Pharma & Healthcare News November 2010

Pharma & Healthcare News Alsiano No. 13 • November 2010

Contents Maximising yeast’s potential..................................1 Update - EU approval of stevia...................................2 AEROSIL® and SIPERNAT® for free-flowing and noncaking sugars and sugar alcohols....................................3 KLEPTOSE®: multifunctional excipients for molecular encapsulation..........................6 Heavy metals: an overview of European legislation..........8 SEPIFILMTM - the breakthrough in moisture protection................................9 The Alsiano Healthcare team.......................................10

Maximising yeast’s health potential Lesaffre Human Care is presenting a new probiotic yeast for people suffering from intestinal discomfort and Irritable Bowel Syndrome (IBS)

By Robin Wyers Lesaffre Human Care has broadened its range of probiotic yeasts with Lynside Pro GI+, a probiotic yeast intended for people suffering from intestinal discomfort such as that caused by Irritable Bowel Syndrome (IBS).

Lynside Pro GI+ is a Saccharomyces cerevisiae yeast targeted at intestinal discomfort. It was selected by Lesaffre among 6,000 proprietary strains and has been registered with the French National Collection of Microorganism Cultures (CNCM). A patent application covering many different areas has been filed. Furthermore, many preclinical trials and one large clinical trial have been conducted successfully with Lynside Pro GI+, and two other clinical trials will have been carried out by the end of 2011.

A European Article 13.5 functional health claim has been submitted to EFSA, regarding the new probiotic yeast, Lynside Pro GI+. The proposed health claim is: “Noticeably reduces digestive discomfort after 4 weeks of consumption”.

Publisher: Alsiano A/S Circulation: 650 copies Editor-in-chief: Anders Hager Coordinator, text, lay-out: Dorthe Andersson Pharma & Healthcare News is published twice a year and distributed to customers and other interested parties. Reproduction of articles appearing in Pharma & Healthcare News requires prior consent of the author. Alsiano is not responsible for the content of articles written by external authors.

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Scientific support Since 2005, preclinical trials (in-vitro, ex-vivo, in-vivo) have been ongoing with Lynside Pro GI+. These trials have demonstrated that the strain • survives transit through the gastrointestinal tract • has anti-inflammatory properties • reduces the perception of intestinal pain One of the preclinical trials on the anti-inflammatory potential of several non-pathogenic yeast strains was published in the World Journal of Gastroenterology (May 2010).

Two oral presentations were given at the American Digestive Disease Week convention in May 2010. The first presented the results of Lynside Pro GI+ on the modulation of bowel pain in preclinical trials, while the second presented interesting effects of Lynside Pro GI+ on the adhesion of entero-invasive Escherichia. coli in patients with Crohn’s disease.

In 2008, a large placebo-controlled double-blind randomised clinical trial was conducted with an international specialist of ... (continues >>)

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Update – EU approval of stevia Since the positive safety opinion on steviol glycosides from the European Food Safety Authority in April this year, the process seems to continue as planned with approval expected in July 2011

By Thierry Liot, Stevia Development Manager, Seppic The approval of stevia is long awaited, and the potential of this natural high intense sweetener is expected to be significant, especially as consumers are veering away from artificial additives towards ingredients with more natural perceptions.

On 29 September, the conference, Preparing for Stevia Approval, was held in London. The main messages delivered at this conference were the following: •

European approval of stevia extracts (all grades complying with JECFA standards) is expected in July 2011. Furthermore, there should be no delay between the approval by the European Commission and the authorisation to launch products on the market.

>> inflammatory bowel diseases, Professor Pierre Desreumaux of the University of Lille (France). In the clinical trial, 200 volunteers with symptoms of IBS took 500 mg/day of Lynside Pro GI+ (8x109 cfu/g) for 8 weeks. The scientists showed that: •

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Intestinal pain and discomfort are greatly relieved after 4 weeks of taking Lynside Pro GI+ (significant difference between placebo and active product).

Lynside Pro GI+ has favourable effects on bowel disorders caused by IBS (abdominal/intestinal pain and discomfort, bloating, flatulence and constipation).

These clinical results have just been presented by Professor Desreumaux at the United European Gastroenterology Week in Barcelona (October 2010). Publication will follow in 2011.

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The end-products containing these stevia extracts will probably be labelled “contains stevia glycosides”.

The E-number (E 960) will most probably never be used on product labels.

The maximum authorised use levels will probably be lower than the ones currently applying in France (for beverages in particular) - this in order to be consistent with the current ADI and experience gathered from the market.

There are no news regarding a possible approval of unpurified extracts (crushed leaves in particular).

Within the European food and beverage sector, the interest for stevia is increasing as the date of approval is now almost official.

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AEROSIL® and SIPERNAT® for free-flowing and non-caking sugars and sugar alcohols Avoid lumps in sugars and sugar alcohols with AEROSIL® fumed silica and SIPERNAT® precipitated silica products

By Evonik Degussa Nearly everyone has discovered the downsides of hygroscopic carbohydrates. Due to the high number of polar hydroxyl groups in those molecules, they greedily attract moisture from the environment. The concerned agglomerates and hard lumps as a consequence are difficult to process further. To ensure a convenient as well as an efficient handling of sugars without time and resource consuming measures to break agglomerates again, it is important to reduce caking and avoid formation of lumps reliably.

polyols depending on the relative humidity of the atmosphere. In figure 1, it can be seen that fructose tends to take up moisture already at relatively low humidity. It is one of the most hygroscopic carbohydrates, followed by polyols such as sorbitol and xylitol.

The absorbed water builds liquid bridges between the individual particles causing them to agglomerate.

At continued exposure to moisture, some amount of the carbohydrate becomes dissolved in this water and,

when dry again at lower relative humidity, the carbohydrate will recrystallise resulting in solid bridges between the particles which lead to the formation of very hard lumps.

This principle is demonstrated in figure 2. SIPERNAT® precipitated silica and AEROSIL® fumed silica can prevent the formation of these liquid or even solid bridges. The silica absorbs the water film on the surface thereby breaking liquid bridges and avoiding growth of solid bridges. (continues >>)

Figure 1: Water uptake of various sugars and polyols depending on relative humidity in the atmosphere. [Based on 1, 2, 3]

Examples of carbohydrates that benefit from the treatment with SIPERNAT® precipitated silica or AEROSIL® fumed silica • • • • • •

Fructose Glucose Lactose Sucrose Sugar substitutes, e.g. xylitol, sorbitol and other polyols Polysaccharides, such as maltodextrin, polydextrose or even starches

Reasons for carbohydrate agglomeration and prevention As soon as the humidity in the environment reaches a concentration specific to each carbohydrate, they immediately start taking up moisture from the vapour phase. This relative humidity is defined as the water activity of the substance. At which point the carbohydrate commences absorbing water depends, amongst other things, on the chemical nature of the substance, its purity and its particle size. Impurities and smaller particle sizes increase the hygroscopicity, which means that moisture is absorbed already at lower ambient humidity [1]. Figure 1 compares the water content of various sugars and

Figure 2: Model describing caking and cakingavoidance by silica of moist and hygroscopic powders.

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Pharma & Healthcare News >> Additionally, the silica acts as a spacer preventing direct contact between the individual carbohydrate crystals.

Especially very fine powders tend to cake as the small particles come into close contact with each other.

Increasing the distance between the individual particles is important to reduce the attraction forces between those small particles and thus improving the flowability of the fine sugar grades.

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Figure 3: Xylitol (particle size max. 10% >250 µm, initial water content max. 0.5 wt%). Left: untreated Xylitol with flow grade 7. Right: treated with 1 wt% SIPERNAT® 50 S, flow grade 3. Mixing in tumbling-mixer type Turbula 45 rpm for 5 min. After storage at uncontrolled ambient conditions in closed glass bottles for approximately one week

Detailed information on the mode of action of silicon dioxide to improve and ensure powder flowability can be found in the Technical Information 1351 “SIPERNAT® and AEROSIL® as Flow Aid and Anticaking Agent” [4].

Example: caking because of moisture uptake As described in figure 1, xylitol is very hygroscopic; it tends to absorb moisture from the environment very fast.

Even when stored at room temperature and humidity levels well below the water activity of this polyol, it absorbs water and forms large lumps decreasing the flowability.

Defined glass funnels can be used to determine flow properties of powders. The powder that flows out without interruption through a smaller outlet diameter of the funnel has a better flowability. Figure 3 (left side) shows the result of keeping xylitol in a sealed glass bottle at ambient conditions. It is obvious that the material is nearly completely caked and therefore not able to flow through the largest funnel opening. This poor flowability is classified as flow grade 7.

Example: poor flowability because of small particle size Another reason for poor flowability and caking of sugars is the size of the particles. The finer the powder, the worse the flow. In figure 4, a disaccharide with a particle size of approximately 130 µm on average was tested for its caking behaviour during storage at elevated temperature and humidity. With a texture analyser, the

hardness of the caked disaccharide was measured and the ability of various anti-caking aids to reduce this hardness was evaluated. The test shows that a dosage of less than 1 wt% of AEROSIL® or SIPERNAT® products is very efficient in reducing the hardness of the caked material.

Figure 4 summarises the results of the test. (continues >>)

Figure 4: 1-α-glucopyranosyl-1-α-glucopyranosid (mean particle size ~ 130 µm) treated with 1 wt% silica. Mixing conditions: vertical lab mixer (Somakon) for 0.25 or 0.5 minutes at 400 rpm. Storage at 30°C, 40% RHumidity for 4 days. Hardness determines the force necessary to scratch off a certain layer of the caked material

In contrast to this, when the polyol is treated with AEROSIL® fumed silica or SIPERNAT® precipitated silica, this is reliably avoided. An example of xylitol treated with 1 wt% SIPERNAT® 50 S is shown in figure 3 on the right side. Under the same storage condition, the particles do not agglomerate or form lumps. It is still an easyto-handle, free-flowing powder. It reaches the flow grade 3.

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Pharma & Healthcare News >> Besides the obvious reduction in hardness, the importance of adapting the mixing procedure can be seen in figure 4. Depending on the material itself, the silica used and the dosage, it is necessary to adjust the mixing time in combination with shear-intensity.

In this case, short mixing time at medium shear intensity resulted in the best anti-caking effect. Furthermore, other tests have shown that to reduce the caking of very fine powders, silica with fine particles itself offers the best performance like e.g. AEROSIL® 200 F. Dustiness - another aspect to be taken into consideration By reducing the adhesion forces of fine powders, the individual particles become freely movable and separate from each other. Because of this, it might happen that the dustiness of this powder increases. As dust is inconvenient and a possible irritant during manufacturing and packaging processes it needs to be avoided reliably.

When it comes to very fine powders, especially SIPERNAT® 350 outperforms other flow aids with regard to both reduced caking and no dust.

Here a dosage of about 0.4 wt% is already sufficient to reduce the caking significantly without increasing the dustiness. Higher dosages might bring only a limited additional advantage with regard to hardness of lumps, but there is the risk to generate some dust. Consequently, the type of flow aid used and its dosage need to be optimised carefully.

Summary and Recommendation Depending on the causes of caking and poor flowability of powdered sugars, the type of flow aid used and the mode of addition should be cho sen accordingly. In figure 5, the dif-

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Figure 5: Reasons for caking of carbohydrates and mode of action of silica.

Humidity without silica

with AEROSIL® or SIPERNAT®

Particle size without silica

with AEROSIL® or SIPERNAT®

ferent reasons for caking and the effects of silica are summarised.

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In case of hygroscopicity, moisture absorption is the main challenge. Silica with a high absorption capacity, such as SIPERNAT® 50 S, will be beneficial.

When the particle size or fineness of the carbohydrate is the limiting factor for the flowability, flow aids like AEROSIL® 200 F or AEROSIL® 380 F are good choices. Because of their particle structure, they improve flowability of small-sized powders very efficiently.

For special applications where, besides flowability, dustiness is an important aspect SIPERNAT® 350 offers a very good performance. Because of its fine particle size, it improves flowability efficiently, but does not increase dust

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For all powders, the mode of mixing the flow aid into the material has a significant influence on the effectiveness of the silica

Adapting the flow aid used, its dosage and the way of processing it depending on the individual condition and requirements, will finally lead to a product with optimal powder and handling characteristics.

References [1] “Zucker und Zuckerwaren”, H.Hoffmann, W. Mauch. W. Untze, Behr’s Verlag, p53ff [2] “Polyols in Confectionery”, British Journal of Nutrition (2001), 85, Suppl. 1, p31ff [3] „Handbuch Alkoholfreie Erfrischungsgetränke“, Südzucker AG (1998) [4] TI 1351 „SIPERNAT® and AEROSIL® as Flow Aid and Anticaking Agent“, Technical Information, Evonik Degussa GmbH, September 2008

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KLEPTOSE®: multi-functional excipients for molecular encapsulation Molecular encapsulation with native and modified cyclodextrins offers attractive and alternative tools in formulation development

By Elham Blouet, Pharmaceutical Project & Development Manager, Roquette To cover the specific needs of the pharmaceutical and cosmetic industry, Roquette offers a range of KLEPTOSE® products: β-cyclodextrins, hydroxypropyl β-cyclodextrins and methylated β-cyclodextrins.

The versatile excipient Cyclodextrins (CDs), native and modified, have the ability to form inclusion compounds through molecular encapsulation with a wide range of organic molecules. This ability makes the CDs and their derivatives valuable as formulation aids. They are used to increase aqueous solubility of poorly soluble drugs and consequently to avoid the use of organic solvents.

Their use is also of great interest for improving physical and chemical stability of drugs (protection against

light, oxidation, etc.), for enhancing local tolerance of drugs and for any other applications where inclusion compounds would enable innovative solutions. Medicinal products containing cyclodextrins and their derivatives are world-wide marketed including, among others, oral, parenteral, topical and eye preparations.

Native cyclodextrins CDs are cyclic oligosaccharides obtained from starch by enzymatic cyclisation using cycloglycosyltransferases. They are composed of α-(1,4) linked glucopyranose subunits. Several native cyclodextrins ex ist; the most referenced ones being α-cyclodextrin, β-cyclodextrin and γ-cyclodextrin constituted of 6, 7 or 8 α-(1,4) glucopyranose units respectively. β-cyclodextrin (βCD) is the most accessible and useful one with a significant industrial usage.

Advantages for HPβCD for the pharmaceutical industry and patients

KLEPTOSE® Kleptose is Roquette’s brand name for β-cyclodextrin (βCD). The βCD molecule is a torus shaped ring. Due to the spatial distribution of its hydroxyl groups, the βCD molecule has a polar hydrophilic outside and an apolar hydrophobic cavity. As a consequence of this particular structure, βCD is, when in presence of water, able to encapsulate or entrap guest molecules to form the so-called inclusion compounds. βCD is a crystalline, homogeneous, non-hygroscopic substance with a low aqueous solubility (approx.1.85% at room temperature). It is currently considered to be an essentially nontoxic and non-irritant ingredient, authorized for food applications and used in oral and topical pharmaceutical applications. Due to its nephrotoxicity, βCD is not suitable for parenteral applications. (continues >>)

KLEPTOSE® - main applications and benefits Pharmaceutical field: • Increase poor aqueous solubility of drugs with subsequently increased dissolution rate and hence improved bioavailability • Increase physical and chemical stability of drugs (increase shelf-life and reduce time to market) • Enhance local tolerance after topical or oral administration • Improve organoleptic properties of drugs (taste and/or odour masking) • Enhance drug delivery to and through biological membranes • Prevent drug-drug, drug-excipient interactions and drug-container interaction • Convert oily/liquid or volatile material into stable/microcrystalline powder • …

Cosmetics field: • Fragrance masking or release • Delivery of specific substances • Enhancement of UV filter activity • Reduction of local irritation

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Modified cyclodextrins The native CDs can be chemically modified by hydroxyalkylation, alkylation or sulfoalkylation. The principal aim of such modification is to increase the solubility of the parent native cyclodextrins.

The hydroxypropyl betacyclodextrin (HPβCD) has the highest aqueous solubility (65% at 25°C) and combined with its safety profile it represents an ideal profile for pharmaceutical applications. The high aqueous solubility of modified cyclodextrins HPβCD allows extension of the applications as the method of preparation of the inclusion compounds is easier compared to native βCD (in aqueous solution versus in semi-solid state, “kneading method”). Thanks to its safety profile, the HPβCD is a suitable excipient for parenteral applications as well as for oral, topical and ophthalmic applications.

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KLEPTOSE® CRYSMEB EXP The pioneering product, ROQUETTE’s KLEPTOSE® HPB derivative, has now been successfully marketed and used for several years. KLEPTOSE® CRYSMEB EXP is a second-generation product which has several advantages including the possibility of increased solubilization power while maintaining a high biological tolerance.

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KLEPTOSE® CRYSMEB EXP is a mixture of methyl βCD containing on average 4 methyl groups per native βCD molecule (i.e. a typical MS of 0.57). Due to its high aqueous solubility (20% at 20°C), it dissolves easily in water (unlike βCD), and solubility increases with temperature.

KLEPTOSE® CRYSMEB EXP can also be used in cosmetics for different aims, in particular for solubilization or stabilization of ingredients.

As with the KLEPTOSE® HPB, the KLEPTOSE® CRYSMEB EXP can be used in pharmaceutical applications with different aims:

Grades

KLEPTOSE® HPB / KLEPTOSE® HP Roquette has developed a range of substituted HPβCD with different degrees of substitution (DS = number of hydroxypropyl groups per molecule of βCD) as described by the Molar Substitution value (MS = average number of hydroxypropyl groups per anhydroglucose unit). KLEPTOSE® HPβCD derivatives, KLEPTOSE® HPB and KLEPTOSE® HP - are suitable for the cosmetic and pharmaceutical industries, including a pyrogen free grade produced under cGMP conditions for parenteral applications.

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to increase water solubility and rate of dissolution of poorly soluble drugs to increase the rate of transfer of a drug from solution into tissue without damaging the tissue to reduce side effects of active ingredients to reduce bitterness or unpleasant odour of some drugs.

Early preliminary toxicological information indicates that this methyl βCD shows potential for the development of injectable products and should be further investigated by formal toxicity studies.

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Heavy metals: an overview of European legislation Jost Chemical, who offers minerals that meet the most restrictive levels in the EU regulation, provides here a brief sum up of the new legislation on heavy metals in connection with minerals

By Jost Chemical In order to improve the protection of human health, European regulations are getting more and more precise and restrictive regarding the levels of contaminants in food and nutritional products.

As far as heavy metals are concerned, there is a number of existing regulations that concern mineral salts.

Is my mineral salt a food additive?

Some mineral salts are considered food additives (e.g. Ca carbonate, Ca citrate, Ca gluconate, Ca hydroxide, Fe gluconate, Fe lactate, K gluconate, …)

These must be in compliance with the purity criteria defined for food additives described in the regulation 2009/10/EC of 13 February 2009 amending Directive 2008/84/EC. What about the recent regulations 2006/1881/EC and 2008/629/ EC which set limits on contaminants in foodstuffs and food supplements?

As indicated, these regulations define the maximum levels of heavy metals in the final products (foodstuffs and food supplements) as Pb<3ppm, Cd<1ppm, Hg<0.1ppm).

Raw materials, including mineral salts, are not directly concerned.

However, in food, and especially in food supplements, a high concentration of mineral salts can occur in some products (multi-mineral food supplements, for instance, or Zn-enriched product).

What about the existing or future local regulations?

In addition, local regulations based on 2006/1881/EC and 2008/629/EC setting limits for heavy metals levels in raw material could appear in the short term.

In France, there is already a local regulation applicable to products that are not in the additives list and for which there is no existing monograph (USP, EP, FCC, …): these products (Zn lactate, Cu oxide, Cu citrate, Mn lactate, …) must comply with the following specifications: Pb<5ppm, As<2ppm, Cd<1ppm, Hg<1ppm.

Guaranteed highpurity minerals Jost Chemical has been producing guaranteed highpurity minerals for nearly 25 years and is now also wellknown for the development of a new technology for manufacturing of ultra-pure calcium salts for infant formulations and drink applications.

In order to offer our customers an added value to face these new regulatory challenges, Jost Chemical has decided to offer dedicated products whose specifications include a compilation of the most restrictive levels in the EU regulations: Pb<1ppm, As<1ppm, Cd<1ppm and Hg<0.1ppm.

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SEPIFILM™ LP - the breakthrough in moisture protection SEPIFILM™ LP is a ready-to-use, gastro-soluble composition for film coating of moisture sensitive solid particles

By Seppic SEPIFILM™ LP is a granular co-processed formulation which guarantees a homogenous formulation, an easy handling without dust, and a fast and easy dispersion without generation of lumps.

SEPIFILM™ LP is typically formulated from the following ingredients: • Film forming agent: HPMC • Binder: cellulose • Hydrophobic plasticiser: stearic acid • Colorants: pigments, lakes

comply with current editions of European, US and Japanese pharmacopoeias.

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Food applications: constituents of SEPIFILM™ LP are allowed for food applications in Europe and USA. For dyes: permission of use may differ from one country to another. Please consult us for specific requests. Our colour guide can help you in your choice.

SEPIFILMTM LP • Improves stability of moisture sensitive actives • Improves stability of hygroscopic formulations • Global acceptance: pharmaceutical and food/nutritional applications • Easy handling, fast and easy dispersion • Disintegration time not modified

SEPIFILM™ LP contains microcrystalline cellulose which makes it possible to decrease coating time, to enhance the film adhesion, and to avoid logo bridging.

Tablets coated with SEPIFILM™ LP exhibit an improved resistance to moisture, allowing the use of higher permeability packaging materials.

Unlike tacky PVA formulations or acrylic polymers, SEPIFILM™ LP is easy to handle, process, and clean as a classic coating based on HPMC. Regulatory status • Pharmaceutical applications: constituents of SEPIFILM™ LP

Reduced moisture permeability Water vapour transmission rates have been measured on four film coatings.

The results, which are shown in the graph below, demonstrate that SEPIFILM™ LP shows significantly lower moisture permeability compared to

Water vapour transmission rates

classic HPMC or PVA based formulations.

Dissolution profile As shown in the chart below, SEPIFILM™ LP does not significantly change the dissolution profile of coated tablets. (continues >>)

Dissolution test of coated Theophyllin tablets

Mg / h m

Dissolved Theophyllin (%)

120

SEPIFILMTM LP clear

SEPIFILMTM LP white

HPMC + PEG400

100 80 60 40 20

0

PVA

9

HPMC 15 cps

SEPIFILMTM LP 761

HPMC + TiO2 + PEG

Time (min)

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The Alsiano Healthcare team It is always nice to be able to put a face on the person you talk to over the telephone or e-mail. So here we are ...

Pharmaceuticals - cosmetics health & nutrition

Key accounts

Pharmaceuticals - cosmetics health & nutrition

Anders Hager

Lene Aarøe Nissen

Annette Strarup

M.Sc. Chem.

Sales manager

B. Chem. Eng. Area sales manager

B.Sc. (Hons.) Chem. Eng. Area sales manager

E-mail: ahg@alsiano.com Tel. dir.: +45 8230 0026 Mobile: +45 2618 8545

E-mail: lan@alsiano.com Tel. dir.: +45 8230 0025 Mobile: +45 2270 1002

E-mail: ask@alsiano.com Tel. dir.: +45 8230 0049 Mobile: +45 2270 1015

Pharmaceuticals - Fermentation

Sales support

Sales support

Annette Jarlskov

Signe Mørck

Birgitte Falkensteen

M.Sc. Food Science Area sales manager

Sales assistant

Sales assistant

E-mail: aja@alsiano.com Tel. dir.: +45 8230 0072 Mobile: +45 2270 1017

E-mail: sm@alsiano.com Tel. dir.: +45 8230 0042

E-mail: bf@alsiano.com Tel. dir.: +45 8230 0006

Sales support

Logistics Malene Rask Harder

Lene Baldasano del Valle

Sales assistant

Logistics manager

E-mail: mrh@alsiano.com Tel. dir.: +45 8230 0007

E-mail: lb@alsiano.com Tel. dir.: +45 8230 0015

>> Good Manufacturing Practices (GMPs) In addition to its ISO 9001 and ISO 14000 certifications, SEPPIC follows the IPEC1 Good Manufacturing Practices guidelines for its SEPIFILM™ and SEPISPERSE™ Dry product lines.

IPEC : International Pharmaceutical Excipient Council 2 AFSSAPS : Agence Française de Sécurité Sanitaire des Produits de Santé (the "French FDA") 3 ICH-Q7A: International Conference of Harmonization. Q7A: Good Manufacturing Practices for Active Pharmaceutical Ingredients

SEPPIC was also successfully audited by the French Drug Agency (AFSSAPS2) according to the BPF part II (ICH-Q7A)3 guidelines. Injectable and oral route excipients, which include SEPIFILM™ and SEPISPERSE™ Dry product range, were audited.

The analytical specifications warranted are only those mentioned on the certificate of analysis supplied with each delivery of the product.

Except as set forth above, SEPPIC* makes no warranties, whether express, implied or statutory, as to the product which is the subject of this document. Without limiting the generality of the foregoing, SEPPIC* makes no warranty of merchantability of the product or of the

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We thank all our customers for a good cooperation during 2010 and wish you a Merry Christmas and a Happy New Year

fitness of the product for any particular purpose.Buyer assumes all risk and liability resulting from the use or sale of the product, whether singly or in combination with other goods.

The information set forth herein is furnished free of charge and is based on technical data that SEPPIC* believes to be reliable. It is intended for use by persons having technical skill and at their own discretion and risk. Since conditions of use are outside SEPPIC*'s control, SEPPIC* makes no warranties, express or implied, and assumes no liability in connection with any use of this information. Nothing herein is to be taken as a license to operate under or a recommendation to infringe any patents

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