Mobilization and Apheresis

Patients are required to undergo HSC mobilization followed by apheresis to obtain CD34+ cells for product manufacturing. Weigh the patient prior to the first apheresis collection. Collect a minimum target number of CD34+ cells of 12 × 106 CD34+ cells/kg.

A back-up collection of CD34+ cells of ≥ 1.5 × 106 CD34+ cells/kg (if collected by apheresis) or ≥ 1.0 × 108 TNC/kg (Total Nucleated Cells, if collected by bone marrow harvest) is required. Collect and cryopreserve these cells prior to initiating conditioning and infusion with SKYSONA. The back-up collection may be needed for rescue treatment if there is: 1) compromise of SKYSONA after initiation of conditioning and before SKYSONA infusion, 2) primary engraftment failure, or 3) loss of engraftment after infusion with SKYSONA.

Myeloablative and Lymphodepleting Conditioning

Full myeloablative and lymphodepleting conditioning must be administered before infusion of SKYSONA. Consult prescribing information for the conditioning agents prior to treatment.

Do not begin conditioning until SKYSONA has been received and stored at the treatment center and the availability of the back-up collection of CD34+ cells is confirmed. After completion of conditioning, allow a minimum of 48 hours of washout before SKYSONA infusion.

Receipt and Storage of SKYSONA

• Ensure the availability of vapor phase of liquid nitrogen storage at less than or equal to -140°C (-220°F) at the treatment center.
• SKYSONA is shipped to the treatment center in the vapor phase of liquid nitrogen shipper.
• Confirm Patient Identifiers on the product labels and Lot Information Sheet within the shipper.
• If there are any concerns about the product or packaging upon receipt, contact bluebird bio at 1-833-999-6378.
• Keep the infusion bag(s) in the metal cassette(s) and transfer SKYSONA from the vapor phase of liquid nitrogen shipper to the treatment center vapor phase of liquid nitrogen storage at less than or equal to -140°C (-220°F) until ready for thaw and administration.

Preparation of SKYSONA for Infusion

Coordinate the timing of SKYSONA thaw and infusion. Confirm the infusion time in advance and adjust the start time of SKYSONA thaw such that it will be available for infusion when the patient and healthcare providers are ready.

SKYSONA contains human blood cells that are genetically modified with replication-incompetent, self-inactivating Lenti-D lentiviral vector (LVV). Follow universal precautions and local biosafety guidelines for handling and disposal of SKYSONA to avoid potential transmission of infectious diseases.

1. Remove each metal cassette from liquid nitrogen storage.
2. Confirm that SKYSONA is printed on the infusion bag(s) label(s).
3. Confirm that patient identity matches the unique patient identification information located on the SKYSONA infusion bag(s). Do not infuse SKYSONA if the information on the patient-specific label on the infusion bag does not match the intended patient, and contact bluebird bio at 1-833-999-6378.
4. A SKYSONA dose may be contained in one or two patient-specific infusion bags. Ensure that the correct number of infusion bags are present. Use the accompanying Lot Information Sheet to confirm that each infusion bag is within the expiration date prior to preparation of SKYSONA for infusion.
5. Remove the overwrap and inspect each infusion bag for any breaches of integrity before thawing and infusion. If an infusion bag is compromised, follow the local guidelines and contact bluebird bio immediately at 1-833-999-6378.
6. If more than one infusion bag is provided to achieve the treatment dose, thaw and administer each infusion bag completely before proceeding to thaw the next infusion bag. Maintain the second infusion bag, if applicable, within the cold-storage dewar to maintain temperature less than or equal to -140°C (-220°F) until time to thaw.
7. Thaw SKYSONA at 37°C (98.6°F) in a water bath or dry bath. Thawing of each infusion bag takes approximately 2 to 4 minutes. Promptly remove the infusion bag from the bath once thawed. Do not leave SKYSONA unattended and do not submerge the infusion ports if thawed in a water bath.
8. After thawing, mix SKYSONA gently by massaging the infusion bag to disperse clumps of cellular material until all of the contents are uniform. If visible cell clumps remain, continue to gently mix the contents of the bag. Most small clumps of cellular material should disperse with gentle manual mixing. Do not filter, wash, spin down and/or resuspend SKYSONA in new media prior to infusion.
9. Do not sample, alter, irradiate or refreeze SKYSONA.

After SKYSONA Administration

Standard procedures for patient management after HSC transplantation should be followed after SKYSONA infusion.

• Irradiate any blood products required within the first 3 months after SKYSONA infusion.
• Patients treated with SKYSONA should not donate blood, organs, tissues, or cells at any time in the future.