ALOFISEL Suspension for injection Ref.[8682] Active ingredients: Darvadstrocel

Alofisel should only be administered by specialist physicians experienced in the diagnosis and treatment of conditions for which Alofisel is indicated.

Posology

A single dose of Alofisel consists of 120 million cells supplied in 4 vials. Each vial contains 30 million cells in 6 mL of suspension. The full content of the 4 vials must be administered for the treatment of up to two internal openings and up to three external openings. This means that with a dose of 120 million cells it is possible to treat up to three fistula tracts that open to the perianal area.

The efficacy or safety of repeat administration of Alofisel has not been established.

Special populations

Elderly

Data on the use of darvadstrocel in the elderly population are limited, however, given the cell-based nature of darvadstrocel and its local administration route it is not expected that the benefit-risk profile of darvadstrocel in elderly patients will differ from that observed in non-elderly patients. Therefore, no dose adjustment is required in elderly patients.

Hepatic or renal impairment

Data on the use of darvadstrocel in patients with hepatic or renal impairment are not available, however, given the cell-based nature of darvadstrocel and its local administration route it is not expected that the benefit-risk profile of darvadstrocel in hepatically or renally impaired patients will differ from that observed in non-hepatically or non-renally impaired patients. Therefore, no dose adjustment is required in hepatically or renally impaired patients.

Paediatric population

The safety and efficacy of darvadstrocel in children and adolescents aged 0 to 17 years have not yet been established. No data are available.

Method of administration

For injection in the fistula tract tissue in a surgical environment under anaesthesia (general or regional (see section 4.4)) as described below. In line with standards for the management of complex perianal fistulas, characterisation of the patient’s fistulas is needed prior to treatment. It is recommended that at least 2 to 3 weeks before the administration day, preparatory surgery is performed comprising exploration (under anaesthesia) of fistula anatomy (number of existing fistulas and openings), topography (extent and relationship with the sphincters and other pelvic muscles), potential associated complications (such as abscesses) and whether local mucosal disease is mild or inactive. Vigorous curettage of all fistula tracts is recommended, with special emphasis in the internal openings area, using a metallic curette. In case of an abscess, incision and drainage are needed, and setons should be placed, if appropriate, in accordance with routine surgical procedures. Before scheduling Alofisel administration, the surgeon must ensure that no abscesses are present.

Immediately prior to the administration of Alofisel, the fistula tracts should be conditioned as follows:

• If setons are in place, they must be removed.
• Identify the location of the internal openings. For this, injection of a sodium chloride 9 mg/mL (0.9%) solution through the external openings until it gets out through the internal openings is recommended. The injection of any other substance through the fistula tracts, such as hydrogen peroxide, methylene blue, iodine solutions or hypertonic glucose solutions is not allowed, as these agents compromise the viability of the cells to be injected (see section 4.4 and section 4.5).
• Perform a vigorous curettage of all fistula tracts, with special emphasis in the internal openings areas, using a metallic curette.
• Suture closed the internal openings.

After conditioning of the fistula tracts, Alofisel should be administered according to the following two steps:

1. Preparation

• a) The expiry time: date of Alofisel should be re-confirmed; vials should then be removed from the outer packaging.
• b) Re-suspend the cells by gently tapping the bottom of the vials until a homogeneous suspension is obtained, avoiding bubble formation. Each vial should be used immediately after re-suspension to prevent the cells from re-sedimenting.
• c) Remove the cap from the vial, gently turn the vial upside down, and gently aspirate the whole content using a syringe with a conventional needle no thinner than 22G (see section 4.4).
• d) Replace the needle with a longer needle, also no thinner than 22G, in order to reach the intended sites of injection. For example, a needle for spinal anaesthesia measuring around 90 mm in length is required.
• e) Repeat steps (b), (c) and (d) for each of the vials in turn after the cells from one vial have been injected.

2. Injection

Two of the vials should be used for the internal openings and the remaining two for injection along the walls of the fistula tracts (via external openings). After inserting the needle tip into each intended injection site, perform a slight aspiration to avoid intravascular administration.

• a) Injection around the internal openings of the fistulas tracts: insert the needle through the anus and proceed as follows:
  • If there is a single internal opening, inject the content of each of the two vials (one after the other) in small deposits into the tissue surrounding the single internal opening.
  • If there are two internal openings, inject the content of the first of two vials in small deposits into the tissue around one internal opening. Then inject the content of the second vial in small deposits into the tissue around the second internal opening.
• b) Injection along the walls of the fistula tracts: insert the needle through the external openings and, from within the fistulas lumen:
  • If there is a single external opening, inject separately the content of each of the remaining two vials superficially into the tissue walls along the length of the fistula tracts, making small deposits of the cell suspension.
  • If there are two or three external openings, inject the content of the remaining two vials equally between the associated tracts. The procedure for injection along the walls of the fistula tracts should be performed based on prior knowledge of the anatomy and topology of the fistula tracts, as determined during the fistulas characterisation. Ensure cells are not injected into the lumen of the fistula tracts to avoid leakage of cells.

Softly massage the area around the external openings for 20–30 seconds and cover the external openings with a sterile bandage.

No case of overdose has been reported.

Shelf life: 72 hours.

Store between 15ºC and 25ºC.

Keep the product within the outer carton and inside the shipping container at all times until its administration, to maintain the required temperature. Preserve the container away from heat and direct light sources and do not refrigerate or freeze.

Do not irradiate or otherwise sterilise.

Alofisel is supplied as one treatment dose contained in 4 Type I glass vials. Each vial contains 6 mL of eASC suspension and is closed with a rubber stopper and a flip-off seal. The vials are placed inside a cardboard box.

Alofisel must not be filtered or administered using a needle thinner than 22G (see section 4.4).

Immediately before use, Alofisel must be re-suspended by gently tapping the bottom of the vial until a homogeneous suspension is obtained, avoiding bubble formation. For further information on the use of Alofisel see section 4.2.

Any unused product or waste material should be disposed of in accordance with local requirements.