Tisseel

FOR TOPICAL USE ONLY – DO NOT INJECT.

The required dose of TISSEEL depends on the size of the surface to be covered. The approximate surface areas covered by each package size of TISSEEL are listed in the following table:

Table 1 Maximum size of the area to be sealed using cannula Maximum size of the area to be sealed using compressed gas Required package size of TISSEEL 8 cm2 100 cm2 2 mL 16 cm2 200 cm2 4 mL 40 cm2 500 cm2 10 mL

It is recommended that every time a patient receives a dose of TISSEEL, the name and batch number of the product are documented in order to maintain a record of the batches used.

2.1 Preparation of TISSEEL Kit (Freeze-Dried)

During preparation of TISSEEL Kit:

DO NOT EXPOSE TO TEMPERATURES ABOVE 37°C

DO NOT MICROWAVE
DO NOT REFRIGERATE OR FREEZE AFTER RECONSTITUTION

Do not use iodine or heavy metal containing preparations such as betadine for disinfection of vial stoppers. Allow alcohol-based disinfectants to evaporate before puncturing stopper.

Use separate syringes for reconstituting Sealer Protein and Thrombin solutions and for application to prevent premature clotting.

After reconstitution, the product must be used within 4 hours.

TISSEEL Kit contains the following substances in four separate vials:

-Sealer Protein Concentrate (Human)

-Fibrinolysis Inhibitor Solution (Synthetic)

-Thrombin (Human)

-Calcium Chloride Solution

Freeze-dried Sealer Protein Concentrate and Thrombin are reconstituted in Fibrinolysis Inhibitor Solution and Calcium Chloride Solution, respectively. The Sealer Protein Solution and Thrombin Solution are then combined using the DUPLOJECT Preparation and Application System, or an equivalent delivery device cleared by FDA for use with TISSEEL, to form the Fibrin Sealant.

Prewarming TISSEEL Kit with FIBRINOTHERM

If a FIBRINOTHERM device is not available, contact Baxter (1-800-423-2090) for assistance. See FIBRINOTHERM manual for complete operating instructions.

Plug the FIBRINOTHERM Heating and Stirring Device into an electrical socket and activate the warmer (amber switch). Ensure that the stirring mechanism of the FIBRINOTHERM device is initially switched off (green switch). Place all four vials from the TISSEEL Kit into the prewarmed wells of the FIBRINOTHERM, using the appropriately sized adapter rings, and allow the vials to warm for up to 5 minutes (room temperature product may take less time).

Preparation of Sealer Protein Solution with FIBRINOTHERM

Remove the flip-off caps from the vial containing the Sealer Protein Concentrate and the vial containing the Fibrinolysis Inhibitor Solution, disinfect the rubber stoppers of both vials with a germicidal solution and allow to dry. Transfer the Fibrinolysis Inhibitor Solution into the vial containing the freeze-dried Sealer Protein Concentrate using the sterile reconstitution components provided with the DUPLOJECT Preparation and Application System, or an equivalent device cleared by FDA for use with TISSEEL (see directions provided with the device system for specific reconstitution instructions). Gently swirl the vial to ensure that the freeze-dried material is completely soaked. Place the vial into the largest opening of the FIBRINOTHERM device with the appropriate adaptor. Switch on the stirrer (green switch) and allow the vial contents to stir until all Sealer Protein Concentrate is dissolved. Reconstitution of the freeze-dried Sealer Protein Concentrate is complete as soon as no undissolved particles are visible. Otherwise, return the vial to the FIBRINOTHERM device and agitate for a few more minutes until the solution appears homogeneous.

Notes:

-Do not use the Sealer Protein Concentrate until it has fully dissolved. If the Sealer Protein Concentrate has not dissolved within 20 minutes using the FIBRINOTHERM device, discard the vial and prepare a fresh kit.

-If not used promptly, keep the Sealer Protein Solution at 37°C without stirring. To ensure homogeneity, switch on the stirrer of the FIBRINOTHERM device shortly before drawing up the solution.

Preparation of Thrombin Solution with FIBRINOTHERM

Remove the flip-off caps from the vial containing Thrombin and the vial containing Calcium Chloride Solution, disinfect the rubber stoppers of both vials with a germicidal solution and allow to dry. Transfer the contents of the vial with Calcium Chloride Solution into the vial containing the freeze-dried Thrombin using the sterile reconstitution components provided with the DUPLOJECT Preparation and Application System, or an equivalent device cleared by FDA for use with TISSEEL (see directions provided with the device system for specific reconstitution instructions). Swirl briefly. Place the vial into the adapted opening of the FIBRINOTHERM device. Reconstitution of Thrombin is complete when all of the Thrombin concentrate is dissolved. Keep the Thrombin Solution at 37°C until used.

Transferring to the Sterile Field

For transfer of the Sealer Protein Solution and the Thrombin Solution to the sterile field, the scrub nurse should withdraw the solutions while the circulating nurse holds the non-sterile vials. The solutions should be withdrawn slowly by firm constant aspiration to reduce the risk of large air bubbles.

See DOSAGE AND ADMINISTRATION, Method of Application (2.3).

2.2 Preparation of TISSEEL Pre-Filled Syringe (Frozen)

During preparation of TISSEEL (frozen):

DO NOT EXPOSE TO TEMPERATURES ABOVE 37°C
DO NOT MICROWAVE
DO NOT REFRIGERATE OR RE-FREEZE

Do not use TISSEEL (frozen) until it is completely thawed and warmed (liquid consistency).

Do not remove the protective syringe cap until use.

TISSEEL (frozen) can be prepared (thawed) using one of two options:

Room Temperature Thawing

Unopened pouches may be stored for up to 48 hours at room temperature (15-25°C).

When product is thawed at room temperature, warm to 33-37°C prior to use and use immediately. The total thawing and warming time cannot exceed 48 hours.

Quick Thawing

Option 1 – Thawing on the sterile field using a water bath

33°C to 37°C sterile water bath - transfer DUO set and the inner pouch to the sterile field, remove pre-filled syringe from inner pouch and place directly into sterile water bath. Ensure the contents of the pre-filled syringe are completely immersed under the water.

Approximate thawing and warming times when using this method are:

Pack Size Thawing/Warming Times
33°C to 37°C Sterile Water Bath
(Pouches Removed) 2 mL 5 minutes 4 mL 5 minutes 10 mL 12 minutes

Option 2 – Thawing off the sterile field using a water bath

33°C to 37°C non-sterile water bath in two pouches - maintain the pre-filled syringe in both pouches and place into a water bath off the sterile field for appropriate time. Ensure the pouches remain submerged throughout thawing. Remove from the water bath after thawing, dry external pouch and transfer inner pouch with pre-filled syringe onto the sterile field.

Approximate thawing and warming times when using this method are:

Pack Size Thawing/Warming Times
33°C to 37°C Non-Sterile Water Bath
(In Pouches) 2 mL 30 minutes 4 mL 40 minutes 10 mL 80 minutes

Option 3 – Thawing off the sterile field using an incubator

33°C to 37°C incubator in pouches – maintain the pre-filled syringe in both pouches and place into an incubator for appropriate time. Remove from incubator after thawing and transfer inner pouch with pre-filled syringe onto the sterile field.

Approximate thawing and warming times when using this method are:

Pack Size Thawing/Warming Times
33°C to 37°C Incubator
(In Pouches) 2 mL 40 minutes 4 mL 85 minutes 10 mL 105 minutes

Maintain the product at 33-37°C until use. If the package is opened or warmed to 33-37°C it must be used within 4 hours.

See DOSAGE AND ADMINISTRATION, Method of Application (2.3).

2.3 Method of Application

Vials and pre-filled syringes are for single use only. Discard any unused product.

The wound surface should be as dry as possible before application.

Avoid application beyond the intended area.

Immediately before application, expel and discard the first several drops from the application cannula to ensure adequate mixing of the Sealer Protein and Thrombin solutions in cases where very small volumes (1-2 drops) of product are administered.

To prevent adherence, wet gloves with normal saline before product contact.

Apply TISSEEL as a thin layer. The initial amount of the product to be applied should be sufficient to entirely cover the intended application area. The application can be repeated, if necessary. If repeat application is necessary, reapply before polymerization takes place since TISSEEL may not adhere to a polymerized layer.

After the two components have been applied, fix or hold the sealed parts in the desired position for at least three to five minutes to ensure the setting TISSEEL adheres firmly to the surrounding tissue.

 

TISSEEL Kit (Freeze-Dried)

Apply TISSEEL using the DUPLOJECT Fibrin Sealant Preparation and Application System or an equivalent delivery device cleared by FDA for use with TISSEEL. Specific instructions for the use of TISSEEL in conjunction with each cleared delivery device are provided with the device.

TISSEEL Pre-filled Syringe (Frozen)

Apply pre-filled TISSEEL using the DUO Set accessory devices provided with the product or an equivalent delivery device cleared by FDA for use with TISSEEL.

DUO Set Instructions (see Figure 1 below):

Insert plunger into syringe barrel. Firmly connect the two syringe nozzles to the joining piece and secure it by fastening the tether strap to the syringe. Fit an application cannula to the joining piece. Apply by depressing plunger.

Note: Interruption of TISSEEL application causes clogging in the cannula. Replace the cannula immediately prior to resuming application. If the opening of the joining piece (Y connector) facing the cannula is clogged, use the spare joining piece provided in the package.

Figure 1 DUO SET

FOR TOPICAL USE ONLY – DO NOT INJECT.

The required dose of TISSEEL depends on the size of the surface to be covered. The approximate surface areas covered by each package size of TISSEEL are listed in the following table:

Table 1 Maximum size of the area to be sealed using cannula Maximum size of the area to be sealed using compressed gas Required package size of TISSEEL 8 cm2 100 cm2 2 mL 16 cm2 200 cm2 4 mL 40 cm2 500 cm2 10 mL

It is recommended that every time a patient receives a dose of TISSEEL, the name and batch number of the product are documented in order to maintain a record of the batches used.

2.1 Preparation of TISSEEL Kit (Freeze-Dried)

During preparation of TISSEEL Kit:

DO NOT EXPOSE TO TEMPERATURES ABOVE 37°C

DO NOT MICROWAVE
DO NOT REFRIGERATE OR FREEZE AFTER RECONSTITUTION

Do not use iodine or heavy metal containing preparations such as betadine for disinfection of vial stoppers. Allow alcohol-based disinfectants to evaporate before puncturing stopper.

Use separate syringes for reconstituting Sealer Protein and Thrombin solutions and for application to prevent premature clotting.

After reconstitution, the product must be used within 4 hours.

TISSEEL Kit contains the following substances in four separate vials:

-Sealer Protein Concentrate (Human)

-Fibrinolysis Inhibitor Solution (Synthetic)

-Thrombin (Human)

-Calcium Chloride Solution

Freeze-dried Sealer Protein Concentrate and Thrombin are reconstituted in Fibrinolysis Inhibitor Solution and Calcium Chloride Solution, respectively. The Sealer Protein Solution and Thrombin Solution are then combined using the DUPLOJECT Preparation and Application System, or an equivalent delivery device cleared by FDA for use with TISSEEL, to form the Fibrin Sealant.

Prewarming TISSEEL Kit with FIBRINOTHERM

If a FIBRINOTHERM device is not available, contact Baxter (1-800-423-2090) for assistance. See FIBRINOTHERM manual for complete operating instructions.

Plug the FIBRINOTHERM Heating and Stirring Device into an electrical socket and activate the warmer (amber switch). Ensure that the stirring mechanism of the FIBRINOTHERM device is initially switched off (green switch). Place all four vials from the TISSEEL Kit into the prewarmed wells of the FIBRINOTHERM, using the appropriately sized adapter rings, and allow the vials to warm for up to 5 minutes (room temperature product may take less time).

Preparation of Sealer Protein Solution with FIBRINOTHERM

Remove the flip-off caps from the vial containing the Sealer Protein Concentrate and the vial containing the Fibrinolysis Inhibitor Solution, disinfect the rubber stoppers of both vials with a germicidal solution and allow to dry. Transfer the Fibrinolysis Inhibitor Solution into the vial containing the freeze-dried Sealer Protein Concentrate using the sterile reconstitution components provided with the DUPLOJECT Preparation and Application System, or an equivalent device cleared by FDA for use with TISSEEL (see directions provided with the device system for specific reconstitution instructions). Gently swirl the vial to ensure that the freeze-dried material is completely soaked. Place the vial into the largest opening of the FIBRINOTHERM device with the appropriate adaptor. Switch on the stirrer (green switch) and allow the vial contents to stir until all Sealer Protein Concentrate is dissolved. Reconstitution of the freeze-dried Sealer Protein Concentrate is complete as soon as no undissolved particles are visible. Otherwise, return the vial to the FIBRINOTHERM device and agitate for a few more minutes until the solution appears homogeneous.

Notes:

-Do not use the Sealer Protein Concentrate until it has fully dissolved. If the Sealer Protein Concentrate has not dissolved within 20 minutes using the FIBRINOTHERM device, discard the vial and prepare a fresh kit.

-If not used promptly, keep the Sealer Protein Solution at 37°C without stirring. To ensure homogeneity, switch on the stirrer of the FIBRINOTHERM device shortly before drawing up the solution.

Preparation of Thrombin Solution with FIBRINOTHERM

Remove the flip-off caps from the vial containing Thrombin and the vial containing Calcium Chloride Solution, disinfect the rubber stoppers of both vials with a germicidal solution and allow to dry. Transfer the contents of the vial with Calcium Chloride Solution into the vial containing the freeze-dried Thrombin using the sterile reconstitution components provided with the DUPLOJECT Preparation and Application System, or an equivalent device cleared by FDA for use with TISSEEL (see directions provided with the device system for specific reconstitution instructions). Swirl briefly. Place the vial into the adapted opening of the FIBRINOTHERM device. Reconstitution of Thrombin is complete when all of the Thrombin concentrate is dissolved. Keep the Thrombin Solution at 37°C until used.

Transferring to the Sterile Field

For transfer of the Sealer Protein Solution and the Thrombin Solution to the sterile field, the scrub nurse should withdraw the solutions while the circulating nurse holds the non-sterile vials. The solutions should be withdrawn slowly by firm constant aspiration to reduce the risk of large air bubbles.

See DOSAGE AND ADMINISTRATION, Method of Application (2.3).

2.2 Preparation of TISSEEL Pre-Filled Syringe (Frozen)

During preparation of TISSEEL (frozen):

DO NOT EXPOSE TO TEMPERATURES ABOVE 37°C
DO NOT MICROWAVE
DO NOT REFRIGERATE OR RE-FREEZE

Do not use TISSEEL (frozen) until it is completely thawed and warmed (liquid consistency).

Do not remove the protective syringe cap until use.

TISSEEL (frozen) can be prepared (thawed) using one of two options:

Room Temperature Thawing

Unopened pouches may be stored for up to 48 hours at room temperature (15-25°C).

When product is thawed at room temperature, warm to 33-37°C prior to use and use immediately. The total thawing and warming time cannot exceed 48 hours.

Quick Thawing

Option 1 – Thawing on the sterile field using a water bath

33°C to 37°C sterile water bath - transfer DUO set and the inner pouch to the sterile field, remove pre-filled syringe from inner pouch and place directly into sterile water bath. Ensure the contents of the pre-filled syringe are completely immersed under the water.

Approximate thawing and warming times when using this method are:

Pack Size Thawing/Warming Times
33°C to 37°C Sterile Water Bath
(Pouches Removed) 2 mL 5 minutes 4 mL 5 minutes 10 mL 12 minutes

Option 2 – Thawing off the sterile field using a water bath

33°C to 37°C non-sterile water bath in two pouches - maintain the pre-filled syringe in both pouches and place into a water bath off the sterile field for appropriate time. Ensure the pouches remain submerged throughout thawing. Remove from the water bath after thawing, dry external pouch and transfer inner pouch with pre-filled syringe onto the sterile field.

Approximate thawing and warming times when using this method are:

Pack Size Thawing/Warming Times
33°C to 37°C Non-Sterile Water Bath
(In Pouches) 2 mL 30 minutes 4 mL 40 minutes 10 mL 80 minutes

Option 3 – Thawing off the sterile field using an incubator

33°C to 37°C incubator in pouches – maintain the pre-filled syringe in both pouches and place into an incubator for appropriate time. Remove from incubator after thawing and transfer inner pouch with pre-filled syringe onto the sterile field.

Approximate thawing and warming times when using this method are:

Pack Size Thawing/Warming Times
33°C to 37°C Incubator
(In Pouches) 2 mL 40 minutes 4 mL 85 minutes 10 mL 105 minutes

Maintain the product at 33-37°C until use. If the package is opened or warmed to 33-37°C it must be used within 4 hours.

See DOSAGE AND ADMINISTRATION, Method of Application (2.3).

2.3 Method of Application

Vials and pre-filled syringes are for single use only. Discard any unused product.

The wound surface should be as dry as possible before application.

Avoid application beyond the intended area.

Immediately before application, expel and discard the first several drops from the application cannula to ensure adequate mixing of the Sealer Protein and Thrombin solutions in cases where very small volumes (1-2 drops) of product are administered.

To prevent adherence, wet gloves with normal saline before product contact.

Apply TISSEEL as a thin layer. The initial amount of the product to be applied should be sufficient to entirely cover the intended application area. The application can be repeated, if necessary. If repeat application is necessary, reapply before polymerization takes place since TISSEEL may not adhere to a polymerized layer.

After the two components have been applied, fix or hold the sealed parts in the desired position for at least three to five minutes to ensure the setting TISSEEL adheres firmly to the surrounding tissue.

 

TISSEEL Kit (Freeze-Dried)

Apply TISSEEL using the DUPLOJECT Fibrin Sealant Preparation and Application System or an equivalent delivery device cleared by FDA for use with TISSEEL. Specific instructions for the use of TISSEEL in conjunction with each cleared delivery device are provided with the device.

TISSEEL Pre-filled Syringe (Frozen)

Apply pre-filled TISSEEL using the DUO Set accessory devices provided with the product or an equivalent delivery device cleared by FDA for use with TISSEEL.

DUO Set Instructions (see Figure 1 below):

Insert plunger into syringe barrel. Firmly connect the two syringe nozzles to the joining piece and secure it by fastening the tether strap to the syringe. Fit an application cannula to the joining piece. Apply by depressing plunger.

Note: Interruption of TISSEEL application causes clogging in the cannula. Replace the cannula immediately prior to resuming application. If the opening of the joining piece (Y connector) facing the cannula is clogged, use the spare joining piece provided in the package.

Figure 1 DUO SET

FOR TOPICAL USE ONLY – DO NOT INJECT.

The required dose of TISSEEL depends on the size of the surface to be covered. The approximate surface areas covered by each package size of TISSEEL are listed in the following table:

Table 1 Maximum size of the area to be sealed using cannula Maximum size of the area to be sealed using compressed gas Required package size of TISSEEL 8 cm2 100 cm2 2 mL 16 cm2 200 cm2 4 mL 40 cm2 500 cm2 10 mL

It is recommended that every time a patient receives a dose of TISSEEL, the name and batch number of the product are documented in order to maintain a record of the batches used.

2.1 Preparation of TISSEEL Kit (Freeze-Dried)

During preparation of TISSEEL Kit:

DO NOT EXPOSE TO TEMPERATURES ABOVE 37°C

DO NOT MICROWAVE
DO NOT REFRIGERATE OR FREEZE AFTER RECONSTITUTION

Do not use iodine or heavy metal containing preparations such as betadine for disinfection of vial stoppers. Allow alcohol-based disinfectants to evaporate before puncturing stopper.

Use separate syringes for reconstituting Sealer Protein and Thrombin solutions and for application to prevent premature clotting.

After reconstitution, the product must be used within 4 hours.

TISSEEL Kit contains the following substances in four separate vials:

-Sealer Protein Concentrate (Human)

-Fibrinolysis Inhibitor Solution (Synthetic)

-Thrombin (Human)

-Calcium Chloride Solution

Freeze-dried Sealer Protein Concentrate and Thrombin are reconstituted in Fibrinolysis Inhibitor Solution and Calcium Chloride Solution, respectively. The Sealer Protein Solution and Thrombin Solution are then combined using the DUPLOJECT Preparation and Application System, or an equivalent delivery device cleared by FDA for use with TISSEEL, to form the Fibrin Sealant.

Prewarming TISSEEL Kit with FIBRINOTHERM

If a FIBRINOTHERM device is not available, contact Baxter (1-800-423-2090) for assistance. See FIBRINOTHERM manual for complete operating instructions.

Plug the FIBRINOTHERM Heating and Stirring Device into an electrical socket and activate the warmer (amber switch). Ensure that the stirring mechanism of the FIBRINOTHERM device is initially switched off (green switch). Place all four vials from the TISSEEL Kit into the prewarmed wells of the FIBRINOTHERM, using the appropriately sized adapter rings, and allow the vials to warm for up to 5 minutes (room temperature product may take less time).

Preparation of Sealer Protein Solution with FIBRINOTHERM

Remove the flip-off caps from the vial containing the Sealer Protein Concentrate and the vial containing the Fibrinolysis Inhibitor Solution, disinfect the rubber stoppers of both vials with a germicidal solution and allow to dry. Transfer the Fibrinolysis Inhibitor Solution into the vial containing the freeze-dried Sealer Protein Concentrate using the sterile reconstitution components provided with the DUPLOJECT Preparation and Application System, or an equivalent device cleared by FDA for use with TISSEEL (see directions provided with the device system for specific reconstitution instructions). Gently swirl the vial to ensure that the freeze-dried material is completely soaked. Place the vial into the largest opening of the FIBRINOTHERM device with the appropriate adaptor. Switch on the stirrer (green switch) and allow the vial contents to stir until all Sealer Protein Concentrate is dissolved. Reconstitution of the freeze-dried Sealer Protein Concentrate is complete as soon as no undissolved particles are visible. Otherwise, return the vial to the FIBRINOTHERM device and agitate for a few more minutes until the solution appears homogeneous.

Notes:

-Do not use the Sealer Protein Concentrate until it has fully dissolved. If the Sealer Protein Concentrate has not dissolved within 20 minutes using the FIBRINOTHERM device, discard the vial and prepare a fresh kit.

-If not used promptly, keep the Sealer Protein Solution at 37°C without stirring. To ensure homogeneity, switch on the stirrer of the FIBRINOTHERM device shortly before drawing up the solution.

Preparation of Thrombin Solution with FIBRINOTHERM

Remove the flip-off caps from the vial containing Thrombin and the vial containing Calcium Chloride Solution, disinfect the rubber stoppers of both vials with a germicidal solution and allow to dry. Transfer the contents of the vial with Calcium Chloride Solution into the vial containing the freeze-dried Thrombin using the sterile reconstitution components provided with the DUPLOJECT Preparation and Application System, or an equivalent device cleared by FDA for use with TISSEEL (see directions provided with the device system for specific reconstitution instructions). Swirl briefly. Place the vial into the adapted opening of the FIBRINOTHERM device. Reconstitution of Thrombin is complete when all of the Thrombin concentrate is dissolved. Keep the Thrombin Solution at 37°C until used.

Transferring to the Sterile Field

For transfer of the Sealer Protein Solution and the Thrombin Solution to the sterile field, the scrub nurse should withdraw the solutions while the circulating nurse holds the non-sterile vials. The solutions should be withdrawn slowly by firm constant aspiration to reduce the risk of large air bubbles.

See DOSAGE AND ADMINISTRATION, Method of Application (2.3).

2.2 Preparation of TISSEEL Pre-Filled Syringe (Frozen)

During preparation of TISSEEL (frozen):

DO NOT EXPOSE TO TEMPERATURES ABOVE 37°C
DO NOT MICROWAVE
DO NOT REFRIGERATE OR RE-FREEZE

Do not use TISSEEL (frozen) until it is completely thawed and warmed (liquid consistency).

Do not remove the protective syringe cap until use.

TISSEEL (frozen) can be prepared (thawed) using one of two options:

Room Temperature Thawing

Unopened pouches may be stored for up to 48 hours at room temperature (15-25°C).

When product is thawed at room temperature, warm to 33-37°C prior to use and use immediately. The total thawing and warming time cannot exceed 48 hours.

Quick Thawing

Option 1 – Thawing on the sterile field using a water bath

33°C to 37°C sterile water bath - transfer DUO set and the inner pouch to the sterile field, remove pre-filled syringe from inner pouch and place directly into sterile water bath. Ensure the contents of the pre-filled syringe are completely immersed under the water.

Approximate thawing and warming times when using this method are:

Pack Size Thawing/Warming Times
33°C to 37°C Sterile Water Bath
(Pouches Removed) 2 mL 5 minutes 4 mL 5 minutes 10 mL 12 minutes

Option 2 – Thawing off the sterile field using a water bath

33°C to 37°C non-sterile water bath in two pouches - maintain the pre-filled syringe in both pouches and place into a water bath off the sterile field for appropriate time. Ensure the pouches remain submerged throughout thawing. Remove from the water bath after thawing, dry external pouch and transfer inner pouch with pre-filled syringe onto the sterile field.

Approximate thawing and warming times when using this method are:

Pack Size Thawing/Warming Times
33°C to 37°C Non-Sterile Water Bath
(In Pouches) 2 mL 30 minutes 4 mL 40 minutes 10 mL 80 minutes

Option 3 – Thawing off the sterile field using an incubator

33°C to 37°C incubator in pouches – maintain the pre-filled syringe in both pouches and place into an incubator for appropriate time. Remove from incubator after thawing and transfer inner pouch with pre-filled syringe onto the sterile field.

Approximate thawing and warming times when using this method are:

Pack Size Thawing/Warming Times
33°C to 37°C Incubator
(In Pouches) 2 mL 40 minutes 4 mL 85 minutes 10 mL 105 minutes

Maintain the product at 33-37°C until use. If the package is opened or warmed to 33-37°C it must be used within 4 hours.

See DOSAGE AND ADMINISTRATION, Method of Application (2.3).

2.3 Method of Application

Vials and pre-filled syringes are for single use only. Discard any unused product.

The wound surface should be as dry as possible before application.

Avoid application beyond the intended area.

Immediately before application, expel and discard the first several drops from the application cannula to ensure adequate mixing of the Sealer Protein and Thrombin solutions in cases where very small volumes (1-2 drops) of product are administered.

To prevent adherence, wet gloves with normal saline before product contact.

Apply TISSEEL as a thin layer. The initial amount of the product to be applied should be sufficient to entirely cover the intended application area. The application can be repeated, if necessary. If repeat application is necessary, reapply before polymerization takes place since TISSEEL may not adhere to a polymerized layer.

After the two components have been applied, fix or hold the sealed parts in the desired position for at least three to five minutes to ensure the setting TISSEEL adheres firmly to the surrounding tissue.

 

TISSEEL Kit (Freeze-Dried)

Apply TISSEEL using the DUPLOJECT Fibrin Sealant Preparation and Application System or an equivalent delivery device cleared by FDA for use with TISSEEL. Specific instructions for the use of TISSEEL in conjunction with each cleared delivery device are provided with the device.

TISSEEL Pre-filled Syringe (Frozen)

Apply pre-filled TISSEEL using the DUO Set accessory devices provided with the product or an equivalent delivery device cleared by FDA for use with TISSEEL.

DUO Set Instructions (see Figure 1 below):

Insert plunger into syringe barrel. Firmly connect the two syringe nozzles to the joining piece and secure it by fastening the tether strap to the syringe. Fit an application cannula to the joining piece. Apply by depressing plunger.

Note: Interruption of TISSEEL application causes clogging in the cannula. Replace the cannula immediately prior to resuming application. If the opening of the joining piece (Y connector) facing the cannula is clogged, use the spare joining piece provided in the package.

Figure 1 DUO SET

FOR TOPICAL USE ONLY – DO NOT INJECT.

The required dose of TISSEEL depends on the size of the surface to be covered. The approximate surface areas covered by each package size of TISSEEL are listed in the following table:

Table 1 Maximum size of the area to be sealed using cannula Maximum size of the area to be sealed using compressed gas Required package size of TISSEEL 8 cm2 100 cm2 2 mL 16 cm2 200 cm2 4 mL 40 cm2 500 cm2 10 mL

It is recommended that every time a patient receives a dose of TISSEEL, the name and batch number of the product are documented in order to maintain a record of the batches used.

2.1 Preparation of TISSEEL Kit (Freeze-Dried)

During preparation of TISSEEL Kit:

DO NOT EXPOSE TO TEMPERATURES ABOVE 37°C

DO NOT MICROWAVE
DO NOT REFRIGERATE OR FREEZE AFTER RECONSTITUTION

Do not use iodine or heavy metal containing preparations such as betadine for disinfection of vial stoppers. Allow alcohol-based disinfectants to evaporate before puncturing stopper.

Use separate syringes for reconstituting Sealer Protein and Thrombin solutions and for application to prevent premature clotting.

After reconstitution, the product must be used within 4 hours.

TISSEEL Kit contains the following substances in four separate vials:

-Sealer Protein Concentrate (Human)

-Fibrinolysis Inhibitor Solution (Synthetic)

-Thrombin (Human)

-Calcium Chloride Solution

Freeze-dried Sealer Protein Concentrate and Thrombin are reconstituted in Fibrinolysis Inhibitor Solution and Calcium Chloride Solution, respectively. The Sealer Protein Solution and Thrombin Solution are then combined using the DUPLOJECT Preparation and Application System, or an equivalent delivery device cleared by FDA for use with TISSEEL, to form the Fibrin Sealant.

Prewarming TISSEEL Kit with FIBRINOTHERM

If a FIBRINOTHERM device is not available, contact Baxter (1-800-423-2090) for assistance. See FIBRINOTHERM manual for complete operating instructions.

Plug the FIBRINOTHERM Heating and Stirring Device into an electrical socket and activate the warmer (amber switch). Ensure that the stirring mechanism of the FIBRINOTHERM device is initially switched off (green switch). Place all four vials from the TISSEEL Kit into the prewarmed wells of the FIBRINOTHERM, using the appropriately sized adapter rings, and allow the vials to warm for up to 5 minutes (room temperature product may take less time).

Preparation of Sealer Protein Solution with FIBRINOTHERM

Remove the flip-off caps from the vial containing the Sealer Protein Concentrate and the vial containing the Fibrinolysis Inhibitor Solution, disinfect the rubber stoppers of both vials with a germicidal solution and allow to dry. Transfer the Fibrinolysis Inhibitor Solution into the vial containing the freeze-dried Sealer Protein Concentrate using the sterile reconstitution components provided with the DUPLOJECT Preparation and Application System, or an equivalent device cleared by FDA for use with TISSEEL (see directions provided with the device system for specific reconstitution instructions). Gently swirl the vial to ensure that the freeze-dried material is completely soaked. Place the vial into the largest opening of the FIBRINOTHERM device with the appropriate adaptor. Switch on the stirrer (green switch) and allow the vial contents to stir until all Sealer Protein Concentrate is dissolved. Reconstitution of the freeze-dried Sealer Protein Concentrate is complete as soon as no undissolved particles are visible. Otherwise, return the vial to the FIBRINOTHERM device and agitate for a few more minutes until the solution appears homogeneous.

Notes:

-Do not use the Sealer Protein Concentrate until it has fully dissolved. If the Sealer Protein Concentrate has not dissolved within 20 minutes using the FIBRINOTHERM device, discard the vial and prepare a fresh kit.

-If not used promptly, keep the Sealer Protein Solution at 37°C without stirring. To ensure homogeneity, switch on the stirrer of the FIBRINOTHERM device shortly before drawing up the solution.

Preparation of Thrombin Solution with FIBRINOTHERM

Remove the flip-off caps from the vial containing Thrombin and the vial containing Calcium Chloride Solution, disinfect the rubber stoppers of both vials with a germicidal solution and allow to dry. Transfer the contents of the vial with Calcium Chloride Solution into the vial containing the freeze-dried Thrombin using the sterile reconstitution components provided with the DUPLOJECT Preparation and Application System, or an equivalent device cleared by FDA for use with TISSEEL (see directions provided with the device system for specific reconstitution instructions). Swirl briefly. Place the vial into the adapted opening of the FIBRINOTHERM device. Reconstitution of Thrombin is complete when all of the Thrombin concentrate is dissolved. Keep the Thrombin Solution at 37°C until used.

Transferring to the Sterile Field

For transfer of the Sealer Protein Solution and the Thrombin Solution to the sterile field, the scrub nurse should withdraw the solutions while the circulating nurse holds the non-sterile vials. The solutions should be withdrawn slowly by firm constant aspiration to reduce the risk of large air bubbles.

See DOSAGE AND ADMINISTRATION, Method of Application (2.3).

2.2 Preparation of TISSEEL Pre-Filled Syringe (Frozen)

During preparation of TISSEEL (frozen):

DO NOT EXPOSE TO TEMPERATURES ABOVE 37°C
DO NOT MICROWAVE
DO NOT REFRIGERATE OR RE-FREEZE

Do not use TISSEEL (frozen) until it is completely thawed and warmed (liquid consistency).

Do not remove the protective syringe cap until use.

TISSEEL (frozen) can be prepared (thawed) using one of two options:

Room Temperature Thawing

Unopened pouches may be stored for up to 48 hours at room temperature (15-25°C).

When product is thawed at room temperature, warm to 33-37°C prior to use and use immediately. The total thawing and warming time cannot exceed 48 hours.

Quick Thawing

Option 1 – Thawing on the sterile field using a water bath

33°C to 37°C sterile water bath - transfer DUO set and the inner pouch to the sterile field, remove pre-filled syringe from inner pouch and place directly into sterile water bath. Ensure the contents of the pre-filled syringe are completely immersed under the water.

Approximate thawing and warming times when using this method are:

Pack Size Thawing/Warming Times
33°C to 37°C Sterile Water Bath
(Pouches Removed) 2 mL 5 minutes 4 mL 5 minutes 10 mL 12 minutes

Option 2 – Thawing off the sterile field using a water bath

33°C to 37°C non-sterile water bath in two pouches - maintain the pre-filled syringe in both pouches and place into a water bath off the sterile field for appropriate time. Ensure the pouches remain submerged throughout thawing. Remove from the water bath after thawing, dry external pouch and transfer inner pouch with pre-filled syringe onto the sterile field.

Approximate thawing and warming times when using this method are:

Pack Size Thawing/Warming Times
33°C to 37°C Non-Sterile Water Bath
(In Pouches) 2 mL 30 minutes 4 mL 40 minutes 10 mL 80 minutes

Option 3 – Thawing off the sterile field using an incubator

33°C to 37°C incubator in pouches – maintain the pre-filled syringe in both pouches and place into an incubator for appropriate time. Remove from incubator after thawing and transfer inner pouch with pre-filled syringe onto the sterile field.

Approximate thawing and warming times when using this method are:

Pack Size Thawing/Warming Times
33°C to 37°C Incubator
(In Pouches) 2 mL 40 minutes 4 mL 85 minutes 10 mL 105 minutes

Maintain the product at 33-37°C until use. If the package is opened or warmed to 33-37°C it must be used within 4 hours.

See DOSAGE AND ADMINISTRATION, Method of Application (2.3).

2.3 Method of Application

Vials and pre-filled syringes are for single use only. Discard any unused product.

The wound surface should be as dry as possible before application.

Avoid application beyond the intended area.

Immediately before application, expel and discard the first several drops from the application cannula to ensure adequate mixing of the Sealer Protein and Thrombin solutions in cases where very small volumes (1-2 drops) of product are administered.

To prevent adherence, wet gloves with normal saline before product contact.

Apply TISSEEL as a thin layer. The initial amount of the product to be applied should be sufficient to entirely cover the intended application area. The application can be repeated, if necessary. If repeat application is necessary, reapply before polymerization takes place since TISSEEL may not adhere to a polymerized layer.

After the two components have been applied, fix or hold the sealed parts in the desired position for at least three to five minutes to ensure the setting TISSEEL adheres firmly to the surrounding tissue.

 

TISSEEL Kit (Freeze-Dried)

Apply TISSEEL using the DUPLOJECT Fibrin Sealant Preparation and Application System or an equivalent delivery device cleared by FDA for use with TISSEEL. Specific instructions for the use of TISSEEL in conjunction with each cleared delivery device are provided with the device.

TISSEEL Pre-filled Syringe (Frozen)

Apply pre-filled TISSEEL using the DUO Set accessory devices provided with the product or an equivalent delivery device cleared by FDA for use with TISSEEL.

DUO Set Instructions (see Figure 1 below):

Insert plunger into syringe barrel. Firmly connect the two syringe nozzles to the joining piece and secure it by fastening the tether strap to the syringe. Fit an application cannula to the joining piece. Apply by depressing plunger.

Note: Interruption of TISSEEL application causes clogging in the cannula. Replace the cannula immediately prior to resuming application. If the opening of the joining piece (Y connector) facing the cannula is clogged, use the spare joining piece provided in the package.

Figure 1 DUO SET

FOR TOPICAL USE ONLY – DO NOT INJECT

Vials and pre-filled syringes are for single use only. Discard any unused product.

2.1 Preparation of TISSEEL Kit (Freeze-Dried)

 

DO NOT EXPOSE TO TEMPERATURES ABOVE 37°C

DO NOT MICROWAVE
DO NOT REFRIGERATE OR FREEZE AFTER RECONSTITUTION

Do not use iodine or heavy metal containing preparations such as betadine for disinfection of vial stoppers.

Allow alcohol-based disinfectants to evaporate before puncturing stopper.

Use separate syringes and transfer devices for reconstituting Sealer Protein and Thrombin solutions and for application to prevent clotting.

The product must be used within 4 hours after reconstitution.

Freeze-dried Sealer Protein Concentrate and Thrombin are reconstituted in Fibrinolysis Inhibitor Solution and Calcium Chloride Solution, respectively. The Sealer Protein Solution and Thrombin Solution are then combined using the DUPLOJECT Preparation and Application System, or an equivalent delivery device cleared by FDA for use with TISSEEL, to form the Fibrin Sealant.

Prewarming TISSEEL Kit with FIBRINOTHERM

See FIBRINOTHERM manual for complete operating instructions. If a FIBRINOTHERM device is not available, contact Baxter (1-800-423-2090) for assistance.

Place all four vials from the TISSEEL Kit into the prewarmed wells of the FIBRINOTHERM, using the appropriately sized adapter ring(s), and allow the vials to warm for up to 5 minutes (room temperature product will take less time).

Preparation of Sealer Protein Solution with FIBRINOTHERM

Remove the caps from the Sealer Protein Concentrate and the Fibrinolysis Inhibitor Solution vials. Transfer the Fibrinolysis Inhibitor Solution into the vial containing the freeze-dried Sealer Protein Concentrate using the sterile reconstitution components (see directions provided with the device system for specific reconstitution instructions). Gently swirl the vial to ensure that the product is completely soaked. Place the vial into the largest opening of the FIBRINOTHERM device with the appropriate adaptor. Switch on the stirrer and allow the vial contents to stir until all Sealer Protein Concentrate is dissolved. Reconstitution is complete when no undissolved particles are visible.

Notes:

-If the Sealer Protein Concentrate has not fully dissolved within 20 minutes discard the vial and prepare a fresh kit.

-Keep the Sealer Protein Solution at 37°C without stirring. Stir shortly before drawing up the solution to ensure homogeneity.

Preparation of Thrombin Solution with FIBRINOTHERM

To reconstitute the Thrombin (Human) with the Calcium Chloride Solution; follow steps 1-3 under Preparation of Sealer Protein with FIBRINOTHERM utilizing the Thrombin and Calcium Chloride vials.

Transferring to the Sterile Field

For transfer of the Sealer Protein and Thrombin Solutions to the sterile field, the circulating nurse should disinfect the tops of the vials with a germicidal solution and allow to dry. The scrub nurse should withdraw the sterile solutions while the circulating nurse holds the non-sterile vials. Slowly withdraw the solution, by firm constant aspiration, to reduce the risk of large air bubbles.

2.2 Preparation of TISSEEL Pre-Filled Syringe (Frozen)

DO NOT EXPOSE TO TEMPERATURES ABOVE 37°C

DO NOT MICROWAVE
DO NOT REFRIGERATE OR RE-FREEZE
 

Do not use TISSEEL (frozen) until it is completely thawed and warmed (liquid consistency) to 33-37ºC.

Do not remove the protective syringe cap until use.

 Sterile Water Bath (Quick Thawing): Transfer inner pouch to the sterile field, remove pre-filled syringe from inner pouch and place directly into sterile water bath ensuring the syringe is completely immersed in the water. Maintain the product at 33-37°C until use. If the package is opened or warmed to 33-37°C, it must be used within 4 hours.

Non-Sterile Water Bath: Maintain the pre-filled syringe in pouches and place into a water bath outside the sterile field ensuring the pouches remain submerged. Remove from the water bath after thawing and warming, dry the external pouch and transfer inner pouch with pre-filled syringe onto the sterile field. Maintain the product at 33-37°C until use. If the package is opened or warmed to 33-37°C, it must be used within 4 hours.

Incubator: Maintain the pre-filled syringe in pouches and place into an incubator. Remove from the incubator after thawing and warming. Transfer inner pouch with pre-filled syringe onto the sterile field. Maintain the product at 33-37°C until use. If the package is opened or warmed to 33-37°C, it must be used within 4 hours.

Table 1: Approximate Water Bath or Incubator Thawing and Warming Times Pack Size

Sterile Water Bath
(Pouches Removed)

33 - 37°C

Non-Sterile Water Bath

(In Pouches)

33 - 37°C

Incubator

(In Pouches)

33 - 37°C 2 mL 5 minutes 30 minutes 40 minutes 4 mL 5 minutes 40 minutes 85 minutes 10 mL 12 minutes 80 minutes 105 minutes

Room Temperature Thawing: Unopened pouches can be stored for up to 48 hours at room temperature (15-25°C). Before use, warm the product to 33-37ºC and apply immediately. The total thawing and warming time cannot exceed 48 hours.

 

Table 2: Approximate Room Temperature Thawing Times Pack Size

Room Temperature

(In Pouches)

15 – 25oC 2 mL 60 minutes 4 mL 110 minutes 10 mL 160 minutes

 

Table 3: Approximate Water Bath or Incubator Warming Times for Thawed Product Pack Size

Sterile Water Bath
(Pouches Removed)

33 – 37°C

Non-Sterile Water Bath

(In Pouches)

33 – 37°C

Incubator

(In Pouches)

33 – 37°C 2 mL 2 minutes 16 minutes 20 minutes 4 mL 2 minutes 21 minutes 43 minutes 10 mL 6 minutes 43 minutes 52 minutes 2.3 Method of Application

Dry the site of application as much as possible.

Apply TISSEEL as a thin layer by dripping or spraying using a cannula or spray set. The treating physician will determine the amount of TISSEEL to be applied based on the surface to be covered. Ensure that the amount applied is sufficient to entirely cover the intended application area. The approximate surface areas covered by each package size of TISSEEL are listed in Table 4:

Table 4: Surface Area Coverage

Required package size of

TISSEEL Maximum coverage using spray Maximum coverage using cannula

2 mL

4 mL

10 mL

100 cm2

200 cm2

500 cm2

8 cm2

16 cm2

40 cm2

 Avoid application beyond the intended area. Allow at least 2 minutes after application to achieve sufficient polymerization. If repeat application is needed, dry the site as much as possible before reapplying. Reapply after removing residues from the prior application or before polymerization takes place since TISSEEL may not adhere firmly to a polymerized layer.

In cases where very small volumes (1-2 drops) are required, expel and discard the first several drops from the application cannula immediately before application to ensure administration of adequately mixed TISSEEL.

Exercise caution when applying TISSEEL using pressurized gas (see Warnings and Precautions (5.2)).

Record the product name, batch number and patient information for traceability purposes.

TISSEEL Kit (Freeze-Dried)

Apply TISSEEL using the DUPLOJECT Fibrin Sealant Preparation and Application System or an equivalent delivery device (including open and minimally invasive spray devices) cleared by FDA for use with TISSEEL. Specific instructions for the use of TISSEEL in conjunction with each cleared delivery device are provided with the device.

TISSEEL Pre-filled Syringe (Frozen)

Apply pre-filled TISSEEL using the DUO Set accessory devices provided with the product or an equivalent delivery device (including open and minimally invasive spray devices) cleared by FDA for use with TISSEEL.

DUO Set Instructions (see Figure 1 below):

Insert plunger into syringe barrel. Firmly connect the two syringe nozzles to the joining piece (Y connector) and secure it by fastening the tether strap to the syringe. Fit an application cannula to the joining piece. Apply by depressing plunger.

Note: Interruption of TISSEEL application causes clogging in the cannula. Replace the cannula immediately prior to resuming application. If the opening of the joining piece (Y connector) facing the cannula is clogged, use the spare joining piece provided in the package.

Figure 1 DUO SET

FOR TOPICAL USE ONLY – DO NOT INJECT

Vials and pre-filled syringes are for single use only. Discard any unused product.

2.1 Preparation of TISSEEL Kit (Freeze-Dried)

 

DO NOT EXPOSE TO TEMPERATURES ABOVE 37°C

DO NOT MICROWAVE
DO NOT REFRIGERATE OR FREEZE AFTER RECONSTITUTION

Do not use iodine or heavy metal containing preparations such as betadine for disinfection of vial stoppers.

Allow alcohol-based disinfectants to evaporate before puncturing stopper.

Use separate syringes and transfer devices for reconstituting Sealer Protein and Thrombin solutions and for application to prevent clotting.

The product must be used within 4 hours after reconstitution.

Freeze-dried Sealer Protein Concentrate and Thrombin are reconstituted in Fibrinolysis Inhibitor Solution and Calcium Chloride Solution, respectively. The Sealer Protein Solution and Thrombin Solution are then combined using the DUPLOJECT Preparation and Application System, or an equivalent delivery device cleared by FDA for use with TISSEEL, to form the Fibrin Sealant.

Prewarming TISSEEL Kit with FIBRINOTHERM

See FIBRINOTHERM manual for complete operating instructions. If a FIBRINOTHERM device is not available, contact Baxter (1-800-423-2090) for assistance.

Place all four vials from the TISSEEL Kit into the prewarmed wells of the FIBRINOTHERM, using the appropriately sized adapter ring(s), and allow the vials to warm for up to 5 minutes (room temperature product will take less time).

Preparation of Sealer Protein Solution with FIBRINOTHERM

Remove the caps from the Sealer Protein Concentrate and the Fibrinolysis Inhibitor Solution vials. Transfer the Fibrinolysis Inhibitor Solution into the vial containing the freeze-dried Sealer Protein Concentrate using the sterile reconstitution components (see directions provided with the device system for specific reconstitution instructions). Gently swirl the vial to ensure that the product is completely soaked. Place the vial into the largest opening of the FIBRINOTHERM device with the appropriate adaptor. Switch on the stirrer and allow the vial contents to stir until all Sealer Protein Concentrate is dissolved. Reconstitution is complete when no undissolved particles are visible.

Notes:

-If the Sealer Protein Concentrate has not fully dissolved within 20 minutes discard the vial and prepare a fresh kit.

-Keep the Sealer Protein Solution at 37°C without stirring. Stir shortly before drawing up the solution to ensure homogeneity.

Preparation of Thrombin Solution with FIBRINOTHERM

To reconstitute the Thrombin (Human) with the Calcium Chloride Solution; follow steps 1-3 under Preparation of Sealer Protein with FIBRINOTHERM utilizing the Thrombin and Calcium Chloride vials.

Transferring to the Sterile Field

For transfer of the Sealer Protein and Thrombin Solutions to the sterile field, the circulating nurse should disinfect the tops of the vials with a germicidal solution and allow to dry. The scrub nurse should withdraw the sterile solutions while the circulating nurse holds the non-sterile vials. Slowly withdraw the solution, by firm constant aspiration, to reduce the risk of large air bubbles.

2.2 Preparation of TISSEEL Pre-Filled Syringe (Frozen)

DO NOT EXPOSE TO TEMPERATURES ABOVE 37°C

DO NOT MICROWAVE
DO NOT REFRIGERATE OR RE-FREEZE
 

Do not use TISSEEL (frozen) until it is completely thawed and warmed (liquid consistency) to 33-37ºC.

Do not remove the protective syringe cap until use.

 Sterile Water Bath (Quick Thawing): Transfer inner pouch to the sterile field, remove pre-filled syringe from inner pouch and place directly into sterile water bath ensuring the syringe is completely immersed in the water. Maintain the product at 33-37°C until use. If the package is opened or warmed to 33-37°C, it must be used within 4 hours.

Non-Sterile Water Bath: Maintain the pre-filled syringe in pouches and place into a water bath outside the sterile field ensuring the pouches remain submerged. Remove from the water bath after thawing and warming, dry the external pouch and transfer inner pouch with pre-filled syringe onto the sterile field. Maintain the product at 33-37°C until use. If the package is opened or warmed to 33-37°C, it must be used within 4 hours.

Incubator: Maintain the pre-filled syringe in pouches and place into an incubator. Remove from the incubator after thawing and warming. Transfer inner pouch with pre-filled syringe onto the sterile field. Maintain the product at 33-37°C until use. If the package is opened or warmed to 33-37°C, it must be used within 4 hours.

Table 1: Approximate Water Bath or Incubator Thawing and Warming Times Pack Size

Sterile Water Bath
(Pouches Removed)

33 - 37°C

Non-Sterile Water Bath

(In Pouches)

33 - 37°C

Incubator

(In Pouches)

33 - 37°C 2 mL 5 minutes 30 minutes 40 minutes 4 mL 5 minutes 40 minutes 85 minutes 10 mL 12 minutes 80 minutes 105 minutes

Room Temperature Thawing: Unopened pouches can be stored for up to 48 hours at room temperature (15-25°C). Before use, warm the product to 33-37ºC and apply immediately. The total thawing and warming time cannot exceed 48 hours.

 

Table 2: Approximate Room Temperature Thawing Times Pack Size

Room Temperature

(In Pouches)

15 – 25oC 2 mL 60 minutes 4 mL 110 minutes 10 mL 160 minutes

 

Table 3: Approximate Water Bath or Incubator Warming Times for Thawed Product Pack Size

Sterile Water Bath
(Pouches Removed)

33 – 37°C

Non-Sterile Water Bath

(In Pouches)

33 – 37°C

Incubator

(In Pouches)

33 – 37°C 2 mL 2 minutes 16 minutes 20 minutes 4 mL 2 minutes 21 minutes 43 minutes 10 mL 6 minutes 43 minutes 52 minutes 2.3 Method of Application

Dry the site of application as much as possible.

Apply TISSEEL as a thin layer by dripping or spraying using a cannula or spray set. The treating physician will determine the amount of TISSEEL to be applied based on the surface to be covered. Ensure that the amount applied is sufficient to entirely cover the intended application area. The approximate surface areas covered by each package size of TISSEEL are listed in Table 4:

Table 4: Surface Area Coverage

Required package size of

TISSEEL Maximum coverage using spray Maximum coverage using cannula

2 mL

4 mL

10 mL

100 cm2

200 cm2

500 cm2

8 cm2

16 cm2

40 cm2

 Avoid application beyond the intended area. Allow at least 2 minutes after application to achieve sufficient polymerization. If repeat application is needed, dry the site as much as possible before reapplying. Reapply after removing residues from the prior application or before polymerization takes place since TISSEEL may not adhere firmly to a polymerized layer.

In cases where very small volumes (1-2 drops) are required, expel and discard the first several drops from the application cannula immediately before application to ensure administration of adequately mixed TISSEEL.

Exercise caution when applying TISSEEL using pressurized gas (see Warnings and Precautions (5.2)).

Record the product name, batch number and patient information for traceability purposes.

TISSEEL Kit (Freeze-Dried)

Apply TISSEEL using the DUPLOJECT Fibrin Sealant Preparation and Application System or an equivalent delivery device (including open and minimally invasive spray devices) cleared by FDA for use with TISSEEL. Specific instructions for the use of TISSEEL in conjunction with each cleared delivery device are provided with the device.

TISSEEL Pre-filled Syringe (Frozen)

Apply pre-filled TISSEEL using the DUO Set accessory devices provided with the product or an equivalent delivery device (including open and minimally invasive spray devices) cleared by FDA for use with TISSEEL.

DUO Set Instructions (see Figure 1 below):

Insert plunger into syringe barrel. Firmly connect the two syringe nozzles to the joining piece (Y connector) and secure it by fastening the tether strap to the syringe. Fit an application cannula to the joining piece. Apply by depressing plunger.

Note: Interruption of TISSEEL application causes clogging in the cannula. Replace the cannula immediately prior to resuming application. If the opening of the joining piece (Y connector) facing the cannula is clogged, use the spare joining piece provided in the package.

Figure 1 DUO SET