Application for Listing of
Suprasorb C®
in Part IX of the Drug Tariff
Activa Healthcare Ltd.
1, Lancaster Park, Newborough Road
Needwood, Burton-upon-Trent
Staffordshire DE13 9PD
Date of preparation:
July 2012
1
Table of contents
1. Introduction .......................................................................................................... 3
2. Suprasorb® C ....................................................................................................... 4
2.1. Unique manufacturing process ............................................................................ 6
2.2. Criteria for inclusion of Suprasorb® C in Part IX ................................................... 9
3. Indications for the use of Suprasorb® C................................................................ 9
3.1. Venous leg ulcers............................................................................................... 10
3.2. Pressure ulcers .................................................................................................. 10
3.3. Diabetic foot ulcers............................................................................................. 11
4. Clinical evidence for Suprasorb® C .................................................................... 12
5. Cost implications of Suprasorb® C ..................................................................... 23
6. Summary............................................................................................................ 24
7. Reference List .................................................................................................... 25
2
1. Introduction
In the UK chronic wounds represent a high medical and financial burden to patients
and the NHS (Posnett and Franks 2003). The impact of a chronic wound on patients´
quality of life is well documented (Franks and Morgan 2003). Chronic wounds include
pain, exudate and odour, and these symptoms are frequently associated with poor
sleep, loss of mobility and social isolation. Wound care is also a high cost area for the
NHS in time and costs in the hospital and in ambulatory care. The cost to the NHS of
caring for patients with a chronic wound is conservatively estimated at £2.3bn–3.1bn
per year, around 3% of the total estimated out-turn expenditure on health (£89.4bn)
for the same period (Posnett and Franks 2008). The problem of delayed healing of
chronic wounds highlights the importance of effective diagnosis and appropriate
treatment.
It is known that the components of chronic wound exudate have a detrimental effect
on wound healing. Therefore it is important to remove the exudate, whilst still
maintaining a moist wound environment (Andriessen 2003). Collagen is the most
important protein in human skin. The fibres form a very dense network, giving the
skin its strength. Collagen is a fibrous protein, synthesised in several stages. Its
precursors are assembled from amino acids in the endoplasmic reticulum of the
fibroblast. These protocollagen chains are twisted together in the Golgi complex.
Golgi vesicles transport the molecules to the cell membrane, where they are released
soluble tropocollagen into the intercellular space. Here they accumulate to form
protofibrils, which polymerise into microfibrils, which then unite into collagen fibers.
Collagen synthesis is dependent on the presence of ascorbic acid. This fibrous and
insoluble collagen is a promising material for biodegradable drug matrices.
The idea of using collagen in the treatment of wounds developed during the 1990s.
For the treatment of problem (or poorly healing) wounds, the focus should be on the
systemic prevention of exudate, the removal of exudate and the deactivation of
exudate components. At the same time, modulation of the cells to withstand exudate
toxicity can be attempted, to aid wound healing (Andriessen 2003, Vin et al. 2002,
Veves et al. 2002).
3
Biochemical imbalance may be the reason why the wound bed may look healthy and
yet the wound does not heal. This could be due to the presence of senescent cells or
cells of the wrong phenotype (Schönfelder et al. 2004a, Andriessen 2003, VaselBiergans et al. 2003). Poorly healing chronic wounds, e.g. diabetic or venous ulcers,
contain elevated levels of proteases (White et al. 2009, Andriessen 2003). The
overproduction of proteolytic enzymes leads to considerably reduced concentrations
of growth factors and proteinase inhibitors. An imbalance between degradation and
remodelling processes may cause poorly healing chronic wounds to persist in the
inflammatory phase and often to fail to heal for months or even years (Hollister et al.
2007, Andriessen 2003, Schönfelder et al. 2004a). Non-healing chronic wounds
contain significantly higher concentrations of inflammatory cytokines as IL-1ß, IL-6,
IL-8, and TNF-α (Wiegand et al. 2010). Collagen is an essential component of the
skin and is a fibrous protein synthesised in several stages.
2. Suprasorb® C
Suprasorb® C Collagen Wound Dressing consists of collagen of bovine origin. The
dressing has a porous structure with highly pronounced capillary activity, enabling it
to absorb fluid. This physical property with the continuous absorption of exudate
results in the intake of cell debris (such as necrotic tissue and fibrinous coating) as
well as inflammation inducing proteases and cytokines. Thereby the formation of
granulation tissue is supported and accelerated. Immigration of fibroblasts is induced
and collagen synthesis is stimulated. During the granulation stage and at the
beginning of the epithelisation stage, the continuous supply of the defect with high
grade collagen supports the new formation of the body’s own collagen fibrils and
fibres. The repair of the wound base supports the necessary proliferation and the
migration of epidermal cells. This assists wound healing (Instructions for use 2010).
Suprasorb C

Accelerates wound healing in all 3 phases

It binds factors which inhibit wound healing

It protects growth factors
4

It enhances haemostasis

It is easy to use
Tissue of animal origin
Suprasorb C is made of collagen sponges of frozen calves skin. The sourcing,
collection and handling of the material is in accordance with ISO 22442-2. The calves
used for collection must not be older than 12 month and must be from Australia. Each
delivery is provided with the appropriate health certificates according 2007/2006/EC
and 1774/2002/EC.
Indications
For application to wounds with extensive tissue damage, e.g. burns, surgical wounds,
skin donor sites, ulcers of various origin and wound cavities, in particular upon
stagnating wound conditions which are not responding to traditional dressing
(Instructions for use 2010).
Contraindication
Do not use Suprasorb® C in clinically infected areas (Instructions for use 2010).
Precautions

Interactions with other Preparations: Suprasorb® C Collagen Wound Dressing
should not be combined with antiseptics which release chlorine (e.g.
chloramine), with albumin-precipitating substances (tannic acid, silver nitrate)
or caustics (iodine tincture) which change proteins. Disinfectants and tanning
preparations are not to be applied in conjunction with Suprasorb® C Collagen
Wound Dressing.

Side-effects are not known in the case of correct use of Suprasorb ® C
Collagen Wound Dressing.

The product may not be used in the presence of known allergies to one or
several of its components (Instructions for use 2010).
5
Classification
Suprasorb® C Collagen Wound Dressing is intended to come into contact with injured
skin and is manufactured from animal tissues (collagen). Suprasorb ® C Collagen
Wound Dressing, sterile, is therefore classified as belonging to medical devices class
III, in accordance with rule 17 of Directive 93/42/EEC, Annex IX, section III. (Directive
93/42/EEC).
2.1.
Unique manufacturing process
Collagens are a large family of triple helical proteins which are distributed
throughout the body and which are important for a variety of functions including
tissue scaffolding, cell adhesion, cell migration, angiogenesis, tissue morphogenesis
and tissue repair. There are 28 different collagens in the human body, within
collagen type I being the most abundant one.
Proteins are important for virtually all living matter functions. The proper structure and
folding of a protein define its native state. Only in the native state is a protein fully
biologically functional. Any significant alteration of their native state, biologically
inactivates the protein.
Denaturation is a process, which causes such alteration by inducing major changes
to its original spatial folding without altering its primary structure (e.g. by cleaving
peptide bonds). Denaturation of proteins maybe be induced by chemical or physical
treatment, e.g. by treating proteins with chemicals, such as strong acids or bases,
high concentration of inorganic salts, organic solvents like alcohol, or by exposing
them to heat or irradiation. When the three-dimensional structure of the protein is
disrupted, the molecules biological activity is effected in a negative way.
That is the main reason why Suprasorb® C is produced aseptically – sterilization
would alter the products molecule structure and thus the product performance.
Lohmann & Rauscher provides an unique manufacturing process for the collagen
dressing Suprasorb® C- Collagen type I and operates a special plant.
In comparison to other manufactures Lohmann & Rauscher offers an antiseptic
manufacturing process instead of radiosterilization, which destroys a lot of collagen
fibers. Due to the sensitive aseptic procedure the manufacturing process is able to
produce nearly 100% pure collagen.
6
Step 1

Frozen calves skin from an isolated stock in Australia is send to Neuwied /
Germany per airmail.
Step 2

Chemical-physical reprocessing of the calves skin

Process includes approximate 35 steps with microbiologically inactivation

Main process consists of preparatory treatment (mechanical-chemical)
pulp  depilate  incinerate

Inactivation
Split  inactivation rinse  neutralization

Cut
Step 3

Rehashed skin material is ready for suspension plant

homogenization process starts

a water collagen slurry occurs
Step 4

filling process starts

we provide aseptic moulds (different sizes) under aseptic conditions (ISO 5)
7
Lyophilisation
Filling
Packing
Step 5

Lyophilisation – at least 20 hours

withdrawl of liquidity but up-keeping the volume of the filled mass

formation of a porous collagen sponge
Step 6

sealing of the moulds under aseptic conditions (ISO 5)

punching and labeling
8
Step 7

final packet

ready for delivery
2.2.
Criteria for inclusion of Suprasorb® C in Part IX
Suprasorb® C is a Collagen Wound Dressing for lightly to moderately exuding
wounds. It stimulates the healing process in stagnating wounds in all phases of
healing and its open-pore structure removes exudate, as well as other factors that
may inhibit the healing process. Suprasorb C® fulfils the criteria for listing in Part IX of
the Drug Tariff:

It has a CE marking, certifying that it is safe and of good quality, and is
designated as a Class lII device

Suprasorb® C is appropriate for GP and nurse prescribing. It can be used in a
community setting, including long term residential or nursing care, as well as in
a hospital setting. Suprasorb® C can also be used by district nurses as they
perform routine dressing changes without specialist help.

As this paper outlines, Suprasorb® C is cost-effective in comparison with the
existing treatment regimens in community care and offers ease of use and
savings in time, materials and resources.
It is proposed to include Suprasorb C in the Drug Tariff Part IX a in the section:
Wound Management Dressings, Protease Modulating Matrix – Sterile.
3. Indications for the use of Suprasorb® C
It is expected that Suprasorb® C will be predominantly used in chronic leg ulcers,
pressure ulcers and diabetic foot ulcers. These three indications annually add up to
650.000 wounds (Thomas 2006).
9
3.1.
Venous leg ulcers
Chronic venous diseases such as varicosities, post-thrombotic syndrome and chronic
venous insufficiency are among the most common diseases in western countries.
The majority of leg ulcers are caused by problems in the veins, resulting in an
accumulation of blood in the legs. The prevalence of venous ulceration is rising with
the increasing age of the population. About one percent of people in western
countries will suffer from a leg ulcer at some time. A study among 252.000 people in
London found 113 ulcerations - a prevalence of 0.04 per cent (Moffat et al. 2004).
Venous ulceration represents the most prevalent form of hard-to-heal wounds and
these problematic wounds have a significant impact on total healthcare costs.
Demographic factors, including an ageing population and a rising number of obese
people, are leading to a growing population of patients with associated problems
such as venous, lymphatic and diabetic problems. This underlines the impact of
venous ulcers on healthcare costs. Most of the clinical management of chronic leg
ulcers falls to primary care. Over 80% of chronic ulcers are cared for in the
community, although some patients will be treated in hospital. Healing rates in the
community are low. It is known that recurrence rates are certainly in excess of 67%
and may be much higher.
3.2.
Pressure ulcers
Pressure ulcers are lesions of the skin and tissue that result from a period of
pressure, often arising in immobile patients. Excessive pressure in the tissue results
in a restriction of the flow of oxygen and nutrients which can result in necrosis of the
tissue and loss of skin. Approximately 412,000 individuals develop a new pressure
ulcer annually in the UK, at a cost to the healthcare system of at least £180–321
million per annum. Pressure ulcers with the accompanying loss of local circulation
are further prone to the accumulation of devitalized necrotic tissue, which additionally
reduces the possibility of nutrients reaching the wound and damages new epithelial
and granulation cells.
10
3.3.
Diabetic foot ulcers
The prevalence of foot ulcers is about 6% in the diabetic population which add up to
84.000 ulcers per year (Gordois et al. 1996). Diabetic foot ulcers require an
integrated, multidisciplinary management programme that treats the whole patient
and combines effective wound care with pressure offloading and diabetic control.
They present a unique challenge as the impact of diabetes extends beyond
glycaemic control, affecting protein synthesis, white cell function, oxygen
transportation and utilisation and growth factor availability. These complications are
compounded by poor glycaemic control and peripheral vascular disease.
11
4. Clinical evidence for Suprasorb® C
Collagen dressings
Collagen dressings have been applied to chronic stagnating wounds for decades
(Andriessen et al. 2009a, Boateng et al. 2008, Abel et al. 2004, Schönfelder et al.
2004b, Schönfelder et al. 2004c, Metzmacher et al. 2004a, Metzmacher et al. 2004b,
Boom et al. 2004, Polignano et al. 2004, Eberlein et al. 2003, Vin et al. 2002, Veves
et al. 2002, Morgan 2002). These dressings stimulate wound healing by binding free
radicals, including free iron and zinc (Vin et al. 2002, Veves et al. 2002). Most
collagen used clinically has been type I collagen, isolated from animal sources,
including cow, pig and horse hides, bones and tendons. The abundance and relative
ease of isolation has made type I bovine collagen an attractive and economical
source of bulk material. The bovine collagen dressing is more beneficial than
collagen dressings from other sources and is safe to use, as absorbed collagen is
quickly degraded by collagenase during the wound healing process. Other collagen
products, such as oxidised celluloses or gelatin (hydrolysed collagen), take much
longer to be degraded (Table 6), (Andriessen 2003). In modern wound management,
collagen dressings are used as beneficial covers for chronic wounds, because of
their ability to keep the wound climate moist. Because of its porous structure and as
the result of capillary activity, collagen can absorb large quantities of fluid (Landsman
et al. 2009, White et. al. 2009, Wilson et al. 2008, Rolstad et al. 2007, Dissemond
2006, Ovington et al. 2005, Krasner 1997).
Reviews
O'Donnell et al. 2006 discussed whether more "modern" complex wound dressings
can improve the healing of venous ulcers to a greater extent than simple wound
dressings. They conducted a systematic review of randomized controlled trials
(RCTs) of wound dressing trials published from 1997-2005. They concluded that
specific wound dressings can improve both the proportion of ulcers healed and the
healing time more than only adequate compression and a simple wound dressing.
The selection of a specific dressing, however, will depend on the ease of application
of the dressing, patient comfort, wound drainage absorption, and expense (O'Donnell
et al. 2006). Sweitzer et al. 2006 stated that the current treatment in diabetic topical
wound management includes debridement, topical antibiotics, and a state-of-the-art
12
topical dressing. State-of-the-art dressings are a multi-layer system that can include a
collagen cellulose substrate, neonatal foreskin fibroblasts, growth factor containing
cream, and a silicone sheet covering for moisture control. (Sweitzer et al. 2006)
Rudnick 2006 considered that using collagen dressings can play a vital role in wound
healing and should be considered as an alternative to more expensive dressings
(Rudnick 2006).
State of the Art
Collagen dressings plays a major role in wound healing (Sweitzer et al. 2006,
Rudnick et al. 2006, King et al. 2006, Purna et al. 2000). These dressings have
demonstrated their efficacy in the treatment of secondary healing of wounds such as
pressure ulcers, venous ulcers and diabetic ulcers and second-degree burns (King et
al. 2006). The knowledge of the cell biology of wound healing now allows the rational
design of wound management products that stimulate healing of compromised
wounds, such as diabetic ulcers and venous leg ulcers. Collagen dressings represent
a new generation of bioactive therapies that interact with various phases of the
healing process and enhance the ability to treat compromised wounds (Moore 2003).
The clinical findings in wound healing for collagen dressings show advantages in
comparison to standard dressings. In a randomised controlled study on patients with
venous leg ulcers, Vin et al. 2002 found faster healing rates after with collagen than
with non-adherent dressing, although the results were not significant (Vin et al. 2002).
Still et al. 2003 demonstrated that a collagen dressing was significantly more
effective in facilitating timely wound closure of split-thickness skin donor sites than a
standard dressing (Still et al. 2003). However, Rennekampff et al. 2006 found only
minor differences in donor sites wounds after the application of either gauze,
biosynthetic wound dressing, an occlusive film dressing or a collagen foil
(Rennekampff et al. 2006). In a randomised, controlled trial with patients with diabetic
foot ulcer, Veves et al. 2002 found borderline significance in the improvement in
healing time in patients with wounds of less than 6 months' duration after use of the
collagen dressing (control: moistened gauze), (Veves et al. 2002).
When compared to other moist wound healing dressings Suprasorb ® C has
demonstrated significant advantages (Eberlein et al. 2000, Eberlein et al. 2003,
Boom et al. 2004, Beckert 2006, Wild et al. 2007). Collagen exhibits high in vitro
13
binding capacity for different inflammatory mediators, like proteases and cytokines.
Collagen of various origins exhibits different binding capacity for IL-1ß and TNF-α;
bovine collagen performed best in the binding assays (Wiegand et al. 2008a).
Moreover, bovine collagen has considerable binding capacity for growth factors and
for neutrophil elastase (Wiegand et al. 2008b,c). The working group Andriessen and
Polignano looked at granulating venous leg ulcers characterised by low tcPO2. The
study evaluates and compares the effect on microcirculation in leg ulcers of
application of a foam dressing, a collagen dressing and paraffin gauze. For
compression therapy, a short stretch bandage system with foam under padding was
used (Andriessen et al. 2009a, Wiegand et al. 2010, Polignano et al 2004).
In vitro studies
Schönfelder et al. 2004 investigated the binding capacity of Suprasorb® C for
inflammatory cytokines. The results showed the ability of Suprasorb ® C to bind the
inflammatory cytokines IL-1ß and IL-6 (Schönfelder et al. 2004a). Non-healing
chronic wounds, e.g. diabetic or venous ulcers, contain elevated levels of proteases,
such as elastase from polymorphonuclear granulocytes (PMN elastase). The
overproduction of proteolytic enzymes leads to considerably reduced concentrations
of growth factors and proteinase inhibitors, resulting in an imbalance between
degradation and remodeling processes. Therefore the reduction in PMN elastase
within the wound fluid seems to be a suitable way to support the normal wound
healing process (Wiegand et al. 2010, Schönfelder et al. 2004b). Schönfelder et al.
2004b looked at the ability of Suprasorb® C to bind PMN elastase, both from a
defined elastase solution and from wound fluid. Suprasorb ® C reduced the
concentration of residual PMN elastase in a time depended manner. After 4 hours,
this reduction was statistically significant (p < 0.01), (Schönfelder et al. 2004b). Nonhealing wounds exhibit a lack of essential growth factors, e.g. the platelet derived
growth factor (PDGF) and the coagulation factor XIII. This is due to increased
proteolytic degradation by proteases. Because of the imbalance between
degradation and remodelling processes, chronic wounds persist in the inflammatory
phase of the normal healing process and often remain nonhealing for months or even
years. It was shown that topical application of factor XIII could accelerate the healing
rate of venous leg ulcers. In order to support the normal wound healing process, an
efficient protection of growth factors, especially of factor XIII, is required. Schönfelder
14
et al. 2004c investigated the ability of Suprasorb® C to protect PDGF-BB and factor
XIII from proteolytic degradation. Suprasorb® C is able to bind growth factors.
Compared to reference and control samples, after 30 minutes of incubation, a
significant (p<0,05) decrease of the PDGF-BB concentration could be found out.
PDGF-BB could completely be recovered from Suprasorb® C. In the presence of
plasmin, a characteristic component of chronic wound fluids, the elution rate was only
about 10 percent. However, the ORC/collagen dressing did not release PDGF-BB in
the presence of plasmin. Additionally, Suprasorb® C binds significant quantities of
factor XIII, which can be recovered. The authors concluded that Suprasorb® C
absorbs not only fluids, but can also bind the platelet-derived growth factor BB as
well as the coagulation factor XIII and releases them successively into the wound
fluid. Due to the binding, PDGF-BB was partly protected from proteolytic degradation.
Despite the result that factor XIII was not degraded by plasmin, we assume that
factor XIII could also be protected from destruction by other proteases.
Consequently, the binding of growth factors would retain them in the wound fluid. So
it could so be beneficial in wound healing disorders (Schönfelder et al. 2004c).
Collagen binds PDGF-BB at different rates, depending on its origin. Wiegand et al.
2008b explored the PDGF-BB binding capacity of different collagen wound dressings
(bovine, porcine, and equine collagen). Bovine collagen has considerable binding
capacity for this growth factor. During binding, PDGF-BB is not only protected from
proteolytic degradation, but preserves its biological activity as well. Porcine and
equine collagen showed less binding affinity for PDGF-BB (Wiegand et al. 2008b).
Despite the finding that factor XIII is not degraded by plasmin, it is assumed that
factor XIII can also be protected from destruction by other proteases. Consequently,
binding of growth factors would retain them in the wound fluid, suggesting that they
are beneficial in treating wound healing disorders (Wiegand et al. 2008b).
Metzmacher et al. 2004a studied Suprasorb® C, in an attempt to characterize the
carrier system, its swelling behaviour and the degradation by bacterial collagenase.
The influence of chemical cross-linking with ethyl-dimethylaminopropylcarbodiimide
(EDC) on these parameters was analysed. The authors concluded that minirods of
insoluble collagen are a promising drug delivery system. Two features important for
the drug release, swelling and degradation, can be controlled by cross-linking. Both
the time of matrix disintegration in buffer and the in vitro degradation by bacterial
15
collagenase are delayed at higher degrees of EDC cross-linking. Consequently, the
properties of this matrix can be adapted depending on the drug and the desired
release profile (Metzmacher et al. 2004a). Metzmacher et al. 2004/2007 studied
Suprasorb® C's role in binding MMPs to collagen material. Gelatinase A (MMP-2) and
gelatinase
B
(MMP-9)
were
investigated,
because
of
their
important
pathophysiological role in chronic wounds. The conversion of chronic and nonhealing wounds into healing wounds is associated with a reduction in elevated MMP2 and MMP-9 activities. In vitro, Suprasorb® C containing collagen type I can reduce
the levels of these two MMPs. The reduction in the MMP-9 levels is significant. It is
suggested that wound treatment with this dressing is useful to correct the imbalance
of MMP levels in chronic wounds (Metzmacher et al. 2004b, Metzmacher et al. 2007).
Nissen et al. 2003 examined the anti-oxidative potential of Suprasorb® C in chronic
poorly healing wounds. They demonstrated that free radicals and metal ions could be
removed from the wound (Nissen et al. 2003). The dressing was absorbent and
debris was removed from the wound bed. In addition, inflammation was reduced,
thus supporting wound healing (Nissen et al. 2003, Abel et al. 2004, Schönfelder et
al. 2004b, Schönfelder et al. 2004c). Matrix metalloproteinases (MMP) and their
physiological inhibitors, the tissue inhibitors of metalloproteinases (TIMPs), play also
significant roles in angiogenesis and therefore as well in wound repair. Piatkowski et
al. 2005 and 2006 evaluated the concentration and expression of MMP-2, MMP-9,
TIMP-1 and TIMP-2 and activity of gelatinase, plasmin, and elastase in wound fluid of
patients with pressure sores. The combination of Suprasorb® C and Suprasorb® P
(polyurethane foam dressing) showed a decreasing gelatinase activity over the time
compared to Suprasorb® P only. Wound fluids from patients of Suprasorb® C and
Suprasorb® P had a more effect on angiogenesis than wound fluids from Suprasorb®
P only. The working group pointed out that faster wound closure was achieved with
the combination of Suprasorb® C and Suprasorb® P (Piatkowski et al. 2006,
Piatkowski et al. 2005). Wiegand et al. 2008c investigated the influence of different
collagen wound dressings (bovine, porcine, and equine collagen) on elastase
concentration, as well as the amounts of MMP-2 and MMP-13. Collagen exhibited
significant binding capacity for all proteases tested. Bovine and equine collagen type
I significantly reduced the concentration of neutrophil elastase, even after incubation
for only 1 h. However, the binding affinity of porcine collagen for elastase was much
16
lower. Bovine, porcine and equine collagen also had different affinities for MMP-2,
whereas their binding to MMP-13 was similar (Wiegand et al. 2008c, Wiegand et al.
2010).
In vivo studies
Andriessen et al. 2009a compared the effect on the microcirculation in venous leg
ulcers of different treatment regimens that promote a moist wound environment.
Twelve patients with non-healing venous leg ulcers were randomised to receive
either a foam dressing (Suprasorb® P), a collagen dressing (Suprasorb® C) plus the
foam dressing, or paraffin gauze (control). All patients wore short-stretch high
compression bandages. Parameters used to measure the effects of the treatments
on the microcirculation were: TcPO2 measurements, video laser Doppler
measurements and the number of capillaries in the wound bed. The progression
towards healing was measured by the reduction in ulcer area and formation of
granulation tissue. The treatment period was four weeks. Significant increases in
TcPO2 values were reported between baseline and week 4 for patients receiving the
foam dressing only or the collagen plus foam dressing combination (p<0.008 versus
p<0.003, respectively). There was also a significant increase in the number of
capillaries for the collagen plus foam treatment only (p<0.002), (Andriessen et al.
2009a, Wiegand et al. 2010, Polignano et al. 2004 (poster)). A clinical pathway was
developed and implemented to improve treatment outcomes for patients with venous
leg ulcers. The pathway and medical devices (Rosidal® sys, Suprasorb® A,
Suprasorb® P, and Suprasorb® C, Lohmann & Rauscher GmbH, Rengsdorf,
Germany) were tested by case evaluation. Patients with venous leg ulceration (n=20)
were recruited to the clinical evaluation. Examination was performed upon
presentation, and then at 2-week intervals for 12 weeks. The patients were then
followed until ulcer closure. The outcome of the study group (SG) was compared to
the results of a randomly selected patient control group (CG) at the centre before
implementing the clinical pathway. After implementation, a statistically significant (P <
0.005) shorter period for ulcer closure was demonstrated for the SG when compared
to previous treatment given to the CG. In the SG, 5/10 ulcers closed within 12 weeks
versus 3/10 in the CG. An improvement in QOL was noted for the SG (P < 0.05 for
the combined parameters, and P < 0.005 for pain), as well as cost savings (P < 0.05).
17
The CP applied throughout the complete care chain improved quality of treatment
outcomes and made effective use of resources and materials (Andriessen et al.
2009b). In a trauma setting, Gourdazi et al.1992 treated 34 patients with Suprasorb ®
C from 1987 to 1990. Eleven patients had soft tissue defects, ten had complex open
fractures, seven patients had infected soft tissue wounds and six deep full-thickness
burns. In all cases, the wound bed was granulated and vascularised after 6-8 days
of collagen dressing, covering the defects with a skin graft. The dressing influenced
the bacterial environment of the wound and actively supported the wound healing
process. No biological incompatibility to the collagen dressing material was observed
(Gourdazi et al.1992). Eberlein et al. 2003 examined the use of Suprasorb ® G ( a
hydrogel dressing), C and P for chronic poorly healing wounds and concluded that
the system was beneficial for the management of leg ulcers of different aetiologies
and diabetic foot ulcers. Especially Suprasorb® C performed very well when a semiocclusive dressing was applied as a secondary dressing (Eberlein et al. 2003). A
study by the same group looking at the efficacy of Suprasorb ® C when applied on
chronically poorly healing wounds (n=35) and demonstrated an improvement in
wound status in 71% of the cases. These wounds had not improved within 44.6
months (mean) prior to study recruitment (Eberlein et al. 2000). Boom et al. 2004
evaluated the clinical use of Suprasorb® C in 10 patients with extensive non-healing
surgical wounds. This prospective descriptive clinical study used a questionnaire
design to document treatment details and outcomes. Patients had been previously
treated with other dressings, such as honey and silver dressings. The authors
concluded that Suprasorb® C is effective, well tolerated and user-friendly when used
for secondary healing of complex surgical wounds (Boom et al. 2004). Adequate
oxygen supply plays an important role in the wound healing process. Ischaemic
wounds heal poorly. Angiogenesis and therefore proliferation of healthy granulation
tissue are slow. Beckert and Coerper 2006 investigated whether Suprasorb® C is
capable of enhancing angiogenesis in the wound. 20 consecutive patients treated
with Suprasorb® C were included into the study. The O2C probe was used to assess
relative blood flow (flow), flow velocity (velo), as well as relative hemoglobin
concentration (rHb) and venous hemoglobin oxygenation (SO2) directly at the wound
site in 2 and 6 mm wound depth (mean + SEM). The measurement was performed in
weekly intervals for 8 weeks. There were 8 patients with ischemic wounds and 12
18
patients with venous ulcers enrolled. In 2mm wound depth, there was a significant
lower velocity (p=0.004), relative hemoglobin concentration (p=0.047) and venous
hemoglobin oxygenation (p=0.017) in ischemic wounds compared to venous ulcers.
However, the relative blood flow was not different (p=0.198). During treatment with
Suprasorb® C all parameters increased over a period of 8 weeks, demonstrating a
trend towards an increased relative blood flow after treatment with Suprasorb® C.
Beckert and Coerper concluded that the treatment with Suprasorb® C lead to an
increase of blood flow and hemoglobin parameters in all wounds but this increase did
not reach statistical significance (Beckert et al. 2006). Wild et al. 2007 included 8
patients with therapy refractory leg ulcer in an observational study. The patients
received collagen foam therapy for 22.6 days. The initial size of the leg ulcers was
923 mm². At the end of the observation period, the wound size was reduced to
504.64 mm² (54.67%) due to epithelialisation. The authors concluded that collagen
dressings play an important role for starting epithelialisation and can be used in
cases when skin transplantation is impossible (Wild et al. 2007).
Efficacy of a collagen dressing applied in fifty patients with stagnating wounds
of various etiologies (Andriessen, van den Wijngaard 2012)
The aim of the study was to evaluate the pratical use of a native collagen type I
dresssing for n= 50 stagnating wounds of various etiologies. Collagen based wound
dressings have been shown to reduce MMP-2 and MMP-9 levels helping to restore
the physiological balance between MMP´s and TIMP´s (1,2) thus kickstarting the
stagnating wound healing process.
Methods
All the patients which were included in the study had given agreement and no ethical
committee aproval was requiered due to the colllagen product was already used in
the clinics.
Patients at the 5 study centers had stagnating wounds that were free of necrotic
tissue and/or slough and clinical signs of infection. The ulcers did not respond to
previous standard treatment, which comprised debridement, moist wound healing
dressings, NPWT and preventive measures. Case ascertainment was used looking at
time to healing, starter function of the collagen dressing, Suprasorb C, (shift from
19
inflammation to granulation), patient reported pain measured before dressing
changes (VAS, 10 point scale) and handling of the dressing regime. Wound healing
was assessed using a clinical observation scale and digital photographs, comparing
day 0 versus day 14 results. Patients were then followed until wound closure.
Patients were treated in both an in and out-patient setting at the five participating
centers. Dressing changes were on average twice weekly and took place at the
discretion of the clinician depending on exudate production. Wounds were cleansed
with saline using the wet to dry phase system. A foam dressing, Suprasorb P, or an
alginate, Suprasorb A, was used as a secondary dressing to cover the collagen
dressing. Patients received the collagen dressing for a maximum of 14 days, after
which the dressing was discontinued and foam used as a primary dressing. Patients
received standard preventive and treatment measures in line with the aetiology and
local guidelines, such as compression for venous leg ulcers and off-loading for
diabetic foot ulcers.
Results
Fifty cases (n = 36 females and n = 14 males) were included, n=10 large stagnating
surgical wounds, n=20 diabetic foot ulcers and n=20 wounds of various etiologies,
such as pressure ulcers and venous leg ulcers. The patients had a mean age of 58
years (SD ±1.32; range 36 – 84) (Table 1). Depending on the exudate production,
either a foam dressing or an absorbent pad was used as a secondary dressing. In all
observed cases (N=50/50 (100%) the wound bed condition improved within 14 days
of treatment, indicating a fast reduction of inflammation. The dressing was
comfortable and easy to handle. The mean treatment time for the surgical wounds
was 68.6 days (±SD 0.64) and the wound area reduction was 97.3%. For the diabetic
foot ulcers this was 76.4 days (±SD 1.34) with a 100% area reduction and for the
venous leg ulcers this was 71 days (±SD 0.34). Two typical cases are presented to
illustrate the results.
20
Patient’s characteristics
Case 1
The 64 year-old male has diabetes mellitus type II since 1998. Additional pathologies
were retinopathy and severe neuropathy. Due to poor concordance his blood glucose
levels were difficult to control, moreover he had no awareness of low blood glucose
values. Laboratory tests: HbA1c 10% = 86 mmol/mol. He receives insulin 4/day. Due
to many recurrences he was treated by the vascular surgeon and the rehabilitation
outpatient department. Despite 6 months of treatment with contact casting the ulcer
failed to close. He was then referred to the Diabetes Specialist Nurse. Wound
treatment comprised Suprasorb C covered with a secondary dressing. Offloading
with felt, as the patient refused to wear floss shoes. Removal of callus was performed
weekly in the first 4 weeks, followed by once/2 weeks for 3 months. As a result of this
intensive therapy the ulcer had closed in 9 weeks. After ulcer closure he was referred
to an orthopedic shoemaker for customized orthopedic shoes. He now visits the clinic
regularly to prevent ulcer recurrence and to repeat education regarding foot care and
blood glucose values control (Fig 1a – Fig 1e).
21
Case 2
The 76-year-old woman had chronic venous hypertension. She smoked about 20
cigarettes/day. After debridement the venous ulcer was covered with the collagen
and a foam was used as a secondary dressing. She received compression with a
tubular compression system. After 2 weeks the stagnating wound started to show
signs of healing. Complete wound healing was achieved in 9 weeks (Fig 2a – Fig 2c).
Conclusion

The stagnating wounds that were treated with the collagen dressing moved
towards epithelialization.

In daily practice the use of the collagen dressing was shown to be easy,
improving clinical outcomes, patient comfort and reducing pain.

Moreover the collagen dressing helped kickstarting the stagnating wound
healing process.
22
5. Cost implications of Suprasorb® C
The aim of this economic evaluation is to assess the costs and cost-effectiveness of
Suprasorb® C in the treatment of chronic wounds compared to current treatments
from the perspective of the National Health Service. Main assumptions on material or
personnel costs have been derived from an NHS guidance (Leaper et al. 2008). Due
to the perspective taken, societal or indirect costs (such as the value of lost work
time) could not be included in the analysis. However, the exclusion of lost productivity
is unlikely to have a significant effect on the results, since most of patients with
chronic wounds are over 60 years of age.
The cost-effective treatment of a chronic wound depends on the total labor and
materials cost entailed from treatment initiation until treatment endpoint is attained.
There is currently little evidence on the impact of different wound dressings on the
healing time. The main advantages of advanced wound care products include the
potential to improve healing rates, reduction of symptoms, improvements of quality of
life and reduction in healthcare costs due to lesser dressing changes.
In an NHS guidance for surgical site infection (Leaper et al. 2008) a costing analysis
was conducted. The costs shown below included the cost of the dressing (10 cm ×
10 cm) and a nurse´s time to change a dressing. It was assumed that each dressing
change would require 10 minutes of a nurse´s time, with a cost per hour for a nurse
of ￡22. For comparison, 10 cm by 10 cm wound dressings were used or the next
available size above (or 15 g for hydrogel dressings). This dressing size was chosen
because it allowed inclusion of the majority of brands (Leaper et al. 2008).
Dressing type
Frequency of change
Mean cost/week
Alginate
2–3 days
￡16.32
Topical Antimicrobials
2–3 days
￡25.22
Foam
3–4 days
￡13.57
Hydrogel
1–2 days
￡38.87
Hydrocolloid
1–2 days
￡33.46
Protease-modulating matrix
4–7 days
￡11.77
Costing analysis of a 10 cm × 10 cm dressing by dressing type: Own representation based on Leaper
et al. 2008
23
A suggested range for number of changes that would be required for each dressing
type was decided by expert opinion (Leaper et al. 2008). As this cost-minimisationanalysis shows Protease-modulating matrix like Suprasorb® C have a cost advantage
if compared to other dressing types. This advantage derives from the lower frequency
of dressing changes required for Protease modulating matrix.
The main conclusion of the NHS guidance for surgical site infection was that it is
important to take into account the additional costs of changing dressings as well as
the initial price of each dressing when choosing which dressings to use.
6. Summary
Suprasorb® C meets all the requirements of listing in Part IX of the Drug Tariff. It has
a CE marking, certifying that it is safe and of good quality, and is designated as a
Class lII device.
It is appropriate for GP and nurse prescribing and it will be primarily used in a
community setting. The three-phase effect of Suprasorb® C affords a high degree of
treatment safety – by cleansing the wound and changing the wound environment in
the exudation phase, by stimulating the granulation tissue in the granulation phase,
and by accelerating the process of re-ephitelisation in the epithelisation phase.
At the proposed price Suprasorb® C is cost-effective if compared to other dressing
types and comparable to a Collagen/Oxidized Regenerated Cellulose Dressing
(Promogran®, Systagenix Wound Management, Gargrave, UK).
24
7. Reference List
Abel M, Nissen HP, Ruth P. Beta and gamma radiated collagen and native
Suprasorb® C, their antioxidative properties and potential for chronic wounds. Poster
presentation at the 2nd World Union of Wound Healing Society Meeting, Paris/France,
8-13 July, 2004
Andriessen A, Polignano R, Abel M. Monitoring the microcirculation to evaluate
dressing performance in patients with venous leg ulcers. J Wound Care. 2009a;
18(4): 145-50
Andriessen A, Polignano R, Abel M. Development and implementation of a clinical
pathway to improve venous leg ulcer treatment. Wounds 2009b; 21(5): 127-133
Andriessen A, Huid en wondverzorging in: Leerboek intensive-care-verpleegkunde.
Van den Brink GTWJ, Lindsen F, Uffink Th (eds).Lemma BV Utrecht: 2003; 4.
Edition, Part 2, 25-105
Andriessen A, van den Wijngaard RN. Efficacy of a collagen dressing applied in fifty
patients with stagnating wounds of various etiologies. Poster presentation at the 22nd
European Wound Management Association conference, Vienna/Austria, 23-25th May
2012
Barrett SA, Moore K. Use of Promogran to treat venous leg ulcers. J Wound Care.
2004; 13(1): S2-7
Beckert S, Deutschle G, et al. Increase of angiogenesis in chronic wounds after
application native collagen. European Wound Management Association (EWMA).
Prag/CZ, 18.-20. Mai 2006
Boateng JS, Matthews KH, et al. Wound healing dressings and drug delivery
systems: a review. J Pharm Sci. 2008; 97(8): 2892-923
25
Boom M, Vijverberg A, Vijverberg L. The successful use of Suprasorb C, a collagen
wound dressing, on ten patients with mainly severe surgical wounds. Poster
presentation at the 2nd World Union of Wound Healing Society Meeting,
Paris/France, 8-13 July, 2004
Directive 93/42/EEC of 14 June 1993 concerning medical devices (MDD), OJL 169,
actual Version
Directive 2007/2006/EC of 22 December 2006 (implementing Regulation (EC) No
1774/2002 of the European Parliament and of the Council as regards the importation
and transit of certain intermediate products derived from Category 3 material
intended for technical uses in medical devices, in vitro diagnostics and laboratory
reagents and amending that Regulation)
Directive 1774/2002/EC of 3 October 2002 (laying down health rules concerning
animal byproducts not intended for human consumption); Official Journal L 273,
10.10.2002
Dissemond J. Modern wound dressings for the therapy of chronic wounds. Hautarzt.
2006; 57(10): 881-7
Eberlein T, Kammerlander G, Abel M. Eine neue Kombinationsmöglichkeit für die
Therapie chronisch-stagnierender Wunden. Oral presentation at the DGFW;
Augsburg, Germany 2003
Eberlein T, Kammerlander G. Suprasorb C – Anwendungsbericht. Suprasorb® C in
der modernen feuchten Wundbehandlung, 2000
Goudarzi YNI, Khodadayan C, Hertel P. Klinische Erfahrungen mit einem
kollagenhaltigen
Wundverband
bei
schweren
Weichteilverletzungen. Ak Traumatol 1992; 22: 183-242
26
traumatisch
bedingten
Hollister C, Li VW. Using angiogenesis in chronic wound care with becaplermin and
oxidized regenerated cellulose/collagen. Nurs Clin North Am. 2007; 42(3): 457-65
Instruction for use Suprasorb C. Lohmann & Rauscher GmbH & Co. KG. 2010-01-14
(European market)
ISO 10993-1:2010, Biological Evaluation of Medical Devices – Part 1: Evaluation and
testing Jochims K. Preclinical evaluation Suprasorb C. PB-31-00021-01. 2010-02-26
King S. Catrix: an easy-to-use collagen treatment for wound healing. Br J Community
Nurs. 2005; 10(9): S31-4
Krasner, D. Dressing decisions for the twenty-first century: on the cusp og a
paradigm shift. In: Krasner, D. Chronic wound care - a clinical source book for
healthcare professionals. Ausgabe 3. ed., Wayne, Pa: Health Management Publ.
2001: 311-319
Landsman A, Taft D, Riemer K. The role of collagen bioscaffolds, foamed collagen,
and living skin equivalents in wound healing. Clin Podiatr Med Surg. 2009; 26(4):
525-33
Leaper, D et al. (2008). Prevention and treatment of surgical site infection: summary
of NICE guidance. BMJ; 337: a1924.
Metzmacher I, Ruth P, et al. Swelling and degradation of collagen minirods. Poster
presentation at the 2nd World Union of Wound Healing Society Meeting,
Paris/France, 8-13 July, 2004a
Metzmacher I, Ruth P, et al. Inactivation of MMP-2 and MMP-9 by Suprasorb C.
Poster presentation at the 2nd World Union of Wound Healing Society Meeting,
Paris/France, 8-13 July, 2004b
27
Metzmacher I, Ruth P, et al. In vitro binding of matrix metalloproteinase-2 (MMP-2),
MMP-9, and bacterial collagenase on collagenous wound dressings. Wound Repair
Regen 2007; 15(4): 549-55
Morgan G. Wounds - What should a dressings formulary include? Hospital
Pharmacist 2002; 9: 261-266 Moore K. Compromised wound healing: a scientific
approach to treatment. Br J Community Nurs. 2003; 8(6): 274-8
Nissen HP, Abel M. Das antioxidative Potential von Suprasorb C – positiver Einfluss
bei chronisch-stagnierenden Wunden. Poster 7th year congress DGFW; Augsburg,
Germany, 2003, 26-27/06.
O'Donnell TF Jr, Lau J. A systematic review of randomized controlled trials of wound
dressings for chronic venous ulcer. J Vasc Surg. 2006; 44(5): 1118-25
Ovington LG, Eisenbud D. Dressings and cleansing agents. In: Morison M. Chronic
woundcare - a problem-based learning approach. Edinburgh (e.g.), Mosby 2005:
117-128
Piatkowski A, Ulrich D, Abel M, Pallua N. Suprasorb P and Suprasorb C have
influence on angiogenesis and matrix metalloproteinases in pressure sores.
Conférence des Plaies et Cicatrisations (CPC), Paris 14.-16. Jan. 2007
Piatkowski A, Ulrich D, Abel M, Pallua N. The influence of Suprasorb® C and
Suprasorb® P on angiogenesis and matrix metalloproteinases in pressure sores.
Annual Congress 2006 of the ETRS 13.09.-16.09.2006, Pisa/Italy
Polignano R, Andriessen A, Abel M. The effect of MWH dressings on microcirculation
in leg ulcers a pilot study. Oral presentation at the 2nd World Union of Wound
Healing Society Meeting, Paris/France, 8-13 July, 2004
Rangaraj A, Harding K, Leaper (2011). Role of collagen in wound management.
Wounds UK 7(11): 54-63.
28
Rennekampff HO, Rabbels J, et al. Comparing the Vancouver Scar Scale with the
cutometer in the assessment of donor site wounds treated with various dressings in a
randomized trial. J Burn Care Res. 2006; 27(3): 345-51
Rolstad BS, Ovington LG. Principles of wound management. In: Bryant RA, Nix DP.
Acute and chronic wounds - current management concepts. St. Luois, Montana,
Mosby Elsevier 2007: 391-426
Rudnick A. Advances in tissue engineering and use of type 1 bovine collagen
particles in wound bed preparation. J Wound Care. 2006; 15(9): 402-4
Schönfelder U, Abel M, et al. Das Bindungsvermögen von Suprasorb C für
entzündungsfördernde Zytokine. Poster presentation at the 8. Annual Congress of
the German Society for Wound healing and Wound treatment, Weimar 23.24.09.2004a
Schönfelder U, Abel M, et al. Chronic wounds influenced by the collagen wound
dressing Suprasorb C, effect on PNM elastase. Poster presentation at the 2nd World
Union of Wound Healing Society Meeting, Paris/France, 8-13 July, 2004b
Schönfelder U, Abel M, et al. Chronic wounds influenced by the collagen wound
dressing Suprasorb C, effect on platelet derived growth factor and coagulation factor
XIII. Poster presentation at the 2nd World Union of Wound Healing Society Meeting,
Paris/France, 8-13 July, 2004c
Sweitzer SM, Fann SA, et al. What is the future of diabetic wound care? Diabetes
Educ. 2006; 32(2): 197-210
Vasel-Biergans A, Probst W. Wundauflagen für die Kitteltasche. Wissenschaftliche
Verlagsgesellschaft mbH Stuttgart, 2003. 225-48
Veves A, Sheehan P, Pham HT. A randomized, controlled trial of Promogran (a
29
collagen/oxidized regenerated cellulose dressing) vs standard treatment in the
management of diabetic foot ulcers. Arch Surgery 2002; 137: 822-827
Vin F, et al. Healing Properties of Promogran in Venous Leg Ulcers: Results of a
Randomised Controlled Study. J Wound Care 2002; 11: 335-41
White R, McIntosh C. A review of the literature on topical therapies for diabetic foot
ulcers. Part 2: Advanced treatments. J Wound Care. 2009; 18(8): 335-41
Wiegand C, Schönfelder U, Abel M, Ruth P, Kaatz M, Hipler UC. Protease and
proinflammatory cytokine concentrations are elevated in chronic compared to acute
wounds and can be modulated by collagen type I in vitro. Arch Dermatol Res. 2010;
302(6): 419-28
Wiegand C, Abel M, et al. Effect of the sterilization method on the performance of
collagen type I on chronic wound parameters in vitro. J Biomed Mater Res B Appl
Biomater. 2009; 90(2): 710-9
Wiegand C, Abel M, et al. Comparison of the binding capacity of collagen from
different origin for IL-1ß and TNF-α. Wounds-UK 2008 Wound Care Conference,
Harrogate 10-12th November 2008a
Wiegand C, Abel M, et al. Binding capacity of collagen from different for PDGF-BB.
Wounds- UK 2008 Wound Care Conference, Harrogate 10-12th November 2008b
Wiegand C, Abel M, et al. Influence of the collagen origin on the binding affinity for
inflammatory proteases. Wounds-UK 2008 Wound Care Conference, Harrogate 1012th November 2008c
Wild T, Stremitzer S, et al. Collagen dressing (Suprasorb C) induces epithelisation in
chronic leg ulcers. European Wound Management Association (EWMA), Prag/CZ,
18.-20. Mai 2006
30
Wilson F, Kohm B. Verbandmittel, Krankenpflegeartikel, Medizinprodukte. 8. Auflage,
Stuttgart: Dt. Apotheker-Verlag 2008
Wollina U, Schmidt WD, et al. Some effects of a topical collagen-based matrix on the
microcirculation and wound healing in patients with chronic venous leg ulcers:
preliminary observations. Int J Low Extrem Wounds. 2005; 4(4): 214-24
31