Information for Distributors

Background to Tissuemed
• Tissuemed is a prominent medical device company based in Leeds, UK

• Founded by surgeons as a University spin-out (mid-1970’s)

• Initially focused on tissue heart valves and grafts

• Current R&D focus is on:

– Tissue Sealants / Contact Adhesives / Local Delivery
A few definitions of words you will see:
Haemostasis: Literally “static (still) blood”….slowing blood flow down will
result in it clotting (flow rate?). Haemostat….something that stops blood
flow.
Thrombogenic: Literally “clot-generating”…..so a thrombogenic
haemostat works by biochemically inducing a clotting reaction.
Thrombogenic materials are typically proteinaceous (collagen/fibrin).
Importantly Tissuepatch3 is NOT a thrombogenic haemostat…..it only induces clotting by virtue of its barrier
effect which slows blood flow to levels at which it will clot, which is why it is only indicated for mild to
moderate bleeds.

Covalent: Interaction between molecules resulting in a strong physical

bond.
Electrostatic: Lower level bonding between atoms carrying opposite
charges.
Autologous: Derived or transferred from the same individual’s body
Multilaminate: Many layered
The Product –Tissuepatch3
What is Tissuepatch3 ?

⇒Tissuepatch3

is a sealant and barrier film for the adjunctive prevention of air, blood
and/or fluid leakage in thoracic and general surgery

⇒Tissuepatch3

is a completely synthetic product. Unlike commonly used sealants and

haemostats it does not contain any human or animal derived materials.

What isn’t Tissuepatch3 ?

⇒Tissuepatch3

is not a thrombogenic haemostat. It is not designed to biologically induce

clotting and therefore will not stop significant bleeds.
Tissuepatch3 Description

• Thin film (≤40µm), flexible, integrated

tissue sealant, barrier and adhesive

• Made from absorbable synthetic materials

• Highly versatile

• Self-adhesive and tissue-bonding

• Dry and ready-to-use

Barrier laminate Cross section:

Sealant laminate overprinted with brand Adhesive, sealant

and barrier
Cohesive laminate properties provided
by fused laminate
Sealant and Adhesive laminate structure preformed
in manufacture
Product Advantages
⇒ Cost-Effective: Reduced OR time, tissue support during wound
healing, and reduced hospital stay.

⇒ Broad Sealing: Self-adhesive patch that forms a blood/fluid/air

tight seal

⇒ Strong: Strong adhesion with cross linking in situ.

⇒ Flexible/Elastic: Can be applied to non-uniform surfaces.

⇒ Easy to Use: “Open and Apply”.

No guns, no cartridges, no preparation required,
Bonds to surgical site in <30 seconds.

⇒ Synthetic: Constructed from synthetic polymers.

No human or animal material.
Gamma-sterilized. Absorption in about 50 days.

⇒ Approvals: CE mark approved

Indication

Tissuepatch3 is indicated for use to seal and reinforce against:

⇒ air leakage in thoracic surgery, e.g. lung resection

⇒ leakage of low pressure or oozing bleeding in general surgery

Tissuepatch3 is intended for use as an adjunct in thoracic and general

surgery. It is not intended to replace sutures or staples.

When bleeding or air leak cannot be controlled with conventional

methods, Tissuepatch3 can be applied to a wound to seal the area
effectively within 30 seconds.
Mechanism of action

Tissuemed’s patented polymer technology enables Tissuepatch3 to bond

to a range of tissue surfaces in a two-stage process.
Preclinical efficacy

The preclinical efficacy of

Tissuepatch3 has been
demonstrated using two
surgical models:

• Thoracic

• General

Both show Tissuepatch3 to be

an effective treatment for the
sealing of air and blood leaks.
Thoracic surgery model

• Porcine lung (n=6)

• Punch biopsy to create pleural defect
• Acute air leak grading
• 14 and 28 day recovery
Thoracic surgery model

t ≤ 30 minutes t =14 days

General surgery model

• Rabbit liver (n=9)

• Punch biopsy to create low rate bleed
• Acute blood loss collection
• 1, 2 and 4 month recovery
General surgery model

t < 10 minutes t = 2 months

Clinical performance -
History

Tissuepatch3 is based on the

clinically proven benefits of
Tissuepatch2, while offering
improved flexibility and
conformance to tissue.

Tissuepatch2, has been used

clinically by thoracic surgeons.
This product, using Tissuemed’s
adhesive polymer as a dry powder
has been shown to be effective in
reducing air leaks.
Clinical performance – Tissuepatch2

Multi-Centre Clinical Investigation to Evaluate the Safety

and Performance of Tissuepatch2 in the Prevention of Air
Leaks Following Lung Resection

• Target population: Patients undergoing lung resection

• Two centre study with 3 Clinical Investigators

• Patient treatment completed - 17

• Follow-up - 6 weeks, 3 and 6 months

Clinical performance – Tissuepatch2

• Easy to handle and apply ➼

• Immediate and sustained reduction in air leaks ➼

• Normal fluid discharge and patient recovery ➼

• Early removal of chest drain(s) (107 hrs v 125-166 hrs) ➼

• Early hospital patient discharge (6 days v 10-14 days) ➼

• No device related adverse events ➼

• Strong surgeon endorsement

Tiss uemed Op in io n:
Tiss uep atch 2 has p ro ven ef ficacy and safety .
Tiss uep atch 3 is e xp ected to maxi mise al read y ver y sub stant ial comp etitive a dvantag es
Clinical performance – Tissuepatch2

• Tissuepatch2 performs better than Tachosil (Nycomed).

• Tissuepatch3 is expected to offer further improvements

Clinical performance – Tissuepatch3

A Post-Market Surveillance Study of the Safety and

Performance of Tissuepatch3 in the Prevention of Air Leaks
Following Lung Surgery

• Target population: Patients undergoing lung surgery

• Two centre study with 2 Clinical Investigators

• Patients to be treated - 20

• Follow-up - 6 weeks and 3 months

Comments to Date: “Extremely Good First Impressions”

Matrix of competitive sealant products used in Lung Surgery
Company Product Product Selling Source/Material Preparation/ Efficacy Comments
Type price* Application time (Reason)

Baxter Tisseel Liquid £200 Human/Animal Preparation Time – 15-20 mins*** Low(Strength) Haemostat action
Application Time – 1-2 mins greater than
sealant effect

CSL Behring Beriplast Liquid £200 Human/Animal Preparation Time – 15-20 mins*** Low(Strength) Haemostat action
/Nycomed Application Time – 1-2 mins greater than
sealant effect

Ethicon/Omrix Quixil/ Liquid £200 Human Preparation Time – 15-20 mins*** Low(Strength) Haemostat action
Crosseal Application Time – 1-2 mins greater than
sealant effect

CryoLife BioGlue Liquid £190 Animal Preparation Time – 2-3 mins Low(Weak adhesion) Cytotoxicity
Application Time – 1-2 mins concerns relating
to glutaraldehyde
component

Nycomed Tachosil / Sheet £209 Human/Animal Preparation Time – 2-3 mins ** Medium(Slow/Weak adhesion) Poor surface-
Tachocomb Application Time – 3-5 mins ** conformance

Thermogenesis CryoSeal Liquid £160 Autologous Preparation Time – 60 mins** Low(Strength) Requires
Application Time – 1-2 mins** processing unit to
convert patients
blood to product

Vivolution Vivostat Liquid £160 Autologous Preparation Time – 30 mins** Low(Strength) As CryoSeal
Application Time – 1-2 mins**

Confluent DuraSeal Liquid £220 Synthetic Preparation Time – 1-2 mins Low(Strength,Short duration)
Surgical Application Time – 1-2 mins

Genzyme FocalSeal Liquid £180 Synthetic Preparation Time – 2-4 mins*** Low(Strength/Short duration) Requires light
Application Time – 5-10 mins source

Tissuemed Tissuepatch3 Film £200 Synthetic Preparation Time – 0 mins High (Contact surface
Application Time – 30 secs/patch chemistry, duration of effect)

* Equivalent per 5cm x 5cm patch

** Company information *** Report entitled Topical Hemostats in Surgery; Mary Jo Drew MD 2003

All liquid sealants require applicators or spray systems…..prices not included as this may be provided Free of Charge
General comment: Unlike Tissuepatch3 none of the listed products, excluding FocalSeal, was originated based on the lung application, which explains their
generally low acceptance.
Fibrin-based Liquids(Tisseel, Beriplast, Quixil)

•Typically require “mixing” up to 20 minutes prior to application

•Need time (1-2 minutes) to work

•Have low intrinsic strength

•Require careful application and may be difficult to apply uniformly to

target tissue

•Are derived from human/animal sources

•Have a haemostatic rather than adhesive sealant effect

Synthetic Liquids (Duraseal, Focalseal)

•Typically require “mixing” a few(1-2) minutes prior to application

•Need time to apply (Focalseal – 5-10 minutes) and work (1-2 minutes)

•Have low intrinsic strength

•Require careful application and may be difficult to apply uniformly to

target tissue

•Have low duration of effect because of their chemistry

•In the case of Focalseal requires a Light source to

activate.
 Autologous “sealants” (Cryoseal, Vivostat)

•Require extended preparatory process involving blood removal from

patient 30-60 minutes prior to application

•Need time (1-2 minutes) to work

•Have low intrinsic strength

•Require careful application and may be difficult to apply uniformly to

target tissue

•Have low adhesion, acting primarily as haemostats

•Requires significant hardware

 Sheet-type haemostats
(Tachosil,Tachocomb)

•Require preparation (2-3minutes)

•Need time (3-5 minutes) to work

•Are derived from human/animal proteins

•Have low adhesion

•Are bulky and have poor “conformability”

Questions and Answers
What is Tissuepatch3?
Tissuepatch3 is a self adhesive surgical sealant and barrier. It is a thin flexible
film supplied in three sizes; small (25mm × 50mm), medium (50mm × 50mm)
and large (50mm × 100mm). Tissuepatch3 is 40 microns (0.04mm) thick.

What procedures is Tissuepatch3 indicated for?

Tissuepatch³ is indicated for use to seal and reinforce against air leakage in
thoracic surgery, and against leakage of low pressure or oozing bleeding or fluid
leakage following surgical procedures on soft tissue. Tissuepatch³ is intended for
use as an adjunct in thoracic and general surgery and is not intended to replace
sutures or staples, as appropriate, in tissue approximation.

How does Tissuepatch3 work?

Upon application Tissuepatch3 immediately adheres to the surface by a
combination of electrostatic and covalent bonding.

How adhesive is Tissuepatch3?

The adhesive strength of Tissuepatch3 is significantly higher (×100) than that of
commonly used haemostats (e.g. Tisseel) and sealants (e.g. CoSeal).
Questions and Answers
Does Tissuepatch3 contain animal/human derived material?
No – Tissuepatch3 is entirely synthetic.

What are the storage conditions for Tissuepatch3?

Tissuepatch3 should be stored at 2-8°C. It should not be frozen. The product
currently has a shelf life of 17 months.

How is Tissuepatch3 packaged?

For each product size, a single device is packaged within a sterile paper/plastic
inner pouch, which is further sheathed in an outer foil pouch the outside of which
is NON-STERILE.

Can Tissuepatch3 be cut to shape?

Yes – Tissuepatch3 can be cut to shape with sterile scissors. Handling, especially
of the contact surface should be minimised and it should be kept dry.

Should Tissuepatch3 be applied dry or wet?

Tissuepatch3 should remain dry until applied. Wetting will affect adhesion
performance.
Questions and Answers

How should Tissuepatch3 be applied?

Before application the site should be wiped to remove excess blood/fluid. With the
“TP 3” text readable, pressure should be exerted across the patch using a dry swab
for at least 30 seconds.

Can Tissuepatch3 be removed?

If Tissuepatch3 has been applied incorrectly or has not adhered it may be removed
within the first few minutes of application. The tissue may be prepared for
application of a new patch.

How large a patch should I use?

During application there should be a 1cm margin between the injury and the edge
of the Tissuepatch3 applied. When treating large injuries Tissuepatch3 may be
overlaid.

Is there a limit to how many patches can be applied?

Preclinical data supports the safe use of up to 8 small (25mm × 50mm × 0.04mm),
4 medium (50mm × 50mm × 0.04mm) and 2 large (50mm × 100mm × 0.04mm)
patches.
Questions and Answers
Can Tissuepatch3 be resterilised?
No – Tissuepatch3 is a sterile single patient use medical device. Once opened
Tissuepatch3 should be kept dry and used within 6 hours, after which it should be
discarded.

Can Tissuepatch3 be removed?

If Tissuepatch3 has been applied incorrectly or has not adhered it may be removed
within the first few minutes of application. The tissue may be prepared for
application of a new patch.

Are there any contra-indications for use?

Tissuepatch3 should not be used on patients with a known allergy to its
constituents. It should not be used to seal defects in neurological applications. It is
not for intravascular use.

What is the “TP 3” logo for?

Tissuepatch3 should be applied so the “TP 3” logo can be read.

Is Tissuepatch3 biodegradable?
Tissuepatch3 remains in position covered in a thin fibrous cover and it slowly
degrades until resorbed in ≈ 50 days.
In conclusion…..a few soundbites

•Because of its construction and contact surface chemistry

Tissuepatch3 is the most effective product available for
prevention of air leakage in lung surgery

•Tissuepatch3 requires no advance preparation, mixing,

soaking or extended contact apposition…..it requires the
least amount of preparation and application time of all
available products, being truly “open and apply”

•Tissuepatch3 is the easiest product to handle and apply to

the target tissue.