Tisseel

Leaflet accompanying the packaging: information for the user

TISSEEL - Solutions for tissue glue

Human fibrinogen, human thrombin, synthetic aprotinin, calcium chloride dihydrate

Read the leaflet carefully before using the medicine, as it contains important information for the patient.

• Keep this leaflet, you may need to read it again.
• In case of any doubts, consult a doctor or pharmacist.
• If the patient experiences any side effects, including any side effects not listed in this leaflet, tell your doctor, pharmacist, or nurse. See section 4.

Table of contents of the leaflet:

• 1. What is TISSEEL and what is it used for
• 2. Important information before using TISSEEL
• 3. How to use TISSEEL
• 4. Possible side effects
• 5. How to store TISSEEL
• 6. Package contents and other information

1. What is TISSEEL and what is it used for

What is TISSEEL

TISSEEL is a two-component tissue glue consisting of two solutions, a protein glue solution and a thrombin solution. The Tisseel solution contains fibrinogen and thrombin. These are two blood proteins essential for blood clotting. When these proteins are mixed during administration, they form a clot at the site where the surgeon applies them.

The clot formed by TISSEEL is very similar to the natural blood clot. It dissolves in the same way as the endogenous clot (formed naturally in the body) and leaves no residue. The addition of synthetic protein (synthetic aprotinin) is intended to increase the durability of the clot and prevent its premature dissolution.

What is TISSEEL used for

TISSEEL is used as an adjunctive treatment when standard surgical techniques are not sufficient:

to improve hemostasis;

as a tissue glue, facilitating wound healing or as a sealing material for sutures in vascular and gastrointestinal surgery;

to glue tissues, e.g., to secure skin transplants.

TISSEEL is also effective in patients receiving heparin-containing medications that inhibit clotting.

2. Important information before using TISSEEL

When not to use TISSEEL:

• In case of allergy (hypersensitivity) to any of the active substances or any of the other components of this medicine.
• For the treatment of massive arterial or venous bleeding. The use of TISSEEL alone is not indicated in such a situation.
• TISSEEL must not be injected into blood vessels (veins or arteries). Because TISSEEL forms clots at the site of administration, injecting TISSEEL may cause a clot to form in the vessel. If such a clot is carried by the blood, it can lead to life-threatening complications.
• TISSEEL is not intended to replace skin sutures used to close surgical wounds.

Warnings and precautions

Before starting treatment with TISSEEL, discuss it with your doctor, pharmacist, or nurse.

Particular caution should be exercised when using TISSEEL due to the possibility of allergic hypersensitivity reactions.

The first signs of an allergic reaction may include:

• transient skin redness
• itching
• rash
• nausea, vomiting
• general malaise
• chills
• chest tightness
• swelling of the lips and tongue
• breathing difficulties/apnea
• drop in blood pressure
• increase or decrease in heart rate

If any of these symptoms occur, the application should be stopped immediately. In case of severe symptoms, immediate treatment should be initiated as in emergency cases.

Because TISSEEL contains synthetic protein called aprotinin. Even if this protein is administered only in small amounts and only to the surface of the wound, there is a risk of a severe anaphylactic reaction. This risk appears to be higher in patients who have previously used TISSEEL or aprotinin, even if it was previously well tolerated. Therefore, information about the use of aprotinin or products containing aprotinin should be noted in the patient's medical history. Because synthetic aprotinin is structurally identical to bovine aprotinin, the use of TISSEEL should be carefully considered in patients with an allergy to bovine proteins.

Because accidental administration into a blood vessel can lead to life-threatening complications due to the entry of the formed clot into the bloodstream.

Vascular administration, especially in sensitive patients, may increase the likelihood and severity of acute hypersensitivity reactions.

During cardiothoracic surgery, the doctor must exercise particular caution to avoid injecting TISSEEL into a blood vessel. It is also important to avoid injecting into the nasal mucosa due to the risk of blood clots in the arteries of the eye area.

• Because there is a risk of local tissue damage in case of injection of TISSEEL into the tissue.
• To avoid gluing tissues in an undesirable location. Therefore, before use, attention should be paid to whether the areas of the body outside the target application site are sufficiently protected.
• Because too great a thickness of the formed clot may adversely affect the effectiveness of the product and the wound healing process. Therefore, TISSEEL should only be applied in a thin layer.

Care should be taken when applying the fibrin glue using compressed gas.

During the use of spray devices equipped with a pressure regulator for applying fibrin glues to tissues, very rare cases of life-threatening or fatal air and gas embolism have been reported

(involving the entry of air into the bloodstream, which can lead to serious health risks or life-threatening complications). It appears to be related to the use of the spray device at pressure settings higher than recommended and (or) very close to the tissue surface. The risk appears to be higher when fibrin glues are sprayed with air than when they are sprayed with CO2. For this reason, it cannot be ruled out that such an event may occur as a result of spraying the TISSEEL product on open surgical wounds.

The spray device and additional nozzle come with instructions for use, including the manufacturer's recommendations for pressure ranges and distance from the tissue surface during spraying.

The TISSEEL product should be administered strictly according to the instructions and only using devices recommended for use with this product.

During spraying of the TISSEEL product, monitor changes in blood pressure, heart rate, arterial oxygen saturation, and end-tidal CO2 concentration due to the possibility of air or gas embolism (see section 2).

In the manufacture of medicines from human blood or plasma, certain measures are taken to prevent the transmission of infections to patients. These include:

• careful selection of blood and plasma donors to ensure that risk groups for infection are excluded
• testing of individual blood donations and plasma pools for viruses or infections
• incorporation of steps in the blood or plasma processing process that can inactivate or remove viruses

Despite these measures, when medicines made from human blood or plasma are administered, the possibility of transmitting an infection cannot be completely ruled out. This also applies to unknown or newly discovered viruses and other pathogens.

The measures taken are considered effective against enveloped viruses, such as human immunodeficiency virus (HIV), hepatitis B virus, and hepatitis C virus, as well as non-enveloped hepatitis A virus. The measures taken may have limited value against certain non-enveloped viruses, such as parvovirus B19.

Parvovirus B19 infection can be dangerous for pregnant women (fetal infection) and for people with weakened immune systems or certain types of anemia (e.g., congenital spherocytosis or hemolytic anemia).

The attending physician may recommend that the patient consider vaccination against viral hepatitis A and B if the patient is to receive fibrin glue again.

It is strongly recommended that each administration of TISSEEL be documented with the name and batch number of the medicine using the attached self-adhesive label, which should be placed in the patient's medical history.

TISSEEL and other medicines

Tell your doctor or pharmacist about all medicines you are currently taking or have recently taken, as well as any medicines you plan to take, even those available without a prescription.

No interactions between TISSEEL and other medicinal products are known.

Like other comparable preparations or thrombin solutions, the product may denature under the influence of solutions containing alcohol, iodine, or heavy metals (e.g., disinfectant solutions). Before applying the product, the surface should be cleaned as thoroughly as possible from such substances.

Information about preparations containing oxidized cellulose can be found in the Preparation for usesection.

TISSEEL with food and drink

Ask your doctor. The doctor will decide whether the patient can eat and drink before using TISSEEL.

Pregnancy, breastfeeding, and fertility

If you are pregnant or breastfeeding, think you may be pregnant, or plan to have a child, consult your doctor or pharmacist before using this medicine. The doctor will decide whether TISSEEL can be used during pregnancy or breastfeeding.

Driving and using machines

TISSEEL has no effect on the ability to drive vehicles or operate machinery.

TISSEEL contains Polysorbate 80

Polysorbate 80 may cause local skin reactions, such as contact dermatitis.

3. How to use TISSEEL

The TISSEEL product can only be used by experienced surgeons who have been trained in this regard.

Before applying the TISSEEL product, the wound surface should be dried using standard techniques (e.g., changing compresses, gauzes, using suction devices).

Compressed air or gas should not be used to dry the surface.

TISSEEL can only be sprayed on visible surfaces.

When applying the TISSEEL product using a spray device, follow the manufacturer's recommendations for pressure and distance from the tissue in accordance with the ranges specified below:

During spraying of the TISSEEL product, monitor changes in blood pressure, heart rate, arterial oxygen saturation, and end-tidal CO2 concentration due to the possibility of air or gas embolism (see section 2).

The dose of the applied glue is always determined based on individual needs.

The dose depends on a number of factors, including the type of surgical procedure, the size of the glued surface, the chosen method of applying the glue, and the number of applications. The doctor will decide how much is needed and apply a thin, even layer to the target surface. If the applied amount does not appear to be sufficient, the application of the glue can be repeated.

When applying the TISSEEL product, a clot forms quickly. Avoid applying a new layer on an existing layer of TISSEEL, as the new layer will not bind to the existing one. It is absolutely necessary to avoid separate application of the protein glue component and the thrombin component.

In clinical trials, individually adjusted doses administered ranged from 4 to 20 ml. In some procedures (e.g., traumatic liver injury or treatment of extensive burn wounds), it may be necessary to use larger volumes.

As a guideline for gluing surfaces, it can be assumed that 1 set of TISSEEL glue 2 ml (i.e., 1 ml of protein glue solution plus 1 ml of thrombin solution) is sufficient to cover an area of at least 10 cm².

When TISSEEL is applied by spraying, the same amount will be sufficient to cover a correspondingly larger surface area.

To avoid excessive granulation and to ensure gradual absorption of the solidified tissue glue, it is recommended to apply the thinnest possible layers of TISSEEL.

To ensure proper mixing of the protein glue solution and thrombin solution components, it is recommended to squeeze out the first few drops of the product from the application needle and immediately discard them before applying the product.

Using a higher dose of TISSEEL than recommended

TISSEEL is used only during surgical operations. The doctor determines the amount needed to be applied. There are no known cases of overdose.

If you have any questions about using the medicine, consult your doctor or pharmacist.

Use in children

The safety and efficacy of the medicine in children have not been established.

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everybody gets them.

If any of the side effects get serious or if you notice any side effects not listed in this leaflet, please tell your doctor or pharmacist.

In patients treated with tissue glue, hypersensitivity reactions or allergic reactions may occur.

Although they are very rare, they can be very serious.

The first signs of an allergic reaction may include:

• transient skin redness
• itching
• rash
• nausea, vomiting
• headache
• drowsiness
• restlessness
• burning and stinging at the injection site
• ringing in the ears
• chills
• chest tightness
• swelling of the lips, tongue, and throat (which can cause difficulty breathing and/or swallowing)
• breathing difficulties
• low blood pressure
• increase or decrease in heart rate
• loss of consciousness due to a drop in blood pressure

In individual cases, these reactions can develop into severe allergic reactions (anaphylaxis).

Such reactions can occur especially when the preparation is used repeatedly or is administered to patients who have previously shown hypersensitivity to aprotinin or any other component of the product.

Even if previous multiple uses of TISSEEL were well tolerated, subsequent administration of TISSEEL or injection of aprotinin may lead to severe allergic reactions (anaphylactic).

The surgical team is aware of the risk of this type of reaction, and if the first signs of hypersensitivity appear, the administration of TISSEEL will be stopped immediately. Severe symptoms may require emergency measures.

Injection of TISSEEL into soft tissues can cause local tissue damage.

Injection of TISSEEL into blood vessels (veins or arteries) can cause clot formation (thrombosis).

Because TISSEEL is manufactured from plasma derived from blood donors, the risk of infection cannot be completely ruled out.

However, the manufacturer takes numerous measures to reduce this risk (see section 2).

In rare cases, antibodies against the components of the tissue glue may appear.

The following side effects have been observed with TISSEEL treatment:

Side effects were assessed according to the following frequency categories:

Very common:may affect more than 1 in 10 people

Common:may affect up to 1 in 10 people

Uncommon:may affect up to 1 in 100 people

Rare:may affect up to 1 in 1,000 people

Very rare:may affect up to 1 in 10,000 people

Unknown:frequency cannot be estimated from the available data

*The occurrence of air or gas bubbles in the vascular system occurred when fibrin glues were applied using devices with compressed air or gas; this appears to be related to improper use of the spray device (e.g., at higher than recommended pressure and/or at a closer than recommended distance from the tissue surface).

Reporting side effects

If you experience any side effects, including any side effects not listed in this leaflet, tell your doctor or nurse.

Side effects can be reported directly to the

Department of Adverse Reaction Monitoring of Medicinal Products, Medical Devices, and Biocidal Products

Jerozolimskie Avenue 181C

02-222 Warsaw

Tel.: +48 22 49 21 301

Fax: +48 22 49 21 309

Website: https://smz.ezdrowie.gov.pl

Side effects can also be reported to the marketing authorization holder.

By reporting side effects, you can help provide more information on the safety of this medicine.

5. How to store TISSEEL

Keep this medicine out of the sight and reach of children.

Do not use this medicine after the expiry date stated on the label.

Store and transport in a frozen state (at a temperature of ≤-20°C) without interruption until use.

Store the syringe in the outer carton to protect it from light.

Storage after thawing:

The product in an unopened package and thawed at room temperature can be stored at room temperature (not exceeding 25°C) for up to 72 hours.

After thawing, the solution must not be refrozen or refrigerated.

Do not throw away any medicines via wastewater or household waste. Ask your pharmacist how to throw away medicines you no longer use. These measures will help protect the environment.

6. Package contents and other information

What TISSEEL contains

TISSEEL consists of two components:

Component 1: Protein glue solution

The active substances contained in 1 ml of protein glue solution are: human fibrinogen, 91 mg/ml, synthetic aprotinin, 3000 KIU/ml.

Other components are: human albumin, L-histidine, nicotinamide, disodium citrate dihydrate, polysorbate 80 (Tween 80), water for injections.

Component 2: Thrombin solution

The active substances contained in 1 ml of thrombin solution are: human thrombin, 500 IU/ml, calcium chloride dihydrate, 40 μmol/ml.

Other components are: human albumin, sodium chloride, water for injections.

TISSEEL contains human factor XIII, copurified with human fibrinogen, in amounts of 0.6–5 IU/ml.

What TISSEEL looks like and what the package contains

Solutions for tissue glue

The protein glue solution and thrombin solution are supplied in a plastic syringe for single use.

The frozen solutions are colorless to pale yellow, opalescent.

After thawing, the solutions are colorless to pale yellow.

TISSEEL is available in the following packaging:

Contents of the package with PRIMA syringe

1 ml, 2 ml, or 5 ml of protein glue solution and 1 ml, 2 ml, or 5 ml of thrombin solution in a dual-chamber syringe (polypropylene) closed with a stopper and packaged in two bags with a device consisting of 2 connectors and 4 application needles.

Contents of the package with AST syringe

1 ml, 2 ml, or 5 ml of protein glue solution and 1 ml, 2 ml, or 5 ml of thrombin solution in a dual-chamber syringe (polypropylene) closed with a stopper and packaged in two bags with a device consisting of 2 connectors, 4 application needles, and 1 double syringe plunger.

Package size

TISSEEL is available in the following package sizes: 1x 2 ml (1 ml + 1 ml), 1 x 4 ml (2 ml + 2 ml), and 1 x 10 ml (5 ml + 5 ml).

The solutions are frozen.

Not all types of packaging may be available.

Marketing authorization holder and manufacturer

Marketing authorization holder:

Baxter Polska Sp. z o.o.

Kruczkowskiego Street 8

00-380 Warsaw

Manufacturer

Takeda Manufacturing Austria AG

Industriestrasse 67

1221 Vienna, Austria

This medicinal product is authorized in the Member States of the European Economic Area under the following names:

Austria:

TISSEEL - Solutions for tissue glue

Bulgaria:

ТИСИЛ - разтвори за тъканно лепило

Czech Republic:

TISSEEL - solutions for glue

France:

TISSEEL - solutions for glue

Germany:

TISSEEL 2 ml

TISSEEL 4 ml

TISSEEL 10 ml

Greece:

TISSEEL - Διαλύματα για στεγανοποιητικό

Malta:

TISSEEL - Solutions for sealant

Norway:

TISSEEL

Poland:

TISSEEL

Slovakia:

TISSEEL - fibrin glue

Spain:

TISSEEL - soluciones para adhesivo tisular

Date of last revision of the leaflet: January 2022

Information intended for healthcare professionals only (PRIMA syringe package):

General information

• Before applying TISSEEL, protect the areas of the body outside the target application site to avoid gluing tissues in undesirable locations.
• To prevent the glue from sticking to gloves and surgical instruments, moisten them with a physiological saline solution before coming into contact with them.
• As a guideline for gluing surfaces, it can be assumed that 1 set of TISSEEL glue 2 ml (i.e., 1 ml of protein glue solution plus 1 ml of thrombin solution) is sufficient to cover an area of at least 10 cm².
• The required dose depends on the size of the glued surface.
• DO NOT use the two components of the TISSEEL product separately. Both components must be used together.
• Do not expose the TISSEEL product to temperatures above 37°C. DO NOT heat it in a microwave.
• DO NOT thaw the product by holding it in your hands.
• DO NOT use the TISSEEL product until it has been completely thawed and warmed to a temperature of 33°C - 37°C.
• Remove the protective cap from the syringe only after thawing and warming. To facilitate removal of the protective cap from the syringe, move the protective cap back and forth and then remove the protective cap from the syringe.
• Remove all air from the syringe and then attach the connector and application needle.

Preparation for use

The protein glue solution and thrombin solution are contained in a ready-to-use syringe. The product is packaged under aseptic conditions in two sterile bags. The inner bag and its contents are sterile, unless the integrity of the outer package has been compromised. Using aseptic technique, transfer the sterile inner bag and its contents to a sterile area.

The ready-to-use syringe can be thawed and warmed using one of the following methods:

• 1. Rapid thawing/warming (sterile water bath) – recommended method
• 2. Thawing/warming in a non-sterile water bath
• 3. Thawing/warming in an incubator
• 4. Thawing at room temperature (not exceeding 25°C) BEFORE warming

Instructions:

Place the inner bag in a sterile water bath at a temperature of 33°C - 37°C. Ensure that the contents of the ready-to-use syringe are completely submerged in water.

Table 1 – PRIMA syringe: minimum thawing/warming time in a sterile water bath

• 2) Thawing/warming in a non-sterile water bath

Instructions:

Place the ready-to-use syringe in both protective bags in a water bath outside the sterile area for the appropriate time (see Table 2). Ensure that the bags remain submerged in water during the entire thawing time. After thawing, remove the bags from the water bath, dry the outer bag, and transfer the inner bag with the ready-to-use syringe and plunger to the sterile area.

Table 2 - PRIMA syringe: Minimum thawing/warming time in a non-sterile water bath

• 3) Thawing/warming in an incubator

Instructions:

Place the ready-to-use syringe in both protective bags in an incubator outside the sterile area for the appropriate time (see Table 3). After thawing/warming, remove the bags from the incubator, remove the outer bag, and transfer the inner bag with the ready-to-use syringe to the sterile area.

Table 3 – PRIMA syringe: Minimum thawing/warming time in an incubator

• 4) Thawing at room temperature (not exceeding 25°C) BEFORE warming

Instructions:

Thaw the ready-to-use syringe in both protective bags at room temperature outside the sterile area for the appropriate time (see Table 4). After thawing, to warm the product for use, warm it in the outer bag in an incubator.

Table 4 – PRIMA syringe: Minimum thawing time at room temperature outside the sterile area and additional warming time, in an incubator to a temperature of 33°C to 37°C

After thawing at room temperature, the product must be used within 72 hours of removal from the freezer.

Stability after thawing

After thawing and warming(at a temperature of 33°C to 37°C, methods 1, 2, and 3), the chemical and physical stability of the product has been demonstrated for 12 hours at a temperature of 33°C to 37°C.

For the product thawedat room temperature, in an unopened bag (method 4), the chemical and physical stability of the product has been demonstrated for 72 hours at a temperature not exceeding 25°C.

Warm to a temperature of 33°C to 37°C immediately before use.

From a microbiological point of view, the product should be used immediately after warming to a temperature of 33°C to 37°C, unless the opening/thawing method excludes the risk of microbiological contamination.

If the product is not used immediately, the user is responsible for the storage time and conditions.

Do not refreeze or refrigerate after starting thawing.

Handling the product after thawing/before administration

To achieve optimal mixing of the two solutions and optimal coagulation of the fibrin glue, the temperature of both components of the glue should be maintained at 33°C - 37°C until application.

The protein glue solution and thrombin solution should be clear or slightly opalescent. Do not use cloudy solutions or those containing sediment. Thawed products should be visually inspected for the presence of insoluble particles and changes in color or any change in physical appearance before use. If any of these situations occur, the solution should be discarded.

The thawed protein glue solution should be a slightly viscous liquid. If the solution has the consistency of a solidified gel, it should be suspected that it has denatured (probably due to a break in the cold chain during storage or overheating during warming). In this case, DO NOT use TISSEEL under any circumstances.

• Do not remove the dual-chamber syringe from the plastic bag until use.
• Use TISSEEL only after complete thawing and warming (liquid consistency).
• Remove the protective cap from the syringe only immediately before application. To facilitate removal of the protective cap from the syringe, move the protective cap back and forth and then remove the protective cap from the syringe.

Administration using the PRIMA syringe:To apply the glue, connect the dual-chamber ready-to-use syringe filled with the protein glue solution and thrombin solution to the connector and application needle provided in the attached device set. The common plunger of the dual-chamber ready-to-use syringe ensures that equal volumes of both components are administered to the connector, which are then mixed in the application needle and applied.

Safety strap

Double plunger

Dual-chamber syringe

Connector

Application needle

• Remove all air from the syringe and then attach the connector and application needle.
• Position the connector and secure it to the side of the syringe with the safety strap.
• Connect the outlets of the dual-chamber ready-to-use syringe to the connector, ensuring they are properly secured.
• Secure the connector by fastening the safety strap to the ready-to-use dual-chamber syringe.
• If the safety strap is broken, use the additional connector included in the set.
• If there is no additional connector, the set can still be used if attention is paid to ensuring that the connection is secure and tight.
• DO NOT remove air from the connector.
• Attach the application needle to the connector.
• DO NOT remove air from the connector or application needle before starting the actual application of the glue, as this may cause the needle to become clogged.

Administration

Before applying the TISSEEL product, dry the wound surface using standard techniques (e.g., changing compresses, gauzes, using suction devices).

Compressed air or gas should not be used to dry the surface.

• Apply the mixed protein glue-thrombin solution to the target surface or surfaces to be glued, slowly pressing the rear part of the common plunger.
• In surgical procedures that require minimal amounts of fibrin glue, it is recommended to express and discard the first few drops of the product.
• After applying TISSEEL, wait at least 2 minutes to achieve sufficient polymerization.

The translation of the provided HTML content is complete, and all medical terminology has been preserved to ensure accuracy.

Warning:

If the application of the fibrin sealant components is interrupted, the needle may become immediately clogged. In such a case, the application needle should be replaced with a new one only directly before reapplying the sealant. If the connector outlets are clogged, an additional connector provided in the packaging should be used. After mixing the fibrin sealant components, its coagulation occurs within a few seconds - due to the high concentration of thrombin (500 IU/ml). The fibrin sealant can also be applied using other devices manufactured by BAXTER, which are specifically designed for use in endoscopy, minimally invasive surgical procedures, or for applying the preparation to large or hard-to-reach surfaces. When using such devices, the instructions for their operation must be strictly followed. Preparations containing oxidized cellulose should not be used with the TISSEEL product, as the low pH affects the activity of thrombin. For certain applications, biocompatible materials such as collagen patches can be used as a carrier or for mechanical reinforcement of the bonds.

Applying the product using a spray device

When applying the TISSEEL product using a spray device, the manufacturer's recommendations regarding pressure and distance from the tissue should be followed, in accordance with the ranges provided below:

During the spraying of the TISSEEL product, changes in arterial pressure, pulse, arterial blood oxygen saturation, and end-expiratory CO2 concentration should be monitored due to the possibility of air or gas embolism (see point 2).

In the case of administering the TISSEEL product in a closed chest or abdominal cavity, the use of the DuploSpray MIS applicator and control system is recommended. Further information is provided in the DuploSpray MIS device instruction manual.

Removal of residues

Any unused remains of the medicinal product or its waste should be disposed of in accordance with local regulations.

Information intended exclusively for professional medical personnel (packaging: AST syringe):

General information

• Before applying TISSEEL, the body areas outside the target application site should be protected to avoid unwanted tissue adhesion.
• To prevent the glue from sticking to gloves and surgical instruments, they should be moistened with a physiological saline solution before contact.
• As a guideline for gluing surfaces, it can be assumed that 1 set of TISSEEL 2 ml (i.e., 1 ml of protein solution plus 1 ml of thrombin solution) is sufficient to cover an area of at least 10 cm².
• The required dose depends on the size of the glued surface.
• DO NOT use the two components of the TISSEEL product separately. Both components must be used together.
• DO NOT expose the TISSEEL product to temperatures above 37°C. DO NOT subject it to microwave radiation.
• DO NOT thaw the product by holding it in your hands.
• DO NOT use the TISSEEL product until it has been completely thawed and warmed to a temperature of 33°C - 37°C.
• Remove the protective cap from the syringe only after thawing and warming have been completed.
• Remove all air from the syringe and then attach the connector and application needle.

Preparation for use

The protein solution and thrombin solution are contained in a ready-to-use syringe. The product is packaged under aseptic conditions in two sterile bags. The inner bag and its contents are sterile unless the integrity of the outer packaging has been compromised. Using sterile technique, transfer the sterile inner bag and its contents to a sterile area.
The ready-to-use syringe can be thawed AND warmed using one of the following methods:

• 1. Rapid thawing/warming (sterile water bath) – recommended method
• 2. Thawing/warming in a non-sterile water bath
• 3. Thawing/warming in an incubator
• 4. The ready-to-use syringe can also be thawed and stored at room temperature (not exceeding 25°C) for a maximum of 72 hours. Before use, warming is required.
• 1) Rapid thawing/warming (sterile water bath) – recommended method

It is recommended to thaw and warm both components of the sealant using a sterile water bath at a temperature of 33°C – 37°C.

• The water bath temperature should not exceed 37°C. To control the specified temperature range, the water temperature should be continuously checked with a thermometer, and the water replaced as needed.
• If a sterile water bath is used for thawing and warming, remove the syringe from the bag before placing it in the sterile water bath.

Instruction:

Transfer the inner bag to a sterile environment, remove the ready-to-use syringe from the inner bag, and place it directly in a sterile water bath. Ensure that the contents of the ready-to-use syringe are completely submerged in water.
Table 1 – AST syringe: minimum thawing and warming time in a sterile water bath
Minimum thawing/warming time
Package size
33°C to 37°C, sterile water bath
product removed from bags
2 ml
5 minutes
4 ml
5 minutes
10 ml
12 minutes

• 2) Thawing/warming in a non-sterile water bath

Instruction:

Place the ready-to-use syringe in both protective bags in a water bath outside the sterile area for the appropriate time (see Table 2). Ensure that the bags remain submerged in water during the entire thawing time. After thawing, remove the bags from the water bath, dry the outer bag, and transfer the inner bag with the ready-to-use syringe and plunger to a sterile area.
Table 2 - AST syringe: Minimum thawing and warming time in a non-sterile water bath
Minimum thawing/warming time
Package size
33°C to 37°C, non-sterile water bath
product in bags
2 ml
30 minutes
4 ml
40 minutes
10 ml
80 minutes

• 3) Thawing/warming in an incubator

Instruction:

Place the ready-to-use syringe in both protective bags in an incubator outside the sterile area for the appropriate time (see Table 3). After thawing/warming, remove the bags from the incubator, remove the outer bag, and transfer the inner bag with the ready-to-use syringe to a sterile area.
Table 3 – AST syringe: Minimum thawing and warming time in an incubator
Minimum thawing/warming time
Package size
33°C to 37°C, incubator
product in bags
2 ml
40 minutes
4 ml
85 minutes
10 ml
105 minutes

• 4) Thawing at room temperature (not exceeding 25°C) BEFORE warming

Instruction:

Thaw the ready-to-use syringe in both protective bags at room temperature outside the sterile area for the appropriate time (see Table 4). After thawing, to warm the product for use, warm it in the outer bag in an incubator.
Table 4 – AST syringe: Minimum thawing time at room temperature outside the sterile area and additional warming time in an incubator to a temperature of 33°C to 37°C
Warming time before use
Minimum thawing time
to a temperature of 33°C to
maximum 37°C in an incubator
after thawing at room temperature
product in outer bag
product in outer bag
Package size
2 ml
60 minutes
+ 15 minutes
4 ml
110 minutes
+ 25 minutes
10 ml
160 minutes
+ 35 minutes
After thawing at room temperature, the product must be used within 72 hours of removal from the freezer.

Stability after thawing

After thawing and warming (at a temperature of 33°C to 37°C, methods 1, 2, and 3), the chemical and physical stability of the product has been demonstrated for 12 hours at a temperature of 33°C to 37°C.
For the product thawed at room temperature, in an unopened bag (method 4), the chemical and physical stability of the product has been demonstrated for 72 hours at a temperature not exceeding 25°C.
Warm to a temperature of 33°C to 37°C immediately before use.
From a microbiological point of view, the product should be used immediately after warming to a temperature of 33°C to 37°C, unless the opening/thawing method excludes the risk of microbiological contamination.
If the product is not used immediately, the user is responsible for the time and conditions of storage.
Do not refreeze or refrigerate after starting thawing.

Handling the product after thawing/before administration

To achieve optimal mixing of the two solutions and optimal coagulation of the fibrin sealant, the temperature of both sealant components should be maintained at 33°C - 37°C until application.
The protein solution and thrombin solution should be clear or slightly opalescent. Do not use cloudy solutions or those containing sediment. Thawed products should be visually inspected for the presence of insoluble particles and changes in color or any change in physical appearance before use. If any of these situations occur, the solution should be discarded.
The thawed protein solution should be a slightly viscous liquid. If the solution has the form of a solid gel, it should be assumed that it has denatured (probably due to a break in the cold chain or overheating during warming). In such a case, TISSEEL MUST NOT be used under any circumstances.

• Do not remove the syringe from the bag until use.
• Use TISSEEL only after complete thawing and warming (liquid consistency).
• Remove the protective cap from the syringe only immediately before application.

Administration using the AST syringe:To apply the sealant, connect the dual-chamber ready-to-use syringe filled with the protein solution and thrombin solution to the connector and application needle provided in the attached instrument set. The common plunger of the dual-chamber ready-to-use syringe, provided in the set of application devices, ensures the administration of equal volumes of both components, which are then mixed in the application needle and applied.
AST syringe operating instructions

• Remove all air from the syringe, and then attach the connector and application needle.
• Set the connector and secure it to the side of the syringe with a safety strap.
• Connect the outlets of the dual-chamber ready-to-use syringe to the connector, ensuring they are properly secured.
• Secure the connector by attaching the safety strap to the ready-to-use dual-chamber syringe.
• In the event of a broken safety strap, use the additional connector provided in the set.
• If there is no additional connector, the set can still be used if care is taken to ensure the connection is secure and leak-tight.
• DO NOT remove air from the connector.
• Attach the application needle to the connector.
• DO NOT remove air from the connector or application needle before starting the actual application, as this may cause the needle to become clogged.

Administration

Before applying the TISSEEL product, the wound surface should be dried using standard techniques (e.g., changing compresses, gauzes, using suction devices).
Compressed air or gas should not be used to dry the surface.

• Apply the mixed protein-thrombin solution to the target surface or surfaces to be bonded, slowly pressing the rear part of the common plunger.
• In surgical procedures that require the use of minimal amounts of fibrin sealant, it is recommended to express and discard the first few drops of the product.
• After applying TISSEEL, wait at least 2 minutes to achieve sufficient polymerization.

Warning:

If the application of the fibrin sealant components is interrupted, the needle may become immediately clogged. In such a case, the application needle should be replaced with a new one only directly before reapplying the sealant. If the connector outlets are clogged, an additional connector provided in the packaging should be used. After mixing the fibrin sealant components, its coagulation occurs within a few seconds - due to the high concentration of thrombin (500 IU/ml). The fibrin sealant can also be applied using other devices manufactured by BAXTER, which are specifically designed for use in endoscopy, minimally invasive surgical procedures, or for applying the preparation to large or hard-to-reach surfaces. When using such devices, the instructions for their operation must be strictly followed. Preparations containing oxidized cellulose should not be used with the TISSEEL product, as the low pH affects the activity of thrombin. For certain applications, biocompatible materials such as collagen patches can be used as a carrier or for mechanical reinforcement of the bonds.

Applying the product using a spray device

Recommended pressure and distance values from the tissue and spray devices for applying the TISSEEL product

Spray set to be used
Końcówki aplikatora, które
Regulator ciśnienia, który
Zalecana odległość
od tkanki docelowej
Zalecane ciśnienie
rozpylania
Surgical treatment
ma być zastosowany
mają być zastosowane
ma być zastosowany
Tisseel/Artiss spray set
nd.
EasySpray
1.5–2.0 bar (21.5–28.5 psi)
Open wound
10–15 cm
Tisseel/Artiss spray set — packaging of 10 pieces
nd.
EasySpray
Regulator Duplospray MIS 1.5 bar
Aplikator Duplospray MIS 20 cm
Aplikator Duplospray MIS 30 cm
Aplikator Duplospray MIS 40 cm
Zestaw Spray Set 360 Aplikator endoskopowy z Snap Lock
Zestaw Spray Set 360 Aplikator endoskopowy z paskiem zabezpieczającym
Wymienna końcówka
1.2–1.5 bar (18–22 psi)
Laparoscopic/minimally invasive procedures
nd.
2–5 cm