Source: European Medicines Agency (EU) Revision Year: 2022 Publisher: Holostem Terapie Avanzate s.r.l., Via Glauco Gottardi 100, 41125 Modena, Italy Telephone: +39 059 2058070 Telefax: +39 059 2058115
Treatment of adult patients with moderate to severe limbal stem cell deficiency (defined by the presence of superficial corneal neovascularisation in at least two corneal quadrants, with central corneal involvement, and severely impaired visual acuity), unilateral or bilateral, due to physical or chemical ocular burns. A minimum of 1-2 mm² of undamaged limbus is required for biopsy.
Holoclar must be administered by an appropriately trained and qualified surgeon and is restricted to hospital use only.
This medicinal product is intended for autologous use only.
The amount of cells to be administered is dependent on the size (surface in cm²) of the corneal surface. Each preparation of Holoclar contains an individual treatment dose with sufficient number of cells to cover the entire corneal surface. The recommended dose of Holoclar is 79,000 – 316,000 cells/cm², corresponding to 1 cm² of product/cm² of defect. Each preparation of Holoclar is intended as a single treatment. The treatment may be repeated if considered indicated by the treating physician.
The administration should be followed by an appropriate antibiotic and anti-inflammatory treatment schedule, as recommended by the physician (see section 4.4).
Data on the use of Holoclar in elderly populations are limited. No recommendation on posology can be made (see sections 4.8 and 5.1).
Data on the use of Holoclar in patients with hepatic and renal impairment are not available.
The safety and efficacy of Holoclar in children and adolescents aged 0 to 18 years has not yet been established. Currently available data are described in section 4.8 and 5.1, but no recommendation on posology can be made.
For implantation.
Full technical details on the procedures associated with the use of Holoclar are provided in the educational manual.
For the manufacture of Holoclar, a biopsy of 1 – 2 mm² of undamaged limbus is required. The biopsy is performed using topical anaesthesia. The eye is subjected to ocular surface lavage with sterile balanced salt solution for eye irrigation followed by detachment of the conjunctiva from the limbus to expose the sample collection site of the cornea. An incision of 2 × 2 mm is made to remove the biopsy. The biopsy is placed in the sterile test tube supplied containing transport medium. The biopsy must be received by the manufacturer within 24 hours from the procurement.
Following the biopsy, an appropriate regimen of prophylaxis with an antibiotic treatment must be given.
In some cases, it may be possible that the source limbal stem cells of the patient are not expandable or that the release criteria are not met, due to poor biopsy quality, patient characteristics, or manufacturing failure. Therefore, it can occur that Holoclar cannot be delivered. The surgeon will be informed as early in the process as possible and should hence select an alternative treatment for the patient.
Holoclar is intended solely for use in autologous limbal stem cell regeneration in line with the approved therapeutic indication and should be administered under aseptic conditions in conjunction with limbal peritomy, undermining of the conjunctiva and excision of the corneal fibrovascular tissue in preparation of the defect bed. Next, the insert is fitted under the undermined conjunctiva. The excess of insert is trimmed, and the edge covered with the conjunctiva applying 2 or 3 stitches (sutures) of vicryl or silk 8/0 in order to form a physical seal of the lesion and to secure the implant. The eyelids are kept closed over the insert with a steri-strip band.
Holoclar is generally implanted under topical retrobulbar or parabulbar anaesthesia. Other anaesthesiology procedures may be followed at the discretion of the surgeon.
Following implantation, an appropriate regimen of topical and systemic anti-inflammatory and prophylactic antibiotic treatment must be given.
The following regimen is suggested: doxycycline 100 mg tablets twice daily (or amoxicillin 500 mg twice daily) and prednisone orally at a daily dose of 0.5 mg/kg (to a maximum dose of 25 mg) per day should be administered from the day of surgery for 2 weeks. After 2 weeks the systemic antibiotic administration should be stopped and the daily dose of prednisone should be tapered to 0.25 mg/kg (maximum 12.5 mg) per day for 1 week, to 0.125 mg/kg (maximum 5.0 mg) per day for the following week and then stopped.
Two weeks after surgery, a topical corticosteroid treatment should be started with preservative-free dexamethasone 0.1% eye-drops, 1 drop three times per day for 2 weeks, then reduced to 1 drop twice daily for 1 week and 1 drop once daily for a further week. The topical corticosteroid can be maintained in case of persistent ocular inflammation.
The implantation must be followed by an appropriate monitoring schedule.
For information on the preparation and handling of Holoclar, please refer to section 6.6.
No case of overdose has been reported.
36 hours.
Holoclar must be applied no later than 15 minutes after opening the primary container.
Store between 15°C–25°C.
Do not refrigerate or freeze.
Do not irradiate (e.g. X-rays).
Do not sterilise.
Keep the steel primary container tightly closed to protect from bacterial, fungal and viral contamination.
Holoclar is supplied as one individual treatment dose contained in a screw-cap container. Each container contains 3.8 cm² of autologous human corneal epithelium attached on a fibrin support and covered with transport medium.
The container is put in a secondary plastic container which is then put in a sealed sterile plastic bag. The sealed bag is put in a non-sterile, thermally insulated box for organ transportation with a temperature monitor. Finally, the thermally insulated box is put in a zipped sealable bag for transportation.
This medicinal product contains biological material. Healthcare professionals handling Holoclar should take appropriate precautions (wearing gloves, protective clothing and eye protection) to avoid potential transmission of infectious diseases.
Holoclar is intended solely for autologous use. Prior to implantation the patient’s identity should be carefully checked with the patient/donor identification on the shipment documentation and product container.
Any shaking, inverting or other mechanical stress of the Holoclar container should be avoided.
Holoclar must not be sterilised. The container and closure should be carefully visually inspected for any damage. If the Holoclar primary container is damaged, the visual appearance of the product is affected, and/or visual particulates are identified, the product must not be used and must be returned to the manufacturer. If the temperature monitored in the insulated box deviates from the storage conditions, contact the manufacturer.
See the educational material for further information.
The medicinal product contains potentially infected biological material. Local guidelines on handling human-derived material should be followed for unused medicinal products or waste material. All material that has been in contact with Holoclar (solid and liquid waste) should be handled and disposed of as potentially infectious waste in accordance with local guidelines on handling humanderived material.
Accidental exposure to Holoclar must be avoided. Local guidelines on handling of human derived materials should be followed in case of accidental exposure, which may include washing of the contaminated skin and removal of contaminated clothes. Work surfaces and materials which have potentially been in contact with Holoclar must be decontaminated with appropriate disinfectant.
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