RESEARCH

STRATEGIES FOR

PHARMACEUTICAL

ENTERPRISES

Industriy research requirements and future technology and

management trends - The activities of pharmaceutical focus group

Emilia-Romagna Region

This publication was realized by ASTER Science Technology Business in collaboration with TEFARCO INNOVA and with the support of theEmilia-Romagna Regional Ministry for Productive Activities, Economic Development and Telematic Plan.

All information here reported was collected either directly or from previously published sources.

Special thank goes to the Enterprises, the Academic Research Groups and to the Laboratories of the Emilia-Romagna High-Tech Network,for their partaking in the activities of the Pharmaceutical focus group:

ACME S.R.L.ALFA WASSERMANN S.P.A.

AMBROSIALAB S.R.L.CHIESI FARMACEUTICIDOPPEL FARMACEUTICI

ERATECHFATRO S.P.A.IMA S.P.A

MEDEL S.P.ANILFISK-CFM S.P.A.OPOCRIN S.P.A

ASC LAB ER-GEN TECH GeBBA-Lab

UNIVERSITÀ DI BOLOGNADipartimento di Scienze Farmaceutiche - Gruppo di Chimica Farmaceutica Computazionale

Dipartimento di Elettronica, Informatica e Sistemistica - Laboratorio di Ingegneria Cellulare e Molecolare per lo Studio deiBionanosistemi

UNIFEDipartimento di Scienze Farmaceutiche - Gruppo Farmaceutico Tecnologico Applicativo

UNIVERSITÀ DI MODENA E REGGIO EMILIADipartimento di Scienze Biomediche - Gruppo di Farmacologia Molecolare e di Farmacogenomica

Dipartimento di Scienze Farmaceutiche - Laboratorio di drug discovery di inibitori enzimatici (LADDIE)Dipartimento di Scienze Farmaceutiche - Centro di Ricerca sulle Tecnologie Farmaceutiche Tradizionali ed Innovative (Te.Far.T.I.)

UNIVERSITÀ DEGLI STUDI DI PARMADipartimento di Ingegneria Meccanica - Area di Meccanica Applicata alle Macchine

Dipartimento Farmaceutico - Gruppo di Chimica FarmaceuticaDipartimento Farmaceutico - Gruppo di Tecnologia Farmaceutica

Published in Bologna – December 2007 – 1st EditionRealizzazioni grafiche I MUSICANTI NON DORMONO MAI info@musicanti.eu

INTRODUCTIONThis document summarizes the main outcomes of a groupdiscussion focused on the Pharmaceutical sector.

Eleven regional enterprises, representative of the Emilia-Romagnahuman and veterinary pharmaceutical industry, including both theproduction and manufacturing sectors, have been invited to expresstheir position on the scientific and economic challenges they meeton the way towards the development of new pharmaceuticalproducts. Researchers from regional academic institutes andleading actors of the Life Sciences Laboratories of the Emilia-Romagna Hi-tech Network have been also invited to take part tothe discussion, in order to draw possible scientific solutions on thebasis of their competences.

The working group activity was organized by Aster in cooperationwith the Regional Centre for the Innovation of Health Products,TEFARCO INNOVA. The activities were conducted by mean of thefocus group methodology, with the major goal to improve thedialogue between enterprises and researchers and to speed-upfuture interactions.

THE CONTEST AND THE“FOCUS GROUP” METHODOLOGYIn the last years, Emilia-Romagna Government overall strategy hasbeen strongly intended to support Industrial Research andTechnology Transfer, with the main purpose to invest in theknowledge and innovation-based development of the regionalproduction system. ASTER contributes to this policy issue bypromoting the co-operation between universities, research centres,enterprises, financial markets and consulting services, so as toestablish a regional framework where human resources can bereinforced and knowledge can be spread out and integrated.

Since 2004 Aster has been coordinating the creation of the Emilia-Romagna High-Tech Network, connecting scientific competences,which share human resources and advanced instrumentation. From2005, thanks to the Regional Programme for Industrial Research,Innovation and Technology Transfer (PRRIITT), 5 “NetworkedRegional Laboratories” focused on Life Science and relatedtechnologies have been created.

Among these, there is one centre specifically focused on thepharmaceutical sector and two laboratories whose researchactivities are strictly connected to this sector:

TEFARCO INNOVA – Regional Centre for Innovation ofPharmaceutical and Health Products, coordinated by theUniversity of ParmaASC LAB – Stem Cells for Tissue Repair, coordinated by theUniversity of Bologna and soon to be transferred inside the newlaboratory of the IRET Foundation of 1600 square metersR-GenTech – Emilia-Romagna Genomic and BiotechnologyInnovation Laboratory coordinated by the University of Ferrara,with facilities in Bologna, Modena and Ferrara

The focus group initiative, recently launched by Aster consists in aseries of guided discussions conceived to explore, in a group setting,what participants think and how they feel about previously decidedthemes. Participant of the group discussions are regionalenterprises and academic research actors, faced in order to find acommon way to overcome the perceived bottlenecks in thedevelopment pathway of a specific industrial sector. Three focusgroups on the Mechanic, Food and Life Sciences sectors have beenalready carried out and others will be established in the near future.

THE RATIONALE FOR THEPHARMACEUTICAL SECTORAccording to the latest report published by the industrial associationFarmindustria, the Italian pharmaceutical industry is quite strong,ranking the third position in the European economy and the fifth atworld level. The sector, which faced a crisis in the late 1990s, todayaccounts for 340 enterprises and more than 70 thousandemployees. Among the Italian enterprises, there are many bigcompanies with more than 250 employees and a larger number ofsmall and medium-sized businesses with promising developmentpotential, which account for almost 20 thousand jobs.

In this contest, Emilia-Romagna is one of the leading regions of theItalian Pharmaceutical industry. Regional companies are few (11),but they encompass 3500 employees, especially concentrated inthe area of Parma and Bologna.

These two cities rank in the first ten provinces in Italy in terms ofnumber of employees, with the presence of two industrial colossal:the Chiesi group based in Parma and Alfawassermann in Bologna.

The continuous emergence of new diseases that require the fastdevelopment of chemical substances with a therapeutic effect givesto the pharmaceutical market a highly competitive nature andindissolubly links it with the scientific research for the generation ofinnovative products.

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Accordingly, Italian industry is strongly directed towards R&Dactivities, giving rise to a 77 pharmaceutical product pipeline.Among these, we can count 35 drugs in the pre-clinic phase and 42on clinic experimentation, of which 60% are biotech products. The74% of the Italian clinical trials are conducted in Emilia-Romagna,basically supported by local enterprises.

The long and risky pathway towards innovative medicines can befacilitated by fostering of the research centres and industrialcompanies to jointly tackle the challenges arising by emergingdiseases. The promotion of science - industry partnerships in thepharmaceutical field is fundamental to achieve human and animalwellbeing through prevention, diagnostic and manufacturingtechnologies for an improved public health environment.

Keeping this in mind, the main objectives of the pharmaceuticalfocus group are:

to analyse the actual pharmaceutical industry challengesthrough the voice of a group of companies, representative ofthe Emilia Romagna area; to evaluate current barriers and constraints to pharmaceuticalindustry development and innovation and to draw possiblesolutions;to raise awareness of the results achieved, producing adocument which can be used as a driver for future regionalpolicy.

The starting point of the focus group activity came from a firstdiscussion group on the pharmaceutical sector, coordinated byAster in spring 2007 and established in the framework of theEmilia-Romagna Health Technologies Platform. A relevant output ofthis action was a document presented to the European Commissionin response to the public consultation on the future ofpharmaceuticals for human use in Europe, launched in July 2007.

The Pharmaceutical focus group and its outputs reported in thepresent document, has been intended to give a continuum to theactivities of the previous working group, enlarging the boundaries ofthe discussion also to the veterinary sector and putting moreemphasis on the enterprises point of view.

THE DISCUSSION THEMESBased on what emerged from the previous working group and onwhat reported to the European Commission, four technical themeshave been identified and discussed:

Drug discoveryDrug Delivery Systems

Medicine manufacturing and quality Efficacy, safety and dedicate instruments for analysis

1. Drug discoveryCrucial bottlenecks in this sector are, first of all, the severalchallenges arising from the molecular, gene or protein targetsdiscovery and from the identification of “drug-like molecules” activeon these targets. Secondly, the definition and interpretation of theeffects on biological complex systems and the validation of newtargets of therapeutic relevance. In this contest the lack of reliableanimal models becomes critical.

In order to overcome these difficulties enterprises must invest inemerging technologies of combinatorial synthesis, high-throughputscreening, bio/nanotechnologies, cellular and tissue engineering.The development of e-technologies and the progress in molecularbiology and pharmaco-informatics will help in modeling, simulatingand predicting a candidate substance with pharmacological,pharmacokinetic and toxicological properties.

2. Drug Delivery SystemsDrug delivery research focuses on the development of new drugadministration routes, leading to the product efficacyimplementation and to the patient compliance increase.

Major issues faced by pharmaceutical enterprises in this sector areon one hand, the numerous problems related to the emergingbiotech substances administration and, on the other hand, the needfor the development of medicines for children, different frommedicines designed for adults or for the elderly. The improvementof personalized medicines according to physical or genetic individualdifferences are also wide sectors of emerging interest.

Moreover, drug delivery technology is called to respond to thenecessity to have dosage forms for advanced therapy with biologicalelements. Important diseases of this century, such as cancer,Alzheimer, Parkinson, viral infections, tuberculosis, malaria, requireinnovation for the goal to hit the affected parts of the body withoutinvolving the healthy ones.

Finally, vaccination without needle still remains a challenge. In thisfield the new delivery technologies like microspheres, nanoparticles,ionophoresis, electroporation, colloidal vectors, delivery devices foralternative routes (inhalation, transdermal, buccal, vaginal, oral etc.)play a key role as far as they can change the drug propertieswithout chemistry intervention.

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3. Medicine manufacturing and qualityMedicine quality anticipates efficacy and safety requirements and iscritical for the delivery to the market of new products. Newconcepts are on the table of the manufacturing practices such asthe Quality by Design and Process Applied Technology, that areintended to support manufacturers guaranteeing quality in real timeand with high confidence level. Emilia-Romagna region is particularlyknown for its expertise in manufacturing machines. Themanufacturers are now considering a new approach to thepharmaceuticals market consisting in the proposition of newtechnologies of drug delivery coupled with new machines formanufacturing new drug delivery systems.

4. Efficacy, safety and dedicateinstruments for analysisThe collaboration in pre-competitive research for drug developmentis part of an EU iniziative known as IMI, Innovative Medicines Initiative. IMI addresses the causes of delay or bottlenecks in theR&D process in order to accelerate discovery and development ofmore effective innovative medicines with fewer side-effects. Thetargeted aspects include improved predictivity of non-clinical safety,translational safety biomarkers, immunogenicity, non-genotoxiccarcinogenesis, expert systems for in silico toxicity prediction,pharmacovigilance, islet cell research, surrogate markers forvascular endpoints, genetics and genomics of type 2 diabetes, butalso training programs on safety sciences, pharmaceutical andintegrated medicines development and pharmacovigilance.

INDUSTRY REQUIREMENTSThe delivery to the market of new pharmaceutical products is ahigh-risky, time-costly business, that involves many different actors.By the examination of this process, it clearly emerged that thefuture of the pharmaceutical industry is strongly dependent on amore intensive collaboration between all these actors, includingbiologists, chemists, clinicians, engineers, pharmacists and officialfunctionaries. Pharmaceutical companies, especially small-mediumenterprises, cannot afford all the expenses and the competencesinvolved in the production process and academic support is criticalfor them to remain competitive on the national and internationalmarket. Moreover, a crucial requirement for introducing a newproduct into the market is its efficacy, quality and safety certificationby health authorities. In this scenario, the enterprises expressedthe urgent need for the upgrading of current research laboratories,not yet equipped for operating in an environment recognized byhealth authorities, in light of the fundamental importance to obtain

research data collected in a GXP structure, suitable to directlyunderway the regulatory procedures. The solution to this problemcould pass through the development of academy and inter-department center consortia, where the academy bureaucraticslowness can be overcome and the time-schedule imposed by acompetitive market can be matched.

Key steps to be undertaken by academy for the creation of thesestructures are:

to facilitate company access to research activities and speedup the delivery process of reliable results;adoption by the research groups of transparent and welldefined procedures in terms of intellectual property, leading toan easier establishment of commissioned research activities;to reinforce the academic linkage with hospitals, in order toallow pre-clinical and clinical studies to be performed in thesame location.

The availability of recognized research centers will provide industrywith the following added values:

reduction of the number of contracts with foreign centers bythe national companies;improvement of the transfer of trained personnel from thesecenters to the companies;attraction of new commitments, also from foreign companies;use of the center in a combined way between the medicinemanufacturer and the manufacturing machine producer.

Finally, veterinary industries pointed out the emerging vigor withwhich animal health is influencing, during the last decade, humanhealth and food safety, in the light of the 90’s outbreaks of majoranimal diseases. At present several factors threaten the veterinaryindustry competitiveness, including the regional and more widely theEuropean regulatory framework and the increased development oftime and costs for new products faced by a sector mostlycharacterized by small enterprises. The need for a closecollaboration between veterinary and human companies can be animportant step towards the innovation of this sector. Indeed, animalresearch has the potential to produce important lessons for humanmedicine development and thus to speed up the process for thecontrol of key human diseases.

THE EMILIA-ROMAGNARESEARCH EXCELLENCESPharmaceutical research in Emilia-Romagna is rich andstrengthened by a wide range of scientific expertise. Competences

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in the sector range from chemistry, biology and biotechnology,pharmacogenetics and genomics to drug delivery and machinemanufacturing.

Taking into account the four themes discussed by thePharmaceutical focus group as reference, Emilia-Romagna scientificbase can support industry innovation and new medicinedevelopment by offering advanced competences especially on thefollowing areas.

New molecules and cellsComputational techniques for the design and screening of newmolecules Synthesis of new molecules Computational systems biologyStudy and characterization of molecules having innovativemechanisms of action Study of natural substances Methods of quick screening Pharmaco-genomics (database construction, genetic kits andmarkers for resistance or response)Luminescent cellular biosensors Cellular drugs

Clinical and preclinical testsDevelopment of bio-engineering methodologiesModels and animal protocols optimizationIn vivo ed in vitro models and protocolsIn silico models and protocolsPharmacokinetics and metabolism (ADME)Clinical shared database

Mew medicines, devices and materialsCombined products Preformulation studies Inhalation productsDrug delivery e targetingVeterinary medicinesPersonalized medicines Non-viral carriers for gene therapy

Manufacturing and quality of medicines Process engineeringMaterial/devices functionalizingContinuous processesAutomatic machines and validationSustainable automation

According to the reported analysis, the Emilia-Romagna region iswell equipped to become what we could define a “Drug Discoveryand Drug Delivery Region”, with the mission to discover, develop andmanufacture innovative medicines.

THE FOCUS GROUP RESULTS The focus group activity allowed to identify two concrete possibleanswers to the current challenges met by pharma -industries withinthe region.

First of all, universities called for a valorization campaign aimed atincreasing the industry awareness in the great resourcerepresented by the significant number of spin-offs recentlyestablished in the region. Actually these spin-off at the moment maybe considered the more effective interface between academy andindustry. The creation of new spin-off or start-ups should promotedand supported as well.

Secondly, all the participants, unanimously recognized the greatadvantage that would stem from the presence in the region of anadvanced pharmaceutical laboratory working in GMP for themanufacturing of bio-batches, lots of orphan drugs and structuredfor research activities to be conducted in a GLP regime. Thislaboratory could give to Emilia-Romagna a unique position in Europe,coping for the Emilia-Romagna industry competitiveness. Such kindof new facility is the target of a project proposed by TEFARCO Innovafor the generation of XL-PHARMA Lab, a new pharmaceuticalintegrated infrastructure, fully dedicated to industrial research andtechnology transfer, in the respect of the GXP certification.

This aspect, joint to the impulse toward the creation of new spin-offs, will reduce the existing gap between research and industry,leading to the creation of innovation processes more aligned tobusiness requirements.

CONCLUSIONSThe focus group allowed the industrial actors to interact directlywith researchers, giving insights on the actual challenges faced byregional pharmaceutical industry. In turn, the presence of universityresearchers provided quick and tailored answers and clarificationsto the issues raised by enterprises.

Moreover, the concurrent presence of human and veterinaryindustries allowed to highlight possible advantages stemming frominterdisciplinary research carried out with enhanced collaborationbetween groups skilled respectively on human and animal disease.

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In this context it is relevant the role of integrating structures like ASTERand TEFARCO for the promotion of specific initiatives addressed tofacilitate the dialogue between academy and industry. The focus groupexperience paves the way for futures synergies and co-operations forthe improvement of the competitiveness of the regional pharmaceuticalproductive context.

The results here reported are not intended to be exhaustive. Theyrather represent the initial stage of a more structured process to beimproved in the next future and hopefully supported by local, nationaland European policy actions.

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THE FOCUS GROUP ACTORSTHE COORDINATORTEFARCO INNOVA TEFARCO Innova is the Regional Centre for Innovation of HealthProducts coordinated by the Interuniversity Italian Consortium ofInnovative Pharmaceutical Technologies. Its activity focuses oninnovative technologies for health products that can be transferredto companies, in particular SMEs, active in pharmaceutical, foodand cosmetic fields.

TEFARCO major goal is to develop scientific potentialities of all Italianacademic partners by a unitary action of transfer of their productstoward the industries, by mean of direct contacts, researchcontracts, seminars and scientific communication, consultancy,publications in cooperation.

The intellectual and technical resources provided by the researchgroups of the Consortium are represented by high technologyproducts, such as preparations for therapeutic or health use, havinghigh innovative content and added value. The centre also offers post-graduate courses on the themes of quality and manufacturing ofpharmaceutical, nutracuetical and cosmetic products.

The constant connection with innovative research and educationcentres at national and international level, allow Tefarco Innova tobe constantly up-to-date for what concern scientific and trainingrequirements in the health products field.

For more information: http://www.tefarco.unipr.it/centro

PHARMACEUTICAL ENTERPRISESACME S.R.L.ACME s.r.l. is a veterinary pharmaceautical company set up in 1987in Reggio Emilia (Italy) as a company specialized in the production offood supplements and feeds for horses; soon ACME launches theproduction of its products for dog and cat. In 1994 ACME obtainsits first authorization to market a drug containing an anti-inflammatory for the therapy of the horses. To this day, ACMEmarkets drugs specifically for dogs, cats, horses, cattle and pigs inaddition to its production of complementary and high quality feeds,cosmetics, feeds for cats and dogs and fluid therapy.

ACME DRUGS, also based in Reggio Emilia (Italy) produces thedrugs marketed by ACME and an innovative product to controlfertility in urban pigeons. ACME DRUGS has developed high-leveltechnological know-how in the production of paste and granulesdosage forms for the pharmaceutical industry.

ACME and ACME DRUGS collaborate in the development andcarrying our of pre-clinical and clinical researches on animals’model and target species.

For more information: www.acmedrugs.com

ALFA WASSERMANN S.P.A.Founded in 1948, Alfa Wassermann SpA is a consolidatedpresence on the Italian pharmaceuticals market, researching,producing and selling both prescription and self-medicationspecialities. The headquarters and research laboratories arelocated at the original premises in Bologna, while there is a modernproduction unit at Alanno (Pescara). The International andDiagnostic Divisions are based in Milan.

Alfa Wassermann SpA promotes its products by means of anetwork of medical representatives who visit general practitioners,specialists and pharmacists as well as public and privatelaboratories. With a workforce of over 700, the company also actsas a holding company for the group (8 subsidiaries in Europe, USA,China and North Africa with more than 1,100 employees).

One of the strong points of Alfa Wassermann SpA is that more than60% of turnover is generated by its own products, developed by in-house research. Alfa Wassermann also has a Division marketingand selling non prescription specialities with an extensive networkof direct promoters to pharmacies.

Alfa Wassermann is also present in the human in vitro diagnosticsector. In Italy the Diagnostics Division distributes products byleading Japanese and American companies. This Division is thetechnical partner of choice for numerous colorectal cancerscreening initiatives supplying faecal occluded blood test kits.

For more information: www.alfawassermann.it

AMBROSIALAB S.R.L.Ambrosialab is an academic spin-off of the University of Ferrara. Itis an outsourcing source of applied research and services for

companies, institutes and clinics in pharmaceutical, cosmetic,nutritional fields.

Ambrosialab holds an authoritative know-how in the field of oxidativeprocess and posses a wide range of methods even exclusive(dermanalyzer) for the determination of the oxidative stress and ofthe antioxidant capacity of pure substances as well as complexsubstrates such are body fluids, foods, pharmaceutical, cosmeticand food supplements products.

Ambrosialab can evaluate by means of many different methods theanti-oxidative potential of any substratum, using both instrumentaltechniques (e.g. ORAC, PCL and DPPH test) and in vivo studies withnon-invasive bio-engineering methods (Dermanalyzer and SkinColor).By the use of a solar simulator, which has the characteristicsrequired by European and international regulation institutions(Colipa and FDA), we develop new strategies and original protocolsto test the efficiency of products aimed to protect the skin fromphoto-oxidative damages deriving from solar radiations.

Ambrosialab can offer complete scientific assistance in all steps ofthe project, from its drafting to the creation of a prototype suitableto be put onto the market, going from the identified molecule oractive principle to the training of the staff involved in the scientificdivulgation.

For more information: www.ambrosialab.com

CHIESI FARMACEUTICIThe Chiesi Group is a pharmaceutical company that researches,develops, manufactures and sells innovative prescription drugs.

In 2007 Chiesi invested more than 80 million Euro in R&D activities,with around 300 researchers, becoming one of the leading Italiancompanies in the sector. Chiesi employs more than 3.000 peopleand has a direct presence in more than 24 countries, in Europe,Asia and the Americas.

The Group’s main interests are the respiratory area, especiallyasthma and COPD, where Chiesi has developed a number of deliverytechnologies (sprays and dry powder inhalers), formulations (sprays,powders and nebulising formulations) and innovative products,neonatology, where Chiesi is world leader with Curosurf®,cardiovascular and the central nervous system.

Sectors of interest are:research projects in the respiratory area and rare diseases;

development projects in the respiratory area, cardiovascular,central nervous system and rare diseases;development of delivery systems and formulations;advanced therapies.

For more information: www.chiesigroup.com

DOPPEL FARMACEUTICIDoppel Farmaceutici was created in 1994 through a spin-off fromHoechst Roussel Group. Since its foundation, Doppel chose to be a"plain outsourcer": working only and exclusively on contractmanufacturing for other Italian and International PharmaceuticalCompanies.

Starting out with about 40 employees, in 10 years Doppel hasbecome one of the biggest Italian companies with an estimated 400people, two avant-garde production units in Italy (one inCortemaggiore, Piacenza and the other in Rozzano, Milan).andpartnership agreements with two very important Companies:Farmaceutici Procemsa in Turin and the Swiss I.P.A.S.

Doppel Farmaceutici is specialised in contract manufacturing of allgalenic forms especially: capsules, tablets, coated tablets,pharmaceutical and alimentary granules, suppositories, ointments,gels, creams, vaginal suppositories, drops, syrups, mouthwashes,vaginal washes, oral solutions in single-dose container with activeingredient reservoir cap, aerosol vials, sterile filling injectionampoules or ampoules with final sterilization; medical foods andnutritional supplements (Procemsa Farmaceutici). The company isalso allowed to manufacture small-scale batches for experimentalclinical use.

Doppel Farmaceutici can also offer a wide range of services suchas analytical development, formulation development, stabilitystudies (ICH), process development and scale-up, process validation,regulatory support, technology transfer and CTD compilation.

For more information: www.doppel.it

ERATECH S.R.L.Eratech is a drug development company specialized in the field ofinhalation drug delivery via nasal and pulmonary administration, forlocal and systemic therapies. The support offered by Eratech can beprovided at different levels moving from the simple consultingservice to the more sophisticated use of Eratech’s proprietaryformulation technologies. -

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Eratech’s know-how and technological expertise are diversified inthe following areas:

Liquid and dry powder formulation: design and lab developmentof inhalatory formulations using powder productiontechnologies (dry powder blending, spray drying andsupercritical fluidsFormulation characterization: definition of the critical propertiesof the formulation in terms of solid state, particle sizedistribution dry and wet, and stabilityAerosol performance: evaluation of properties like dispersibilityand in vitro deposition in combination with the inhalerScale-up: Eratech is capable of scaling-up the formulationsselected at lab scale for clinical and registration purposesClinical studies and registration: Eratech, in collaboration witha selected team of clinical experts, has the capabilities toidentify the ideal clinical strategy and conduct clinical trialsRegistration: Eratech’s team has several years of experiencein the registration of drug products for the Italian and Europeanmarket.

Eratech is very active in the identification of new innovativetechnological advancement in the area of inhalatory formulations.The broad list of new opportunities offered allows for theidentification of original products that are characterized by improveddispersibility, pulmonary deposition and sterility applicable to drypowders or liquid formulations.

For more information: www.eratech.it

FATRO S.P.A.Active in the veterinary pharmaceutical sector exclusively for sixtyyears, FATRO has been manufacturing vaccines and medicinalproducts for farm and companion animals. The FATRO stock capitalis fully private and Italian: in Italy it has more than 280 employees,and 80 technical scientific representatives who cover the whole ofthe national territory. Through the years, FATRO has developedconstantly, acquiring a high pharmaceutical technological level andachieving a leading position in Italy, thanks to investments inresearch, a strong marketing action and a widespread sellingnetwork in Italy and abroad.

Indeed, FATRO exports its products in 80 countries according toan international expansion plan which adjust strategies to thevarious local situations.

As regards the research and development sector, FATRO invests alarge share of its capital in order to obtain and introduce into the

market innovative and high-quality products; its R&D laboratoriesare GLP certified. In order ot satisfy EU requirements for thedevelopment of veterinary medicinal products, fully respecting thehealth and well-being of the animals, FATRO is also equipped withGLP-certified animals facilities in a conventional environment and ina confined one.

The key areas on which FATRO counts are: gynecology, anti-infectiontherapy, metabolic therapy, liver therapy, anti-deficiency andprevention (vaccines), by means of originally developed products.

In its facilities of Ozzano Emilia (Bologna, Italy), all the products andvaccines for cattle, swine, sheep and goats, rabbits and fish aremanufactured, whereas avian vaccines are manufactured in thefacilities of Maclodio, (Brescia, Italy).

In addition to production facilities in Italy, there are production unitsin Poland, Argentina and the Czech Republic. Moreover, some vet-pharma companies have been totally or partially acquired in Spain,Greece, India, Uruguay and Mexico.

For more information: www.fatro.it

OPOCRIN S.P.AOpocrin is a company active in research, production and marketingof active pharmaceutical ingredients (APIs). Through its R&DLaboratories, the company has also focused on researchinginnovative APIs with high therapeutic value.

The company is particularly interested in the following researchareas:

pathologies that are connected with haemostasis andthrombosis, typical of industrialized countries;ophthalmic and gynaecologic pathologies.

In order to balance the high risks of the medium-long term projectsneeded to develop innovative drugs, Opocrin’s strategy aims atincluding in its product portfolio also medical devices, controlledrelease pharmaceutical substances and new forms ofadministration for drugs with high tolerability.

The main APIs currently produced and marketed by Opocrin are:Parnaparin, Lung Surfactant, TSP (Tamarind Seed Polysaccharide),Catalase, Sodium and Calcium, Heparin, Mesoglycan, Sulodexide,Dermatan Sulfate, Iron Complexes (Sodium Ferric Gluconate; IronSucrose; Ferric Protein), ANTEMA®.

Opocrin is mainly active in the production of active pharmaceutical

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ingredients to be used in thrombohemolytic troubles, prevention ofpostoperative thromboembolism, dialylsis (such as Parnaparin andSodium and Calcium Heparin) as well as in the treatment of deepvenous thrombosis (Dermatan Sulfate). Opocrin has recentlyenlarged its APIs product range by introducing TSP (active principleused as artificial tear) and some Iron Complexes such as SodiumFerric Gluconate, Iron Sucrose and Ferric Protein. Besides theseAPIs, Opocrin has developed ANTEMA®, a medical device used asa haemostatic adjuvant in the healing process of acute/chronicvascular, traumatic and decubitus ulcers.

For more information:

MECHANIC MACHINESMANUFACTURE ENTERPRISESIMA S.P.AEstablished in 1961, IMA is the world leader in the design andmanufacture of automatic machines for the packaging ofpharmaceutical products and of tea in filter bags. The Group has more than 3,000 employees, more than 1,400 ofwhom overseas, and a consolidated turnover of 425.2 million Eurofor the fiscal year 2006, with more than 92% earned oninternational markets. The pharmaceutical sector, which ischaracterised by a high and constant growth rate, accounts for83% of the Group's sales (17% is in the tea sector).

IMA can count on 17 production plants in Italy, Germany, the UnitedKingdom, the Netherlands, the United States, India and China. IMAhas an extensive sales network comprising 9 branches whichprovide sales and service in France, the United Kingdom, Germany,Austria, Spain, Portugal, the United States, China and Thailand,representative offices in Central and East European countries andover 50 agencies covering a total of more than 70 countries. IMAis also participating in 2 joint-ventures in China for production andservice.

IMA has recently acquired the freeze-drying machinery business ofthe BOC Edwards Pharmaceutical Systems Group, undisputedleader in this sector and with its main office in the Usa. IMA S.p.A.has been listed on the Milan Stock Exchange since 1995 and in2001 joined the STAR segment. The following companies are partof the IMA Group: Co.ma.di.s. S.p.A., IMA Flavour S.r.l., IMA KilianGmbH & Co. KG, IMA Libra S.r.l., IMA Safe S.r.l., Nova PackagingSystems Inc., Precision Gears Ltd., Swiftpack Automation Ltd.,

Zanchetta S.r.l.

For more information: www.ima.it

MEDEL S.P.AMedel designs and manufactures, since 1966, inhalation devices,aerosoltherapy systems, disgnostic equipment and other productsfor the home healthcare. Medel is driven by Research andDevelopment, which works in close relationship with the medicalcommunity world and several pharmaceutical companies. Severalmilestone in the nebulizer history were set by Medel: latest R&Defforts materialized in the development of a unique and patentedtechnology that considerably reduced the size of nebulizer systems,now the size of a cellular phone, battery operated. This technologyhas made life of millions of asthma patients worldwide an easierand a better one. Medel products are distributed in the bestpharmacies and medical shops worldwide: more than 60% of salesare made abroad, in more than 70 countries, from U.S. to MiddleEast, from Europe to Japan.

Drug delivery via inhalation for pulmonary applications;aerosoltherapy; nasal inhalation; inhalation; diabetes control andtherapy; diagnosis and prevention of hypertension; measurement ofbody temperature.

For more information: www.medel.it

NILFISK-CFM S.P.A.Nilfisk-CFM is world leader in the production of industrial vacuums,pneumatic conveyors, centralized vacuum systems, high powervacuums. Thanks to the high specialization, Nilfisk-CFM is partner ofthe biggest production companies such as Roche, AlphaWasserman, CIBA, IMA, Volkswagen, Barilla, Ferrari, Fiat... Nilfisk-CFM core business are industrial vacuums, 40 basic models andmore than 500 versions able to satisfy the needs of many differentsectors.

In its continuous endeavor to achieve total customer satisfaction,Nilfisk-CFM has always given priority to the development of “special”products, expressly made for specific applications. The mostdemanding sector is the chemical-pharmaceutical one and it’sprecisely for these customers that Nilfisk-CFM developed acomplete range of dedicated products to meet their requirements:the WHITE RANGE. Designed to comply with the strictest Europeanand worldwide norms and regulations, today the Nilfisk-CFM whiterange can satisfy also the most exigent market’sneeds, even in hazardous environments in full compliance

with the ATEX directive.

The white range satisfies the safety and quality exigencies, that aretypical of this sector granting the maximum hygiene and preservingthe product quality and the operator’s health. Think only about thefeatures of this line: small size, wide filtration surface, high silence,absolute filter and/or special filters for toxic dust (L-M-H). The whitemachines can be realized in stainless steel or in ATEX flame-proofversion. Nilfisk-CFM offers high quality products to its customers, infact Nilfisk-CFM has obtained the most important and selectiveInternational certifications such as ATEX, IECEx, TÜV, GS, Ce, CESIand for the quality procedures Vision 2000.

For more information: www.nilfisk-cfm.com

EMILIA-ROMAGNA HI-TECH NETWORK LABORATORIESASC LABStem Cells for Tissue Repair: Development of Products andProtocols for Research LaboratoriesResearch at ASCLAB is intended to bridge the gap existing in thestudy of the alternative uses of stem cells in reparative medicinethrough: (1) the creation of a bank collecting embryonic stem cells(eSCs) and adult stem cells (aSCs) derived from different animalspecies and grouped according to species-specific proliferation anddifferentiation characteristics and (2) the development and transferof protocols for the use of stem cells to national as well asinternational research centres.

The main scientific activities can be summarised as followsAnalysis of the proliferative activities of eSCs and aSCs derivedfrom the tissues of various animal species (e.g. cattle, horses,cats, dogs and mice)Analysis of the lineage of eSCs and aSCs from a neuralperspective (i.e. astrocytes, oligodendrocytes and neurons)Study of the role of micro-environmental signals in phenotypicaldifferentiationDevelopment of a skin stem cell bank and skin organotypicculturesStandardization of the use of eSCs and aSCs forpharmacological and toxicology studies

When all objectives are achieved, a number of technologies can betransferred to business and research partners such as protocols

for the production of clones derived from eSCs and aSCs;cryopreserved primary cultures of astrocyte and oligodendrocytesand, finally, protocols for the production of neural cells and for theircharacterisation by means of RT-PCR, real time PCR,immunocytochemistry and cytofluorimetry.

For more Information: http://www.aster.it/asclab.html

ER-GENTECHEmilia-Romagna Genomic and Biotechnology InnovationLaboratoryThe laboratory specialises in genomics research and thedevelopment of innovative biotechnologies with the objective ofbecoming a centre of excellence for the transfer of newtechnologies to the biotech and pharmaceutical industries as wellas to medical practice, thus narrowing the gap existing betweenbiotech/genomics research and industry applications and reducingthe delay with which research outputs are accessed by the industry.

ER-GenTech is currently conducting research in a number of keyareas:

Genomic and post-genomic analysis of the ageing process,tumour growth processes and chronic diseasesDevelopment and implementation of “decoy” molecules able toalter the expression of genes that play a key role in humandisordersDevelopment of last-generation viral carriers for theintroduction of recombinant proteinsCreation of engineered proteins that play a key role as“biosensors” of cell parameters to be used in the functionalanalysis of normal and pathological cells and for drug screeningpurposesDevelopment of protocols for the use of engineered proteins tocreate innovative therapies to cure widespread pathologicalconditions such as hyper-cholesterolaemiaAnalysis of the self-regeneration and differentiationmechanisms of stem cells aimed at developing treatments forthalassaemia, osteoporosis and osteopenia

For more Information: http://www.ergentech.it

GEBBA-LABVirtual Laboratory for the Application of Bioinformatics toGenomics and Medical BiotechnologiesMain aims of the lab are:

integration of ICT, Bioinformatics and Biology researches;

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application of bioinformatics to innovative technologies forgenomics and medical biotechnologies;synergy between the public research system and theindustries.

The activities of the lab currently focuses on three bioinformaticsapplications:

Softwares for data management: GeBBA produced GePh-CARD (Genotype-Phenotype Correlation, Analysis and ResearchDatabase), an information repository that allows a completeanalysis of genetic and clinical data. This DBs create reports,perform statistic analysis and collect epidemiological dataMicroarray data analysis: a service able to organize all theinformation related to the microarray analysis and to integratethem with analysis tools of quantified microarray hybridizationdata. This service can be accessed at various level: fromstorage and database organization, to data analysis and mining,and on-line reportingExpression data analysis tools for the identification of SingleNucleotide Polymorphisms (SNP). A new expression dataprojection tool working at the genomic level is currently beingdeveloped including specific protocols for the study of new RNAsuch as microRNA

GeBBA-Lab is also interested in establishing connections withsimilar laboratories in other European countries, in exchangingknowledge and creating productive synergies.

For more Information: http://www.gebbalab.it/

EMILIA-ROMAGNAUNIVERSITY DEPARTMENTSUniversity of Modena e Reggio EmiliaDepartment of Biomedical Sciences:Molecular Pharmacology and Pharmacogenomic research groupThe laboratories of Molecular Pharmacology andPharmacogenomics are situated at the Department of BiomedicalSciences which counts more than 200 researchers covering thevarious biological aspects related to health, disease and therapy.The effects of that a drug may have on living systems are analyzedat different levels that range from its effects on DNA to the functionof proteins up to the most complex integrative and behavioralsystems. This type of research is carried out both in extremelysimplified in vitro models using for example cell cultures, as well asin vivo using various types of animal models.

Current research is focused on the identification andcharacterization of new molecular targets underlying drug action.

At present the main lines of research are:The study of genes and mechanisms involved in the action ofantidepressant drugsGenetic mechanisms underlying drug resistanceThe development of new models (both at the cellular andanimal) that may provide a more efficient study of drugs andtheir actionAll key techniques used in molecular pharmacology andpharmacogenetic studies: receptor binding, in vitro models forthe study of drug action, behavioral and genetic animal models,proteomics, gene expression (real time PCR gene CHIP),genotyping

For more Information: www.dsb.unimo.it

Department of Pharmaceutical ScienceMedicinal Chemistry group, Drug Discovery of Enzyme InhibitorsLaboratory, (LADDIE)LADDIE is located in the Department of Pharmaceutical Science(SciFarm), that represents the main department of research in thefield of Drug Discovery at UNIMORE. The main research expertisesof the Department are molecular modelling, advanced syntheticchemistry, analytical tool, enzymatic screening and drug delivery.

The Medicinal Chemistry area is focused on anticancer,antinfectives and antiadrenergic drugs. A research centre (Tefarti)and a Spin-Off (Tydockpharma) have been developed among thetechnological transfer activities. The SciFarm Department carrieson national and international research projects granted by WHO,European Commission and industrial partners. The technologicalplatform is based on modern instrumentations including those fordesign and synthetic chemistry (parallel chemistry, microwavechemistry, rapid separation techniques); techniques for biologicalscreening and calorimetric studies (multiplate readers and ITC) andit is integrated with the Centre of Large Instrumentations andCentre for computational studies located in the scientific campusarea.

The main research topics are: computational and experimental drugdesign, combinatorial chemistry, microwave chemistry, librarydesign and chemical biology studies. Natural products studies. Theunit is focused on the discovery, synthesis and rapid screeningtechniques of enzyme inhibitors and protein-protein interference inthe area of anticancer, antiparasitic drugs and beta-lactamase drugresistant infections. In particular ovarian carcinoma is studied within

resistant bacterial infections. The Research products arepublications and 4 patents.

The Lab offers following services: design of new bioactive moleculesthrough experimental and computational techniques, library design,combinatorial chemistry, protein purification and rapid screeningassay. Bioassays set up. In vitro predictive pharmacologyexperimental models. Enzymological screening in GMP.

For more information: http://cdm.unimo.it/home/dipfarm/costi.mariapaola/

Department of Pharmaceutical SciencesResearch centre on Traditional and Innovative PharmaceuticalTechnologies (TEFARTI)Te.Far.T.I. is a university research center which brings togetherresearchers from the university of Modena and Reggio Emilia.Te.Far.T.I. develops multi-disciplinar fields of research (maintaininga broad spectrum of applications) along with the primary focus onpharmaceutical field (Traditional and Innovative PharmaceuticalTechnologies) with interventions and high quality works which adaptthemselves to the market’s requirements.

The researchers belonging to Te.Far.T.I. Modena are managingresearches on the preparation of polymeric and colloidal carriers(microparticles, liposomes, polymeric nanoparticles and solid-lipidnanoparticles) able to target and deliver pharmaceuticals and genematerials to the brain and against tumors. The synthesis of modifiedpolymers and lipids (pegilation, linkage with antibodies or peptidicfragments) used in the preparation of carriers able to selectivelydeliver drugs to the target site and to cross the cellular membrane,is fundamental for the modern drug delivery and for the productionof “smart” innovative delivery systems.

The knowledge developed by Te.Far.T.I. researchers consists of themodification of FDA approved biodegradable polymers, such as poly-lactide-co-glycolide acid, and of the solid-phase synthesis of peptides.The ability of the formulated vectors has been proved by in vivo andin vitro tests with both qualitative and quantitative assays.

The centre offers both experiences on pharmaceutical pre-formulation and formulation and on the use of advancedtechnologies for the chemico-physical characterization of drugs andpharmaceutical products, along with thermal analysis (DSC), highperformance liquid chromatography (HPLC), gas-chromatography,nuclear magnetic resonance (NMR), X-ray crystallography, IR

spectroscopy, microscopic analysis (SEM/ESEM, TEM, AFM,confocal microscopy), dimensional and surface analysis (PCS,ESCA).

The centre has different instruments at customer’s service suchas drying machines for solution (i.e. Spray-drying) or instrumentssuggested by Italian Pharmacopea for the determination and assayson powders (density, absorbent capacity) and solid pharmaceuticalproducts (determination of dissolution, of disaggregation time),along with the more common and used instrumentations for thepreparation of granulates, tablets and capsules.

For more information: www.tefarti.unimo.it

University of BolognaDepartment of Pharmaceutical SciencesGroup of Computational Medicinal ChemistryThe research Group employs several bioinformatic andcomputational methods, which permit the construction and use ofmodels of molecules and molecular complexes of different sizes,from small organic molecules to fully solvated protein complexes inmembrane. Besides basic modeling techniques (based on classicalmechanics or on quantum chemistry), procedures specifically aimedat the design or identification of lead candidates, likepharmacophore building, molecular docking, and virtual screening,are used.

Current activities of the Group concern both the identification ofnew molecules candidate to become pharmaceutical leads, and thestudy of target protein systems. The research lines cover varioustherapeutic fields, like cancer, neurodegenerative diseases(Alzheimer) and neglected diseases (trypanosomiasis), as well asthe drug safety field (drug-induced long QT syndrome). With regardto the identification of possible leads, we are presently consideringsuch molecular targets as BACE1 and Cdk5 (Alzheimer’s disease),Cdk2/Cyclin E and cytochromes P450 19 and 17 (cancer), Faband trypanothione reductase (trypanosomiasis). The molecularsystems currently under investigation are the Cdk7/Cyclin Hcomplex involved in the control of cell cycle and gene transcription,and the cardiac potassium channel hERG, whose blockade is one ofthe most relevant causes of the long QT syndrome in both theinherited and the drug-induced forms.

The Computational Medicinal Chemistry Group is fully available towelcome people from Institutions or Companies, and to train themto the comprehension and utilization of the methods used in thecomputational laboratory. Furthermore, the Group welcomes the

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participation in multidisciplinary projects aimed at the discovery of lead candidates, or at the preclinical development of leads. In thiscontext, expertise and instrumentation can be provided, as well as,through the collaboration of other groups in the Department, thesynthesis of designed single molecules or small libraries of analogs.

For more information: http://www.scfarm.unibo.it/

Department of Electronic, Informatics andSystemic (DEIS)Laboratory of Cellular and Molecular Engineer for the study ofBio-Nano-SystemsThe laboratory research topics focus on the use of cell molecularcomponents in new systems for diagnosis and medical therapy. Thedesign of such system is carried out with a multidiscipline approach,integrating competences from biochemists, biologists, engineersand doctors. The Laboratory was created in 2005 within theCesena Campus thanks to the contribution of three departments ofthe Bologna University (DEIS, ARCES, Biochemistry). The laboratoryis involved in many important research projects, both at nationaland international level, focused on bio-nano technologies, syntheticbiology, pharmacogenetics, tissue engineering.

The Laboratory is equipped to perform experiments of cellular andmolecular biology and computer simulation of biological processesat cellular and molecular scale. Current research activities deal with:biophysics of cellular membranes and systems for the generationof artificial lipidic membranes; bioreactors and engineered tissues;bioinformatics and computational biology; ionic channels and ligand-receptors interactions; prediction of the ternary structure ofproteins and analysis of the molecular dynamics; bio-nanoelectronicdevices; electrophysiology and electrochemistry; epigenetics; geneexpression and signal network; nanopores for clinic applications;molecular sensors based on bio-morph and mixed domaintechnologies; software for cellular and molecular imaging; matrixesof micro-transducers and micro-manipulation; molecular computing;synthesis of genetic programmes for the control of proteinsynthesis and of cellular functions.

The laboratory offers the following services: electrophysiologymeasures on heart cells and neurons for drug screening;experimental evaluation of the drug action on the activity of a singleionic channel and identification of the site of action throughcomputer analysis; analysis of the epigenetic profile regulating thegene expression for genes of physiopathology interest; productionof expression systems for protein generation; design of bioreactorsfor cellular cultures; design and production of process control

systems.For more information:http://www.ing2.unibo.it/Ingegneria+Cesena/Facolta/Strutture+di+servizio/Laboratori/Cesena/ICM/default.htm

UNIVERSITÀ DEGLI STUDI DI PARMAIndustrial Engineering DepartmentApplied mechanic groupThe research group aims at research and implementations aboutautomated machines design, motion control and tribology, inparticular in the fields of pharmaceutical and food industry.

Experimental activities make use of some test-beds designed forinvestigations on sustainability issues: contaminants sealingsystems and methods, friction reduction, reducing residualvibration. Moreover, new software tools have been written formechanism synthesis with advanced laws of motion, for simulationwith multi-body analysis of mechanical systems including large scaleproblems, like granular flows.

Ongoing agreements with industries are aimed at implementingnew technologies for sterilizing containers for low acid cannedfoods, building an innovative automated factory for manufacturingmedical devices where new autonomous guided vehicles will beused. Some researches are active members of the Italian GAMPforum and strictly cooperate with the main world pharmaceuticalequipment manufacturers.

The department houses a postgraduate course on design andvalidation of automated machines for life sciences industries. Theresearch group is willing to start collaborations and agreementsaimed at transferring its know-how on pharmaceuticalmanufacturing technologies. Moreover, it is possible to agreeresearch programs for designing bespoke machine prototypes andfor redesign existing machines taking in account energy saving andenvironmental sustainability issues as newer standards and energycosts require.

For more information: http://ied.unipr.it/silve

Pharmaceutical DepartmentPharmaceutical Chemistry GroupThe group includes several full-time researchers and a varyingnumber of graduated and post-doc students, working in the field of

medicinal chemistry to the discovery and development of newcompounds having potential therapeutic applications. The group isdivided into three units, fully coordinated, dedicated to synthetic, bio-analytical and computational chemistry, respectively.

The research in the drug design and discovery area allowed theidentification of new compounds with promising biologicalproperties. In particular, a new class of endocannabinoid tonemodulators, have been discovered with the contribution of thegroup, and a new compound has been advanced to clinical studyfor the treatment of anxiety and depression; the medicinal chemistryinvestigations also resulted in the characterization of new histamineH3 antagonists, melatonin receptor ligands and EGFR inhibitors,potentially useful for the treatment of obesity, sleep disorders andcancer, respectively. The group is also involved in projects at thedevelopment stage, studying drug stability, pharmacokinetics andmetabolism; optimization of these features by structure-activity andstructure-property relationship analysis have been actively pursued.

Design and synthesis of new compounds devised as enzymeinhibitors or receptor ligands. Purity samples for chemicalsubstances (NMR, HPLC, elemental analysis: C, H, N, S).

Chemoinformatics and computational chemistry: design andanalysis of compound libraries; estimation of physicochemicalproperties; virtual screening.

Drug metabolism and pharmacokinetics: in vitro evaluation ofcompound metabolism (plasma, liver extracts); quantification ofdrug and metabolite levels in vivo after systemic administration (LC-UV, LC-MS). Detection and measurement of drug-protein adducts(MALDI-TOF).

For more information: www.unipr.it/arpa/dipfarm/medchem

Pharmaceutical DepartmentPharmaceutical Technologies GroupThe group is composed by a number of permanent personnel andhost several PhD, post-doc, fellows students, including Italian andInternational students. The group is focused on the discovery anddevelopment of new technique, products and drug deliveryplatforms.

Group activities include drug delivery studies for administrationsalternative to the parenteral rout, especially the pulmonary, nasal,trans-dermal and oral routes.

In the last few years the group has registered several internationalpatents, all of them licensed to Regional and extra-RegionalPharmaceutical industries.

The group offers the following services: design and development ofdrug delivery systems prototypes; validation of drug manufacturingprocedures; laboratories dedicated to the development of inhalingtherapy and trans-dermal preparations.

For more information: www.unipr.it/arpa/dipfarm

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