Aucatzyl

Irradiation could lead to inactivation of the product. Precautions to be taken before handling or administering the medicinal product Aucatzyl must be transported within the treatment centre in closed, break-proof, leak-proof containers. This medicinal product contains genetically modified human blood cells.‍‍‍‍‍‍​​​‍​​​​​​ Healthcare professionals handling Aucatzyl must take appropriate precautions (wearing gloves, protective clothing and eye protection) to avoid potential transmission of infectious diseases. Preparation prior to administration Confirm availability of Aucatzyl before starting the lymphodepleting chemotherapy regimen. Patients should be clinically re-assessed prior to administration of lymphodepleting chemotherapy and Aucatzyl to ensure that there are no reasons to delay therapy (see section 4.4, Reasons to delay treatment). Receipt and storage of Aucatzyl • Aucatzyl is supplied directly to the cellular therapy laboratory associated with the infusion centre in the vapour phase of a liquid nitrogen shipper (≤ -150ºC). • Confirm the patient's identity on the infusion bags with the patient identifiers on the Release for Infusion Certificate, see Figure 2. Figure 2: Patient Specific Identifiers • Keep the infusion bag(s) in the metal cassette(s) and transfer Aucatzyl to the onsite controlled-access vapour phase of liquid nitrogen for storage ≤ -150 ºC (until ready for thaw and administration). • Time out of the vapour phase liquid nitrogen environment should be kept to an absolute minimum to avoid premature product thaw (recommend not to exceed 90 seconds). Planning prior to Aucatzyl preparation The patient batch-specific Release for Infusion Certificate and Dose Schedule Planner will be provided in the shipper and via Autolus Scheduling Portal. Confirm the patient identifiers on Release for Infusion Certificate and infusion bags match, Figure 2. 1. Ensure the patient's bone marrow assessment results are available (see section 4.2, Bone marrow assessment). NOTE: The patient's bone marrow lymphoblast assessment results will be used to select the appropriate dosing regimen: High Tumour Burden Dosage Regimen if the lymphoblast percentage is > 20% or inconclusive or Low Tumour Burden Dosage Regimen if the lymphoblast percentage is ≤ 20%. 2. The Aucatzyl Dose Schedule Planner, provided with the Release for Infusion Certificate, assists the determination of the appropriate dose regimen to be administered on Day 1 (3 days ± 1 day after the completion of lymphodepleting chemotherapy) and Day 10 (± 2 days). Record the following information on the Dose Schedule Planner: a. The lymphoblast percentage from the patient's bone marrow assessment b. The Aucatzyl bag serial number(s); number of bag type required for each dose; and the specified volume to administer via syringe (for the 10 × 10 6 Dose) transcribed from the Release for Infusion Certificate. 3. The completion of the Aucatzyl Dose Schedule Planner will guide the treating physician on the number of bags and the respective dose required, and the preparation of Aucatzyl for the Day 1 and Day 10 (± 2 days) dose. Transfer and Thawing • Using the completed Dose Schedule Planner for guidance, transfer only the cassette(s) / infusion bag(s) required for the given dosing day from the onsite vapour-phase liquid nitrogen storage to an appropriate transfer vessel (i.e., a vapour-phase liquid nitrogen shipper, maintaining temperature ≤ -150ºC) for transport to the bag thaw location. • Transfer the required cassette(s) one by one, confirming the Aucatzyl bag serial numbers and patient identifiers on each infusion bag label, see Figure 2. • Time out of the vapour phase liquid nitrogen environment should be kept to an absolute minimum to avoid premature product thaw (recommend not to exceed 90 seconds). • If more than one infusion bag has been required on a given dosing day, thaw each infusion bag one at a time; do not remove subsequent bags from the vapour-phase liquid nitrogen storage (≤ -150ºC) until infusion of the previous bag is complete. • Aucatzyl must be continuously monitored during the thawing process. • Leave the Aucatzyl infusion bag in its overwrap, thaw at 37ºC using a water bath or thawing device until there are no visible frozen clumps left in the infusion bag. Each bag should be gently massaged until the cells have just thawed. Thawing of each infusion bag takes between 2 to 8 minutes. Remove from the water bath or thaw device immediately after thawing is complete. Carefully remove the infusion bag from the overwrap taking care to avoid damage to the bag and ports. • Gently mix the contents of the bag to disperse clumps of cellular material and administer immediately to the patient. • Do not re-freeze or refrigerate thawed product. Infusion Instructions Aucatzyl is for autologous and intravenous use only (see section 4.4). The patient's identity must match the patient identifiers on the Aucatzyl Release for Infusion Certificate and infusion bag. Contact Autolus at 00800 0825 0829 if there are any discrepancies between the labels and the patient identifiers. Dose administration for 10 × 10 6 CD19 CAR-positive viable T cells (syringe-based infusion) Withdrawal of the 10 × 10 6 dose into the syringe should be carried out as follows: • Prepare and administer Aucatzyl using aseptic technique. • Gently mix the contents of the bag to disperse clumps of cellular material. • The volume to be administered for the 10 × 10 6 dose is specified on the Release for Infusion Certificate. • Use the smallest Luer-lock tip syringe necessary (1, 3, 5, or 10 mL) with a Luer-lock bag spike to draw up the volume specified on the Release for Infusion Certificate. o Do not use a leukodepleting filter. o Do not use the syringe to mix the cells, see Figure 3. Figure 3: Syringe Infusion Guidance for 10 × 10 6 Dose • Prime the tubing with normal saline prior to infusion. • Once Aucatzyl has been drawn into the syringe, verify the volume and administer as an intravenous infusion as soon as possible (as a slow push approximately 0.5 mL/minute) through a central venous line (or large peripheral venous access line appropriate for blood products). • Complete infusion at room temperature within 60 minutes post-thaw and flush the tubing line with 60 mL of normal saline. • Dispose of any unused portion of Aucatzyl (according to local biosafety guidelines). Dose administration for 100 × 10 6 and/or 300 × 10 6 CD19 CAR-positive viable T cells • Refer to the Release for Infusion Certificate for the following details: o The volume and total CD19 CAR-positive viable T cell number contained in each infusion bag. o The dose to be administered on the given dosing day and the number of bags required to deliver the specified CD19 CAR-positive viable T cell dose. o If more than one bag is needed, thaw subsequent bag after the previous bag is fully administered. 1. Prime the tubing with normal saline prior to infusion. 2. Administer Aucatzyl via a gravity or peristaltic pump assisted intravenous infusion through a central venous line (or large peripheral venous access line appropriate for blood products). • Do not use a leukodepleting filter. • Aseptic techniques must be applied when performing a venepuncture (if applicable), spiking the ports, and through cell administration process. • Gently mix the contents of the bag during Aucatzyl infusion to disperse cell clumps. 3. Infuse the entire content of the Aucatzyl infusion bag at room temperature within 60 minutes post-thaw. • After the entire contents of the infusion bag is infused, rinse the bag with 30 mL of normal saline, then flush the tubing line with 60 mL of normal saline. • Repeat steps 1-3 for any additional infusion bags required on the given dosing day. Do not initiate thaw of the next bag until infusion of the previous bag is complete. Measures to take in case of accidental exposure In case of accidental exposure, local guidelines on handling of human-derived material must be followed. Work surfaces and materials which have potentially been in contact with Aucatzyl must be decontaminated with appropriate disinfectant. Precautions to be taken for the disposal of the medicinal product Unused medicinal product and all material that has been in contact with Aucatzyl (solid and liquid waste) must be handled and disposed of as potentially infectious waste in accordance with local guidelines on handling of human-derived material.