Rethymic Dosage

Preparation for the Implantation Procedure:

1. Operating room culture dishes (sterile 100 mm tissue culture dishes) and saline for injection are supplied by the operating room; a sufficient supply of operating room culture dishes and saline must be provided by the hospital for use in the implantation procedure.
2. The product is delivered to the operating room by manufacturing personnel. The recommended dose is determined based on the patient's BSA. The manufacturer calculates the dose in advance for the specific patient. Manufacturing personnel and the operating room staff confirm that the lot delivered is for the intended recipient.
3. Manufacturing personnel communicate to the surgical team the minimum number of RETHYMIC slices to be implanted to achieve the minimum dose. The product expiration date and time for the entire lot is labeled on each polystyrene dish (drug product dish).
4. Always handle RETHYMIC slices aseptically. Do not use if there is evidence of contamination.
5. Outside the sterile field, manufacturing personnel unpack RETHYMIC from the shipping box. One drug product dish at a time is removed from the drug product box and shipping box. Manufacturing personnel inspect the drug product box and each drug product dish for signs of contamination, damage, spills, or leakage. If damage to the drug product dishes, leaks, spillage or evidence of contamination is noted, manufacturing personnel will notify the surgical team that the lot cannot be implanted.
6. When the surgical team is ready, manufacturing personnel and surgical staff begin the transfer of drug product to the sterile operative field. Manufacturing personnel carry one drug product dish, which contains up to 4 RETHYMIC slices on up to 2 surgical sponges, with each RETHYMIC slice on a filter membrane, to the surgical staff near the sterile field. Manufacturing personnel open the drug product dish to expose the RETHYMIC slices.
7. The surgical staff team member uses a pair of forceps to remove individual RETHYMIC slices with their filter membranes from the drug product dish (Figure 1). The surgical team member places each RETHYMIC slice with its filter membrane into a sterile 100 mm tissue culture dish ("operating room culture dish") containing approximately 2 mL preservative-free saline that resides in the sterile field on the instrument table. This is repeated to transfer all RETHYMIC slices from the first drug product dish into a sterile operating room culture dish. After the first set of RETHYMIC slices has been prepared for surgical implantation and provided to the surgeon, another drug product dish with RETHYMIC slices is passed to the surgical staff member for removal from their filter membranes as described above.
8. Using 2 pairs of sterile forceps, the surgical staff team member should use one pair of forceps to hold the filter in place while using the other forceps to scrape and loosen the RETHYMIC slice from the filter membrane (Figure 1). Then, while using one pair of forceps to hold the filter in place, the surgical staff team member uses the other forceps to lift the RETHYMIC slice away from the filter membrane by pulling the tissue up. The surgical staff team member places each RETHYMIC slice separately into the saline-containing operating room culture dish in the sterile field on top of its original filter membrane. The RETHYMIC slice will change from a flatter slice to a condensed, lumpy shape at this stage of the procedure. The surgeon then implants the first set of RETHYMIC slices. The surgical team staff member should process the next set of up to 4 RETHYMIC slices from the next drug product dish into a second operating room culture dish in the same manner while the surgeon continues implanting the first set of up to 4 slices. When the surgeon finishes implanting the first set of RETHYMIC slices, the surgical staff team member transfers and prepares the next operating room culture dish on the surgical field. Continue this cycle until all the desired tissue is transferred during the implantation procedure.

Figure 1: Preparing for the Implantation Procedure

Figure 1: Within the sterile field, forceps are used to move individual RETHYMIC slices with their filter membranes from the drug product dish to the operating room culture dish (left images). A pair of forceps is used to gently scrape and lift the RETHYMIC slice off the filter membrane in the operating room culture dish in preparation for easy removal prior to implantation (right images).

Implantation of RETHYMIC:

• After induction of general anesthesia, a cranial-caudal skin incision (typically ~5 cm in length; Figure 2) should be made over the anterior thigh compartment. The size of the incision and the use of one or both legs for the implantation procedure is determined by the size of the patient, his/her muscle mass, and the amount of tissue to be implanted. If all or nearly all of the tissue can be implanted in one leg, then only one leg should be used.

Figure 2: Surgical Incision and Opening of Fascia

• Open fascia to expose the anterior compartment muscles (Figure 2).
• Create a pocket in between the muscle fibers using a tonsil clamp or similar instrument. Each pocket should be made along the natural furrows throughout the quadriceps muscle group.
• Individual RETHYMIC slices should be implanted approximately 1 cm in depth and approximately 1 cm apart into the pockets between the muscle fibers in the quadriceps muscle (Figure 3).

Figure 3: Implant Individual RETHYMIC Slices

• A large or thick RETHYMIC slice may be cut in half, at the surgeon's discretion, to ensure the slice is surrounded by muscle tissue once implanted. Implant as many RETHYMIC slices as possible within the recommended dose range of 5,000 to 22,000 mm2 of processed thymus tissue/m2 recipient BSA. During the procedure, the surgeon uses their judgment to balance the benefit of implanting additional RETHYMIC slices against the risk(s) that may be associated with implantation into limited muscle mass, number of implantations sites and other patient considerations.
• Once each RETHYMIC slice has been implanted, it should be fully covered by muscle tissue. Then a single absorbable suture should be used to close the pocket where the RETHYMIC slice was implanted (Figure 4).

Figure 4: Close the Site of Implantation

• Once the intended dose has been implanted, confirm hemostasis. Close the skin incision with 2 layers of absorbable sutures and apply a standard dressing, such as wound closure strips or skin glue. Leave the fascia open to allow room for muscle compartment swelling. An occlusive dressing may be used to prevent contamination.