nship was established between average plasma concentration of certolizumab pegol during a dosing interval (Cavg) and efficacy (ACR 20 responder definition). The typical Cavg that produces half the maximum probability of ACR 20 response (EC50) was 17 µg/ml (95% CI: 10-23 µg/ml).
5.3 Preclinical safety data
The pivotal non-clinical safety studies were conducted in the cynomolgus monkey. In rats and monkeys, at doses higher than those given to humans, histopathology revealed cellular vacuolation, present mainly in macrophages, in a number of organs (lymph nodes, injection sites, spleen, adrenal, uterine, cervix, choroid plexus of the brain, and in the epithelial cells of the choroid plexus). It is likely that this finding was caused by cellular uptake of the PEG moiety. In vitro functional studies of human vacuolated macrophages indicated all functions tested were retained. Studies in rats indicated that >90% of the administered PEG was eliminated in 3 months following a single dose, with the urine being the main route of excretion.
Certolizumab pegol does not cross-react with rodent TNF. Therefore, reproductive toxicology studies have been performed with a homologous reagent recognising rat TNF. The value of these data to the eva luation of human risk may be limited. No adverse effects were seen on maternal well-being or female fertility, embryo-foetal and peri- and post-natal reproductive indices in rats using a rodent anti-rat TNFα PEGylated Fab' (cTN3 PF) following sustained TNFα suppression. In male rats, reduced sperm motility and a trend of reduced sperm count were observed.
Distribution studies have demonstrated that placental and milk transfer of cTN3 PF to the foetal and neonatal circulation is negligible. It is presently unknown whether the same is true for Cimzia in humans.
No mutagenic or clastogenic effects were demonstrated in preclinical studies. Carcinogenicity studies have not been performed with Cimzia.
6. PHARMACEUTICAL PARTICULARS
6.1 List of excipients
Sodium acetate
Sodium chloride
Water for injections
6.2 Incompatibilities
In the absence of compatibility studies, this medicinal product must not be mixed with other medicinal products.
6.3 Shelf life
18 months.
6.4 Special precautions for storage
Store in a refrigerator (2°C – 8°C).
Do not freeze.
Keep the pre-filled syringe in the outer carton in order to protect from light.
6.5 Nature and contents of container
One ml pre-filled syringe (type I glass) with a plunger stopper (bromobutyl rubber), containing 200 mg of certolizumab pegol.
None of the components of the syringe contain latex.
Pack size of 2 syringes and 2 alcohol wipes, and multipack containing 6 (3 packs of 2) pre-filled syringes and 6 (3 packs of 2) alcohol wipes.
Not all pack sizes may be marketed.
6.6 Special precautions for disposal and other handling
This medicinal product is for single use only.
Any unused product or waste material should be disposed of in accordance with local requirements.
Comprehensive instructions for the preparation and administration of Cimzia in a pre-filled syringe are given in the package leaflet.
7. MARKETING AUTHORISATION HOLDER
UCB Pharma SA
Allée de la Recherche 60
B-1070 Bruxelles
Belgium
8. MARKETING AUTHORISATION NUMBER(S)
EU/1/09/544/001-002
9. DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION
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