Pharmaceutical particulars : מידע רוקחי

6.     PHARMACEUTICAL PARTICULARS

6.1    List of excipients
Brineura solution for infusion and flushing solution
Sodium chloride
Water for injections
Potassium chloride
Calcium chloride dihydrate
Magnesium chloride hexahydrate
Sodium phosphate dibasic heptahydrate
Monobasic sodium phosphate monohydrate


6.2   Incompatibilities
In the absence of compatibility studies, this medicinal product must not be mixed with other medicinal products.

6.3   Shelf life

The expiry date of the product is indicated on the packaging materials.
Thawed Brineura and flushing solution should be used immediately. The medicinal product should only be withdrawn from the unopened vials immediately prior to use. If immediate use is not possible, unopened vials of Brineura or flushing solution should be stored in a refrigerator (2°C - 8°C) and used within 24 hours.

Chemical and physical in-use stability has been demonstrated for up to 12 hours at room temperature (19°C - 25°C). From a microbiological point of view, open vials or medicinal product held in syringes should be used immediately. If not used immediately, in-use storage times and conditions prior to use are the responsibility of the user.

6.4   Special precautions for storage

Store upright in a freezer (-20°C ± 5°C).
Store in the original package in order to protect from light.
6.5   Nature and contents of container

Vial (type I glass) with a stopper (butyl rubber), a flip-off cap (polypropylene) and crimp seal (aluminium).
Brineura has a green flip-off cap and flushing solution has a yellow flip-off cap.

Pack size :
Each pack contains two vials, each containing 150 mg of cerliponase alfa in 5 ml of solution for infusion and one vial containing 5 mlof flushing solution.

6.6   Special precautions for disposal and other handling

Brineura should be administered with infusion components shown to be chemically and physically compatible with administration of Brineura and flushing solution.

Brineura is compatible with intracerebroventricular access devices made of a silicone dome with a stainless steel or polypropylene base that is attached to a silicone catheter.

Brineura is compatible with disposable infusion components made of PVC, PVC (non-DEHP) polyethylene, polyethersulfone (PES), polypropylene (PP), and PTFE.

Preparation for administration of Brineura and flushing solution

The following components (not supplied) are required for proper administration of Brineura and flushing solution (see Figure 1 in section 4.2). All infusion components must be sterile. Brineura and flushing solution are supplied and stored frozen (see section 6.4).

•     A programmable syringe pump with appropriate delivery range, delivery rate accuracy, and alarms for incorrect delivery or occlusion. The pump must be programmable to deliver the medicinal product at a constant rate of 2.5 ml/hr.
•     Two single-use syringes compatible with the pump equipment. A syringe volume of 10 to 20 ml is recommended.
•     Two single-use hypodermic syringe needles, (21 G, 25.4 mm).
•     One single-use infusion set. An extension line may be added if needed. A length of 150 cm to 206 cm (not to exceed 400 cm) and an inner diameter of 0.1 cm is recommended.
•     A 0.2 µm inline filter is required. The inline filter may be integral to the infusion set. The inline filter should be placed as close as practically possible to the port needle.
•     A non-coring port needle with a gauge of 22 or smaller and a suggested length of 16 mm. Refer to the intracerebroventricular access device manufacturer’s recommendation for the port needle.
•     One empty sterile single-use syringe (for collection of CSF to check patency).

Thaw Brineura and flushing solution

Thaw Brineura vials and flushing solution vial at room temperature for approximately 60 minutes. Do not thaw or warm vials any other way. Do not shake vials. Condensation will occur during thawing period.
Thawing the vials outside the carton is recommended.

Brineura and flushing solution must be completely thawed and used immediately (see section 6.3).

Do not re-freeze vials or freeze syringes containing Brineura or flushing solution.
Inspect thawed Brineura and flushing solution vials

Inspect the vials to ensure they are fully thawed. Brineura solution should be clear to slightly opalescent and colourless to pale yellow. Brineura vials may occasionally contain thin translucent fibres or opaque particles.
These naturally occurring particles are cerliponase alfa. These particles are removed via the 0.2 μm inline filter without having a detectable effect on the purity or strength of Brineura.

The flushing solution may contain particles that dissolve when the vial is fully thawed. The flushing solution should be clear and colourless.

Do not use if the solutions are discoloured or if there is other foreign particulate matter in the solutions.

Withdraw Brineura
Label one unused sterile syringe “Brineura” and attach a syringe needle. Remove the green flip-off caps from both Brineura vials. Using aseptic technique, withdraw the volume of Brineura solution per required dose (see Table 1 in section 4.2) into the sterile syringe labelled “Brineura”. Do not dilute Brineura. Do not mix Brineura with any other medicinal product. Discard the needle and empty vials per local requirements.

Withdraw flushing solution

Determine the volume of flushing solution needed to ensure complete delivery of Brineura to the cerebral ventricles. Calculate the flush volume by adding the priming volume of all infusion components, including the intracerebroventricular access device.

Label one unused sterile syringe “flushing solution” and attach a syringe needle. Remove the yellow flip-off cap from the flushing solution vial. Using aseptic technique, withdraw the appropriate amount of flushing solution from the vial into the new sterile syringe labelled “flushing solution”. Discard the needle and the vial with the remaining solution per local requirements.

Disposal

Any unused medicinal product or waste material should be disposed of in accordance with local requirements.