HOLOCLAR Living tissue equivalent Ref.[49645] Active ingredients: Limbal stem cells

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.

General

Holoclar is an autologous product and should under no circumstances be administered to anyone other than the donor patient.

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).

Holoclar could contain potentially infected biological material. Although the risk is considered to be low and controlled in the manufacturing.

Precautions for use

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. When possible, concomitant eye problems should be corrected prior to Holoclar implantation.

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 antibiotics and corticosteroids (see section 4.2). For relevant safety information, physicians should consult the SmPC of these medicinal products.

No interaction studies have been performed.

Eye-drops containing benzalkonium chloride, and/or other preservatives, must be avoided. Benzalkonium chloride (as well as other quaternary ammonium compounds) is cytotoxic and eyedrops containing this preservative may damage the newly-regenerated corneal epithelium. 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.

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.

Holoclar has a major influence on the ability to drive and use machines due to the surgical nature of the underlying procedure for the implantation. Therefore, following treatment with Holoclar, driving and using machines must be limited and patients should follow the advice of their treating physician.

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 corneal epithelial instability, 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 reaction related to the surgical procedure was conjunctival haemorrhage (5%) which appears mostly during the first day after surgery and tends to be mild in intensity and disappears within a few days without treatment.

Tabulated list of adverse reactions

Adverse reactions reported in patients implanted with Holoclar 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.

Description of selected adverse reactions

Blepharitis (10.5%), and corneal epithelium defect (3.5%) were the most common individual adverse reactions not related to the surgical procedure. Glaucoma (3.5%) was the most frequent adverse reaction considered related to the corticosteroid treatment (see sections 4.2 and 4.4). Reports of glaucoma included adverse reactions of intraocular pressure.

Paediatric population

There is no information on the safety of Holoclar in children up to 7 years of age and only limited information in patients 8-17 years of age. In the paediatric patients included in the studies HLSTM01 (age 13, 14 and 16 years) and HLSTM02 (age 8 and 14 years) the profile of adverse reactions was not different from the adult population.

Elderly

There is only limited information in elderly (n=12, >65 years old) and very elderly (n=2, 75-84 years old) patients.

Reporting of suspected adverse reactions

Reporting suspected adverse reactions after authorisation of the medicinal product is important. It allows continued monitoring of the benefit/risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions via the national reporting system listed in Appendix V.

There have been no formal compatibility studies with Holoclar therefore this medicinal product should not be used with other medicinal products during the post-surgical period until the corneal epithelium integrity is fully restored. Exceptions include non-topical antibiotics for prophylaxis and corticosteroids during the immediate post-operative period.