Intravenous administration of ofatumumab to pregnant cynomolgus monkeys at 100 mg/kg once weekly from days 20 to 50 of gestation did not elicit maternal or foetal toxicity or teratogenicity. At day 100 of gestation, depletion of B-cells relating to the pharmacological activity of ofatumumab were observed in foetal cord blood and foetal splenic tissues. Pre- and post-natal development studies have not been performed. Post-natal recovery has therefore not been demonstrated.

As ofatumumab is a monoclonal antibody, genotoxicity and carcinogenicity studies have not been conducted with ofatumumab.

6. PHARMACEUTICAL PARTICULARS

6.1 List of excipients

 Arginine

Sodium acetate (E262)

Sodium chloride

Polysorbate 80 (E433)

Edetate disodium (E386)

Hydrochloric acid (E507) (for pH-adjustment)

Water for injections

6.2 Incompatibilities

 This medicinal product must not be mixed with other medicinal products except those mentioned in section 6.6.

6.3 Shelf life

 Vial

2 years.

Diluted infusion

Chemical and physical in-use stability has been demonstrated for 48 hours at ambient conditions (less than 25 °C).

From a microbiological point of view, the product should be used immediately. If not used immediately, in-use storage times and conditions prior to use are the responsibility of the user and would normally not be longer than 24 hours at 2-8 ºC, unless reconstitution/dilution has taken place in controlled and validated aseptic conditions.

6.4 Special precautions for storage

 Store and transport refrigerated (2°C – 8°C).

Do not freeze.

Keep the vial in the outer carton in order to protect from light.

For storage conditions of the diluted medicinal product, see section 6.3.

6.5 Nature and contents of container

 Clear Type I glass vial with a latex-free bromobutyl rubber stopper and aluminium over-seal, containing 50 ml of concentrate for solution for infusion.

Arzerra is available in 1 vial packs and it is supplied with two extension sets.

6.6 Special precautions for disposal and other handling

 Arzerra concentrate for solution for infusion does not contain a preservative; therefore dilution should be carried out under aseptic conditions. The diluted solution for infusion must be used within 24 hours of preparation. Any unused solution remaining after this time should be discarded.

• Before diluting Arzerra

Check the Arzerra concentrate for particulate matter and discoloration prior to dilution. Ofatumumab should be a colourless solution. Do not use the Arzerra concentrate if there is discolouration.

Do not shake the ofatumumab vial for this inspection.

The concentrate may contain a small amount of visible translucent-to-white, amorphous, ofatumumab particles. The filters provided as part of the extension set will remove these particles.

• How to dilute the solution for infusion

The Arzerra concentrate must be diluted in sodium chloride 9 mg/ml (0.9%) solution for injection prior to administration, using aseptic technique.

2,000 mg dose - Use 2 vials (100 ml total, 50 ml per vial):

- w