Pharmaceutical particulars : מידע רוקחי

6. PHARMACEUTICAL PARTICULARS
6.1 List of excipients

Human fibrinogen syringe

Sodium citrate, dihydrate
Sodium chloride
Arginine
L-isoleucine
L-glutamic acid, monosodium
WFI (q.s.)
Human thrombin syringe

CaCl22H2O
Human albumin
Sodium chloride
Glycine
WFI (q.s.)
6.2 Incompatibilities

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.

After thawing, it can be maintained not more than 7 days at 2 °C - 8 °C or 24 hours not above 25 °C before use if it remains sealed in the original packaging.

In use shelf life: Once the blister is opened, VeraSealTM should be used immediately.

6.4 Special precautions for storage
Store and transport in a freezer (at -18 °C or colder). The cold storage chain (-18 °C or colder) must not be interrupted until use. Keep the sterilized blister in the outer carton to protect from light.

Thaw completely before use. Once thawed, do not refreeze. For storage conditions after thawing the medicinal product and after first opening, see section 6.3.

6.5 Nature and contents of container

VeraSealTM is supplied as a single-use kit containing two pre-filled syringes (glass type I) with rubber stoppers, each with a sterile frozen solution, assembled in a syringe holder.

One Dual Applicator with two additional Airless Spray Tips is supplied with the product, for application by spraying or dripping. The Airless Spray Tips are radiopaque. See scheme below.



VeraSealTM is available in the following pack sizes:
-    VeraSealTM 2 ml (containing 1 ml of human fibrinogen and 1 ml of human thrombin) -    VeraSealTM 4 ml (containing 2 ml of human fibrinogen and 2 ml of human thrombin) -    VeraSealTM 6 ml (containing 3 ml of human fibrinogen and 3 ml of human thrombin) -    VeraSealTM 10 ml (containing 5 ml of human fibrinogen and 5 ml of human thrombin) 
Not all pack sizes may be marketed.
6.6 Special precautions for disposal and other handling

An overview of thawing methods and storage after thawing is provided in Table 2.
Table 2. Thawing and storage after thawing

Thawing time per package size                  Storage after
Thawing method                                                                   thawing For 2 ml and 4 ml      For 6 ml and 10 ml
Refrigerator             Minimum 7 hours        Minimum 10 hours                 7 days at 2 - 8 °C (2 – 8 °C)                                                                       (refrigerator) in Thawing at               Minimum 70 minutes          Minimum 90 minutes          original package 20 - 25 °C                                                                       OR
24 hours not above 25 °C in original package
Sterile water bath       Minimum 5 minutes. Do       Minimum 5 minutes. Do       Use immediately (37 °C) inside sterile   not exceed 10 minutes.      not exceed 10 minutes.      during the surgery field

•       Preferred thawing methods

Refrigerator thawing
1.    Remove carton from freezer and place it in the refrigerator for thawing at 2 – 8 °C a minimum of 7 hours for the 2 ml and the 4 ml package sizes a minimum of 10 hours for the 6 ml and the 10 ml package sizes

After thawing, it is not necessary to warm the product for its use.

After thawing, the solutions must be clear to slightly opalescent and colourless to pale yellow.
Do not use solutions that are cloudy or have deposits.

Thawing at 20 ºC - 25 ºC
Remove carton from freezer, open it and take out the two blisters.
Place the blister containing the Dual Applicator on a surface at 20 ºC - 25 ºC until the fibrin sealant is ready to use.

Thaw blister with VeraSealTM pre-filled syringes at 20 ºC - 25 ºC using the following steps:

1.    Place the blister containing the syringe holder with pre-filled syringes on a surface at 20 °C - 25 °C a minimum of 70 minutes for the 2 ml and the 4 ml package sizes a minimum of 90 minutes for the 6 ml and the 10 ml package sizes


After thawing, it is not necessary to warm the product for its use.
After thawing the solutions must be clear to slightly opalescent and colourless to pale yellow. Solutions that are cloudy or have deposits should not be used.



Post-Thawing Storage
After thawing, the kit containing the VeraSealTM syringe holder with pre-filled syringes and Dual Applicator can be stored before use for not more than 7 days in the refrigerator at 2 - 8 °C or 24 hours not above 25 °C if it remains sealed in the original packaging.
Once the blisters are opened, use VeraSealTM immediately and discard any unused contents.

Once thawed, do not refreeze.

Transferring instructions
1.    After thawing, remove the blister from the surface at 20 ºC - 25 ºC or from the refrigerator at 2 °C - 8 °C.
2.    Open the blister and confirm that the VeraSealTM pre-filled syringes are completely thawed. Make the VeraSealTM syringe holder with pre-filled syringes available to a second person for transfer to the sterile field. The outside of the blister should not come in contact with the sterile field. See Figure 1.



Figure 1

•   Sterile Water Bath (Quick Thawing)

Remove carton from freezer, open it and take out the two blisters.
Place the blister containing the Dual Applicator on a surface at 20 ºC - 25 ºC until the fibrin sealant is ready to use.

Thaw VeraSealTM pre-filled syringes inside the sterile field in a sterile thermostatic water bath at a temperature of 37±2 °C using the following steps:

NOTE: Once the VeraSealTM blisters are opened, use the product immediately. Use sterile technique to avoid the possibility of contamination due to improper handling, and follow the steps below accurately. Do not remove the syringe luer cap until thawing is complete and the Dual Applicator is ready to be attached.

1.    Open the blister and make the VeraSealTM syringe holder with pre-filled syringes available to a second person for transfer to the sterile field. The outside of the blister should not come in contact with the sterile field. See Figure 1.
2.    Place the syringe holder with pre-filled syringes directly into the sterile water bath ensuring that it is completely immersed in the water. See Figure 2.
3.    At 37 °C, the time needed is approximately 5 minutes for the 2 ml, 4 ml, 6 ml, and 10 ml package sizes, but must not be left at this temperature for longer than 10 minutes.
The temperature of the water bath must not exceed 39 °C.
    4.    Dry the syringe holder with pre-filled syringes after thawing, using a sterile surgical gauze.



Figure 2

Confirm that the VeraSealTM pre-filled syringes are completely thawed. After thawing, the solutions must be clear to slightly opalescent and colorless to pale yellow. Do not use solutions that are cloudy or have deposits.

Use VeraSealTM immediately and discard any unused contents.

•   Connection instructions

1.    Open the blister and make the VeraSealTM Dual Applicator and two additional Airless Spray Tips available to a second person for transfer to the sterile field. The outside of the blister should not come in contact with the sterile field.
2.    Hold the VeraSealTM syringe holder with syringe luer caps pointed upward. See
Figure 3.
3.    Unscrew and discard the syringe luer cap of both fibrinogen and thrombin syringes.
See Figure 3.



Figure 3

4.    Hold the syringe holder with the luers pointed upward. To remove air bubbles from syringes, strike gently the side of the syringe holder one or two times while keeping the syringe holder in an upright position and lightly depress the plunger to eject air. See Figure 4.
Figure 4

5.    Attach the Dual Applicator. See Figure 5.
NOTE: Do not depress plunger during attachment or prior to intended use because the two biologic components will pre-mix in the Airless Spray Tip, forming a fibrin clot that prevents dispensing. See Figure 6.



Figure 5
Figure 6

6.    Tighten luer locks and ensure the Dual Applicator is firmly attached. The device is now ready to use.

•   Administration

Apply VeraSealTM using the syringe holder and plunger supplied.

Apply VeraSealTM using the Dual Applicator provided with the product. Other applicator tips approved by Israel Ministry of Health (IMOH) (including open surgery and laparoscopic use devices) intended for specific use with VeraSealTM may also be used.
When using the provided Dual Applicator, follow the connection instructions described above. When using other applicator tips, follow the instructions for use that are provided with the applicator tips.

Application by spraying

1.    Grasp and bend the Dual Applicator to the desired position. Tip will retain its shape.
2.    Position the Airless Spray Tip at least 2 cm away from the target tissue. Apply firm even pressure to the plunger to spray the fibrin sealant. Increase distance accordingly to achieve desired coverage of the target area.
3.    If expression is stopped for any reason, change the Airless Spray Tip prior to resuming application since a clot may form inside the Airless Spray Tip. To change the Airless Spray Tip, remove the device from the patient and unscrew the used Airless Spray Tip. See Figure 7. Place the used Airless Spray Tip away from the spare Airless Spray Tips. Wipe the end of the applicator using dry or moist sterile surgical gauze. Then, connect a new Airless Spray Tip provided in the package and ensure it is firmly connected before use.
NOTE: Red indicator will not be visible if Airless Spray Tip is properly connected.
See Figure 8.
NOTE: Do not continue pushing the plunger in an attempt to clear the fibrin clot within the Airless Spray Tip; otherwise the applicator may become unusable.
NOTE: Do not trim the Dual Applicator to avoid exposing internal wire.



Figure 7



Figure 8
Application by dripping

1.     Remove the Airless Spray Tip portion of the spray and drip tip by unscrewing the Airless Spray Tip. See Figure 7.
2.     Grasp and bend the drip tip to the desired position. Tip will retain its shape.
3.     During dripping, keep the end of the drip tip as close to the tissue surface as possible without touching the tissue during application.
4.     Apply individual drops to the surface area to be treated. To prevent uncontrolled clotting, allow the drops to separate from each other and from the end of the drip tip.
NOTE: Do not reconnect a used drip tip after it has been removed from the adapter; otherwise a clot may form inside the drip tip and the applicator may become unusable.

•     Disposal

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


7.    Marketing Authorisation Holder
OMRIX Biopharmaceuticals
Kiryat Weizmann, Nes Ziona, Israel
8. Marketing Authorisation Number

172-78-36785-00