chloride Injection.
18. Use within 4 hours if preparation contains less than 2,590 MBq (70 mCi) or within 6 hours if preparation contains 2,590 MBq to 18,500 MBq (70 mCi to 500 mCi).

Figure 2: Drug Preparation with Cyclotron-Produced Ga 68 via ARTMS QIS Solid Target System

Radiolabeling Procedure

1. Use GOZELLIX "Configuration A" with an EZAG GalliaPharm generator.
2. A schematic diagram for the preparation is provided in Figure 3.
3. Prepare the acetate buffer vial (Vial 2A) with ascorbic acid stabilizer as outlined in the procedure above [see Dosage and Administration (2.4)] .
4. Pierce Vial 1 (Gozetotide) with a sterile needle connected to a 0.2 micron sterile vented filter to maintain atmospheric pressure within the vial during the reconstitution process.
5. Insert a sterile syringe with a needle into Vial 2A containing the acetate and ascorbic acid buffer solution and draw up 2.6 mL of the solution.
6. Aseptically transfer the acetate and ascorbic acid buffer solution in the syringe into Vial 1 (Gozetotide).
7. Gently swirl Vial 1 to ensure the product is thoroughly dissolved in the buffer.
8. Prepare a syringe containing 5 mL of sterile ultrapure 0.1 M HCl provided with the GalliaPharm generator for elution.
9. Connect the male luer of the outlet line of the GalliaPharm generator to a sterile needle.
10. Connect Vial 1 containing the dissolved gozetotide solution directly to the outlet line of the GalliaPharm generator by pushing the needle through the rubber septum and place the vial in a radiation shielded container.
11. Ensure the vent needle and needle to the generator outlet are pulled up as far as possible to not contact the solution in the vial.
12. Elute the generator directly with the 5 mL 0.1 M HCl from step 8 into Vial 1 according to the instructions for use of the GalliaPharm generator that are supplied by EZAG.
13. At the end of the elution, disconnect the generator from Vial 1 by removing the needle from the rubber septum and remove the sterile vent filter.
14. Gently swirl the vial to ensure the product is thoroughly mixed.
15. Wait for 5 minutes for radiolabeling to take place at room temperature (25°C (77°F); excursions permitted to 15°C to 30°C (59°F to 86°F)).
16. Assay the whole vial containing the Gallium Ga 68 Gozetotide Injection for total radioactivity using a dose calibrator, calculate the radioactivity concentration, and record the result.
17. Dilute the Gallium Ga 68 Gozetotide Injection with 2.4 mL of 0.9% Sodium Chloride Injection to a final volume of 10 mL.
18. Perform the quality control of Gallium Ga 68 Gozetotide Injection according to the recommended methods [see Dosage and Administration (2.9)] .
19. Prior to use, visually inspect the solution behind a shielded screen for radioprotection purposes. Only use solutions that are clear without visible particles.
20. Keep the vial containing the Gallium Ga 68 Gozetotide Injection upright in a radioprotective shield container at room temperature until use.
21. The final volume of the Gallium Ga 68 Gozetotide Injection is 10 mL after dilution with 0.9% Sodium Chloride Injection.
22. Use within 4 hours if preparation contains less than 2,590 MBq (70 mCi) or within 6 hours if preparation contains 2,590 MBq to 18,500 MBq (70 mCi to 500 mCi).

Figure 3: Preparation with EZAG GalliaPharm Generator

Radiolabeling Procedure

1. Use GOZELLIX "Configuration B" with an IRE EliT Galli Eo generator.
2. A schematic diagram for the preparation is provided in Figure 4.
3. Prepare the acetate buffer vial (Vial 2B) with ascorbic acid stabilizer as outlined in the procedure above [see Dosage and Administration (2.4)] .
4. Pierce Vial 1 (Gozetotide) with a sterile needle connected to a 0.2 micron sterile vented filter to maintain atmospheric pressure within the vial during the reconstitution process.
5. Insert a sterile syringe with a needle into Vial 2B containing the acetate and ascorbic acid buffer solution and draw up 6.5 mL of the solution.
6. Aseptically transfer the acetate and ascorbic acid buffer solution in the syringe into Vial 1 (Gozetotide).
7. Gently swirl Vial 1 to ensure the product is thoroughly dissolved in the buffer.
8. Remove the 0.2 micron sterile vented filter from Vial 1.
9. Connect the male luer of the outlet line of the Galli Eo generator to a sterile needle.
10. Connect Vial 1 containing the dissolved gozetotide solution directly to the outlet line of the Galli Eo generator by pushing the needle through the vial's septum.
11. Ensure the needle to the generator outlet is pulled up as far as possible to not contact the solution in the vial.
12. Elute 1.1 mL from the generator directly into Vial 1 (Gozetotide) according to the instructions for use of the Galli Eo generator that are supplied by IRE that describe elution into a non-evacuated vial.
13. At the end of the elution, disconnect the generator from Vial 1 by removing the needle from the rubber septum.
14. Gently swirl Vial 1 to ensure the product is thoroughly mixed.
15. Wait for 5 minutes for radiolabeling to take place at room temperature (25°C (77°F); excursions permitted to 15°C to 30°C (59°F to 86°F)).
16. Assay the whole vial containing the Gallium 68 Gozetotide Injection for total radioactivity using a dose calibrator, calculate the radioactivity concentration, and record the result.
17. Dilute the Gallium Ga 68 Gozetotide Injection with 2.4 mL of 0.9% Sodium Chloride Injection to a final volume of 10 mL.
18. Perform the quality control of Gallium Ga 68 Gozetotide Injection according to the recommended methods [see Dosage and Administration (2.9)] .
19. Prior to use, visually inspect the solution behind a shielded screen for radioprotection purposes. Only use solutions that are clear without visible particles.
20. Keep the vial containing the Gallium Ga 68 Gozetotide Injection upright in a radioprotective shield container at room temperature until use.
21. The final volume of the Gallium Ga 68 Gozetotide Injection is 10 mL after dilution with 0.9% Sodium Chloride Injection.
22. Use within 4 hours if preparation contains less than 2,590 MBq (70 mCi) or within 6 hours if preparation contains 2,590 MBq to 18,500 MBq (70 mCi to 500 mCi).

Figure 4: Preparation with IRE ELiT Galli Eo Generator

Procedure for instant Thin Layer Chromatography (iTLC)

1. Pour ammonium acetate 1 M/methanol (1/1 v/v) solution to a depth of 3 mm to 4 mm in the developing chamber, cover the chamber and allow it to equilibrate.
2. Prepare an iTLC strip that is 12 cm in length approximately 2.5 cm in width.
3. Using a pencil and ruler, carefully draw a solid line at least 1 cm from the bottom of the iTLC strip.
4. Using a pencil and ruler, carefully draw a solid line 10 cm above the pencil line drawn in Step 3.
5. Using a pencil and ruler, draw a dotted line 2 cm above the solid line at the bottom of the iTLC strip.
6. Using a pencil and ruler, draw a second dotted line 6 cm above the solid line at the bottom of the iTLC strip. Mark the section below this line with an "X". See Figure 5for an example of how to mark the iTLC strip.
7. Apply a drop of gallium Ga 68 gozetotide solution into the center of the solid line at 1 cm from the bottom of the TLC plate.
8. Place the iTLC strip into the development chamber, with the bottom of the iTLC strip containing drop of gallium Ga 68 gozetotide into the solution at the bottom of the developing chamber. Ensure that the bottom of the iTLC strip sits in the liquid in the chamber, but that the liquid does not touch the drop of gallium Ga 68 gozetotide.
9. Allow the iTLC strip to develop in the covered chamber over a distance of 10 cm from the point of application (until the solvent reaches the solid line near the top of the iTLC strip).
10. Remove the iTLC strip. Allow the plate to dry before proceeding with analysis using one of the methods described below.

Perform one of the following:

Radiochemical Purity Analysis Using Cutting Technique

1. Cut the iTLC strip into 3 parts by cutting horizontally at the dotted line 2 cm above the solid line at the bottom of the iTLC strip and the dotted line 6 cm above the solid line at the bottom of the iTLC strip. See Figure 5for where to cut the iTLC strip.
2. This cutting will result in the following 3 portions:
   1. A 3 cm portion containing the Origin and free/colloidal Ga 68 species (Bottom Portion)
   2. A 4 cm portion marked with an "X" containing no sample (this portion is NOT measured)
   3. A 5 cm portion containing the solvent front and gallium Ga 68 gozetotide (Top Portion)
3. Using a dose calibrator or gamma spectrometer, measure and record the radioactivity in the 3 cm portion of the cut TLC plate that contains the Origin and free/colloidal Ga 68 species (Bottom Portion).
4. Using a dose calibrator or gamma spectrometer, measure and record the radioactivity in the 5 cm portion containing the solvent front and gallium Ga 68 gozetotide (Top Portion).
5. Calculate the quantity (in percent) of gallium Ga 68 gozetotide in the solution using the formula:

Radiochemical Purity (%)
	=	Counts Top Portion	× 100
		Counts from Top Portion + Counts from Bottom Portion

Figure 5: iTLC Strip Preparation and Cutting Points for the Cutting Technique

Risk Summary

GOZELLIX is not indicated for use in females. There are no available data with gallium Ga 68 gozetotide injection use in pregnant women to evaluate for a drug-associated risk of major birth defects, miscarriage, or adverse maternal or fetal outcomes. All radiopharmaceuticals, including GOZELLIX, have the potential to cause fetal harm depending on the fetal stage of development and the magnitude of the radiation dose. Animal reproduction studies have not been conducted with gallium Ga 68 gozetotide.

Risk Summary

GOZELLIX is not indicated for use in females. There are no data on the presence of gallium Ga 68 gozetotide in human milk, the effect on the breastfed infant, or the effect on milk production.

Kit Characteristics

GOZELLIX is supplied as a kit which contains the non-radioactive ingredients needed to produce Gallium Ga 68 Gozetotide Injection. There are two configurations, A or B, available to allow preparation of Gallium Ga 68 Gozetotide Injection using Ga 68 from different generator or cyclotron sources. Each configuration consists of gozetotide (Vial 1), acetate buffer (Vial 2A or Vial 2B), and ascorbic acid stabilizer (Ampule).

• Vial 1 (Gozetotide): Each vial contains 25 mcg gozetotide and 10 mcg D-mannose.
• Vial 2A (Acetate Buffer): Each vial contains 150 mg anhydrous sodium acetate in 2.5 mL of 0.292 M hydrochloric acid.
• Vial 2B (Acetate Buffer): Each vial contains 150 mg anhydrous sodium acetate in 6.4 mL of 0.175 M hydrochloric acid.
• Ampule (Ascorbic Acid Stabilizer): Each ampule contains 500 mg of ascorbic acid (USP injection grade), 3 mg sodium metabisulfite, sodium hydroxide for pH adjustment, and water for injection in a volume of 2 mL.

The prepared Gallium Ga 68 Gozetotide Injection is a sterile, pyrogen free, clear, colorless to slightly yellow, buffered solution containing up to 18,500 MBq (500 mCi) of gallium Ga 68 gozetotide in 10 mL with a pH between 4.0 to 5.0.

Distribution

Intravenously injected gallium Ga 68 gozetotide is cleared from the blood and is accumulated preferentially in the liver (15%), kidneys (7%), spleen (2%), and salivary glands (0.5%). Gallium Ga 68 gozetotide uptake is also seen in the adrenals and prostate. There is no uptake in the cerebral cortex or in the heart, and usually lung uptake is low.

Elimination

A total of 14% of the injected dose is excreted in urine in the first 2 hours post-injection.