Mobilization and Apheresis

Patients are required to undergo HSC mobilization followed by apheresis to obtain CD34+ cells for product manufacturing.

The target number of CD34+ cells to be collected is ≥ 12 × 106 CD34+ cells/kg. If the minimum dose of 5.0 × 106 CD34+ cells/kg is not met, the patient may undergo additional cycles of mobilization and apheresis, separated by at least 14 days, in order to obtain more cells for additional manufacture. Up to two drug product lots may be administered to meet the target dose.

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. These cells must be collected from the patient and be cryopreserved prior to myeloablative conditioning. The back-up collection may be needed for rescue treatment if there is: 1) compromise of hematopoietic stem cells or ZYNTEGLO before infusion, 2) primary engraftment failure, or 3) loss of engraftment after infusion with ZYNTEGLO.

Myeloablative Conditioning

Full myeloablative conditioning must be administered before infusion of ZYNTEGLO. Consult prescribing information for the myeloablative conditioning agent(s) prior to treatment.

Stop iron chelation at least 7 days prior to myeloablative conditioning. Prophylaxis for hepatic veno-occlusive disease (VOD) is recommended [see Clinical Studies (14)]. Prophylaxis for seizures should be considered, as appropriate.

Do not begin myeloablative conditioning until the complete set of infusion bag(s) constituting the dose of ZYNTEGLO has been received and stored at the treatment center and the availability of the back-up collection is confirmed. After completion of the myeloablative conditioning, allow a minimum of 48 hours of washout before ZYNTEGLO infusion.

Receipt and Storage of ZYNTEGLO

• ZYNTEGLO is shipped to the treatment center in the vapor phase of liquid nitrogen shipper.
• Confirm patient identifiers on the product label(s) 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 ZYNTEGLO from the vapor phase of liquid nitrogen shipper to the treatment center vapor phase of liquid nitrogen storage at ≤ -140°C (≤ -220°F). Store in the vapor phase of liquid nitrogen at ≤ -140°C (≤ -220°F) until ready for thaw and administration.

Preparation of ZYNTEGLO for Infusion

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

1.

Remove each metal cassette from liquid nitrogen storage and remove each infusion bag from the metal cassette.

2.

Confirm that ZYNTEGLO is printed on the infusion bag(s).

3.

Confirm that patient identity matches the unique patient identifiers located on the ZYNTEGLO infusion bag(s). Do not infuse ZYNTEGLO 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.

Ensure 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.

5.

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, thaw and administer each infusion bag completely before proceeding to thaw the next infusion bag.

7.

Thaw ZYNTEGLO at 37°C (98.6°F) in a water bath or dry bath. Thawing of each infusion bag takes approximately 2 to 4 minutes. Do not leave ZYNTEGLO unattended. Do not submerge the infusion ports in a water bath.

8.

After thaw, mix the contents 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 ZYNTEGLO in new media prior to infusion.

9.

Do not sample, alter, irradiate or refreeze ZYNTEGLO.

After ZYNTEGLO Administration

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

• Irradiate any blood products required within the first 3 months after ZYNTEGLO infusion.
• Granulocyte-colony stimulating factor (G-CSF) is not recommended for 21 days after ZYNTEGLO infusion.
• Restarting iron chelation after ZYNTEGLO infusion may be necessary and should be based on clinical practice [see Drug Interactions (7.3) and Clinical Studies (14)]. Phlebotomy can be used in lieu of iron chelation, when appropriate.
• Patients should not donate blood, organs, tissues, or cells at any time in the future.

ZYNTEGLO contains human blood cells that are genetically modified with replication-incompetent, self-inactivating lentiviral vector. Follow universal precautions and biosafety guidelines (Biosafety Level 2) for handling and disposal of ZYNTEGLO to avoid potential transmission of infectious diseases.