Holoclar

HOS-155503 · has-adverse-reaction-information · PDF-Seite 5

5 Summary of the safety profile The most serious adverse reactions are corneal perforation and ulcerative keratitis, which may occur within the 3 months from Holoclar implantation and are related to the poor corneal stem cell engraftment, and syncope vasovagal occurring in the first day after surgery due to eye pain. The most common adverse reactions are eye disorders. The most frequently occurring reactions related to the surgical procedure were eye pain (4.0 %), corneal epithelium defect (3.4 %) and conjunctival haemorrhage (2.2 %), the latter appearing mostly during the first day after surgery and in most cases to be mild in intensity and disappearing within a few days without treatment. Tabulated list of adverse reactions Adverse reactions reported in patients implanted with Holoclar in clinical studies and post-marketing experience are provided in the table. The following categories are used to rank the adverse reactions by frequency of occurrence: very common (≥1/10), common (≥1/100 to <1/10), uncommon (≥1/1 000 to <1/100), rare (≥1/10 000 to <1/1 000), very rare (<1/10 000) and not known (cannot be estimated from the available data). Within each frequency grouping the adverse reactions are presented in the order of decreasing seriousness. MedDRA System organ class Adverse reaction Frequency Infections and infestations Corneal infection, conjunctivitis Uncommon Nervous system disorders Syncope vasovagal, headache Uncommon Conjunctival haemorrhage, eye haemorrhage, corneal epithelium defect, corneal abrasion/erosion, Common glaucoma/intraocular pressure increased, keratitis/ulcerative keratitis, blepharitis, eye pain Eye disorders Conjunctival adhesion, conjunctival granuloma, conjunctival hyperaemia, corneal oedema, corneal perforation, corneal thinning, corneal opacity, corneal Uncommon hypertrophy, eye inflammation, hyphaemia, eye irritation, photop

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HOS-155499 · has-contraindication-information · PDF-Seite 4

Hypersensitivity to any of the excipients listed in section 6.1 or to bovine serum and murine 3T3-J2 cells.

HOS-155498 · has-indication-information · PDF-Seite 2

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.

HOS-155501 · has-interaction-information · PDF-Seite 5

No interaction studies have been performed. The concomitant use of topical lidocaine or anaesthetics containing adrenaline must be avoided as they reduce the colony forming efficiency. Eye-drops containing benzalkonium chloride, and/or other preservatives, must be avoided. Benzalkonium chloride (as well as other quaternary ammonium compounds) is cytotoxic and eye- drops containing this preservative may damage the corneal epithelium, in particular the proliferative basal layer, exposed during the implantation procedure. Other cytotoxic agents must be avoided. No interactions between Holoclar and the post-biopsy/post-operative treatment suggested in section 4.2 have been reported.

HOS-155502 · has-pregnancy-information · PDF-Seite 5

Pregnancy There are no data for the use of Holoclar in pregnant women. Animal studies are not available with respect to reproductive toxicity (see section 5.3). As a precautionary measure, and in light of the requirement of the post-operative pharmacological treatment, it is preferable to avoid the use of Holoclar during pregnancy. Breast-feeding As a precautionary measure, Holoclar is not recommended for implant during breast-feeding. Fertility No clinical data on the effects of Holoclar on fertility are available.

HOS-155500 · has-warning-information · PDF-Seite 4

Traceability The traceability requirements of cell-based advanced therapy medicinal products must apply. To ensure traceability the name of the product, the batch number and the name of the treated patient should be kept for a period of 30 years after expiry date of the product. Autologous use Holoclar is intended solely for autologous use and must not, under any circumstances, be administered to other patients. Holoclar must not be administered if the information on the product labels and lot number do not match the patient’s identity. Hypersensitivity reactions Holoclar contains lethally-irradiated murine 3T3 fibroblast cells and may contain traces of foetal bovine serum. Patients with a known hypersensitivity to mice or foetal bovine serum must not be treated (see section 4.3). Transmission of an infectious agent Holoclar could contain potentially infected biological material. Although Holoclar is tested for sterility and mycoplasma, a risk of transmission of infectious agents exists. Healthcare professionals administering Holoclar must, therefore, monitor patients for signs and symptoms of infections after treatment and treat appropriately, if needed. Precautions for use A thorough evaluation of the patient should be done taking into consideration not only the clinical need of the candidate, but also the biological and pathophysiologic alterations in the wound bed environment, to define the timing of any procedure and allow the proper engraftment and growth of the stem cells of the living tissue that constitute Holoclar. Concomitant surgeries should be excluded and anticipated or deferred to Holoclar implantation. 4 Concomitant eyelids malposition, conjunctival scarring with fornix shortening, corneal anaesthesia and/or conjunctival anaesthesia or severe hypoaesthesia, pterygium and severe dry eye are potential complicating factors. Concomitant eye problems should be corrected prior to Holoclar implantation. At any of the steps of the treatment with Holoclar, topical lidocaine or anaesthetics containing adrenaline must be avoided. Patients with acute ocular inflammation or infections should be deferred until recovery has been documented since inflammation may compromise treatment success. Concomitant use of Holoclar with eye-drops containing benzalkonium chloride, and/or other preservatives is not recommended (see section 4.5). The procedure of Holoclar administration includes the use of ant

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