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Paolo Barbanti The Italian pharmaceutical industry: trends and business opportunities © 1
Via Placido Riccardi 19 20132 Milano Italy Tel. ++39-02-45409122 / 27203492 Fax ++39-02-27203492
The Italian Pharmaceutical Industry
Table of Contents
1. OVERVIEW 3
1.1 Bulk Drugs and Pharmaceuticals Products 3
1.2 Production 3
1.3 Italian Imports 3
1.4 Italian Exports 5
1.5 Types of Packages Prevailing in Italy 5
1.6 Pharmaceuticals in Liquid Form 6
1.7 Pharmaceuticals in Solid Form 6
1.8 Various Pharmaceutical Products 7
1.9 Trends and Demographics 7
Paolo Barbanti The Italian pharmaceutical industry: trends and business opportunities © 2
1.10 Medicines in demand 8
1.11 Dealing with Demographics 9
1.12 Implications for Research 9
1.13 Distribution 11
1.14 Market Structure 11
1.15 New price-setting Models 13
1.16 Changes in Distribution Margins 14
1.17 The Introduction of Generics 14
1.18 Attempts to influence General Practitioner Prescribing 15
2. A SELECTED TARGET OF ITALIAN COMPANIES 17
2.1 Alfa Wassermann 17
2.2 Bouty 25
2.3 Chiesi Farmaceitci 36
2.4 Dompé 41
2.5 Menarini 53
2.6 Recordati 58
2.7 Sigma Tau 68
Paolo Barbanti The Italian pharmaceutical industry: trends and business opportunities © 3
Overview
Bulk Drugs and Pharmaceutical Products
Production
Italian pharmaceutical sector produces pharmaceutical products and medicine worth 17.6 billion
Euros, and is an important segment in the Italian economy. In recent years, Italian pharmaceuticals
industry has shown a positive trend in development. The average annual growth has been around 5-
6%.
Consumption: Italian consumption of pharmaceutical products is estimated to be about 6.5 billion
Euros (2003).
Most major international pharmaceutical companies have a hold in Italy. These include Roche,
GSK, Pfizer, Novartis, Bayer, Sanofi-Aventis, Lilly etc. They also dominate the Italian
pharmaceutical industry and control about 60 to 65% of the total pharmaceutical trade. While there
are a large number of Italian companies in the pharmaceutical sector, they are relatively small
compared to these multinationals. Italy does not have any homebred large multinational
pharmaceutical company, which could be matched up to the multinationals of USA, Germany,
Switzerland or UK.
Italian Imports
Italian imports include products such as: Acyclic alcohols, Cyclic alcohols, Ethers-peroxide,
Ketone, Quinine, Carboxylic acids, Amino-alcohols, Carboxyamide, Nitrile, Heterocyclic
compounds, Pro-vitamin, Vegetable alkaloids, Antibiotics, Glands, Antis era, Vaccines,
Medicaments, Penicillin and Streptomycin etc.
Details regarding the figures of the Italian import of the last three years are given below:
YEAR Value in Euro (million)
2002 10279.6 2003 10768.8 2004 11349.0
Paolo Barbanti The Italian pharmaceutical industry: trends and business opportunities © 4
Analyzing the aforementioned figures, it is noticeable, that there has been an increasing trend in
Italian import concerning the said period of time. While in the year of 2002, the Italian import was
worth 10,279.6 million Euros, it increased to 1,349.0 million Euros in 2004. Italian import in 2003
exceeded the import of 2002 by 4.76%, and the import of 2004 exceeded that of 2003 by 5.39%.
About 62% of the total products are imported into Italy are from Switzerland, Germany, U.K,
France and Belgium
Details regarding the import of pharmaceutical products coming from key countries are given
below:
Key Countries Exporting to Italy (2004)
Country 2003 Value in Euro (million)
2004 Value in Euro
(million)
Total Imports 10768.8 11349.0 Switzerland 1727 2079 Germany 1278 1383
United Kingdom 1515 1110 France 1220 1302 U.S.A. 1098 1180
Belgium 821 875
Ireland 1036 988 Netherlands 690 884
Sweden 247 256 Spain 188 265 China 116 114
Denmark 134 145 Austria 38 39
Israel 135 206 Australia 16 13
India 18 14
Market Share in Italian Imports: (Year 2004)
Country Market share in Italian Imports
Switzerland 18.3 Germany 12.9
United Kingdom 9.7 France 11.4 U.S.A. 10.4
Belgium 7.7 Ireland 8.7
Paolo Barbanti The Italian pharmaceutical industry: trends and business opportunities © 5
Netherlands 7.7
Sweden 2.2 Spain 2.3 China 1.0
Denmark 1.2 Austria 0.3 Israel 1.8
Australia 0.1 India 0.1
Italian Export
Details of Italian Export of Drugs and Pharmaceuticals are given below:
YEAR Value in Euro (million)
2002 10139.6 2003 9740.9 2004 9525.3
During 2003, Italian export decreased by 3.9% comparing to that of 2002. In the year 2004, it was
registered that a decrease of 2.2% in Italian export comparing to that of 2003, took place.
Italian pharmaceutical products are mainly exported to Belgium, Germany, U.K. Switzerland and
USA. They constitute about 60% of the total Italian export of these products.
Types of packages prevailing in Italy
For the pharmaceutical industry, the primary function of packaging remains mainly that of
protecting the product and making it easy and functional to use. To give a clearer picture of the
trends regarding the various types of packaging, some forms are provided below to give the general
idea.
Paolo Barbanti The Italian pharmaceutical industry: trends and business opportunities © 6
Pharmaceuticals in liquid form
The area of medicines in liquid form includes those taken orally, by injection, as well as ophthalmic
and otological products. The packaging used, therefore, comprises vials and bottles of various sizes.
Of oral liquid products, 30.7% are packed in small or large plastic bottles; 27.4% are packed in
glass objects either glassware containers or glass tubes, and 41.9% are in glass bottles.
Current trends are towards a growth in the use of plastics bottles for syrups, whereas when small
glass bottles are concerned, more container glass is being used, to the detriment of glass tubes.
Where injectable medicines are concerned, the packaging still consists of vials in glass tubes or
small bottles in glass tubes or glass containers. There is a trend in the market towards the use of
freeze-dried products with a consequent increase in the number of small bottles, which obviously
creates a need for vials for sterile water. About 47% of the market is made up of packaging using
vials only, while, approximately 53% of the packaging consists of both vials and small bottles. The
vials are made of glass tube, while the small bottles are both packed in glass containers and glass
tubes.
Regarding liquid pharmaceuticals not taken orally (ophthalmic and ontological products, etc.) there
is a marked trend towards using plastic bottles which account for 94.4% of the entire market, and
small glass bottles account for 5.6% only.
Pharmaceuticals in Solid Form
Approximately 93% of the packaging for solid medicines to be taken orally (tablets, capsules and
soluble powder) is in the form of blister packs. Other important types of packaging are: small
bottles, plastic tubes and bags in bonded materials (paper-aluminum-PE), which have a 4% share of
the entire market. The remaining 3% is made up of rigid aluminium tubes, small glass bottles and
strips of bonded material (card-aluminium-PE).
With regard to powder products for external use, 56.2% of the packaging used is rigid aluminium
tubes, and the remaining 43.8% packages are available in rigid plastic tubes (this field is currently
on the increase).
Products for rectal or vaginal use, depending on their pharmaceutical specialty, are usually in cell-
packs or push-through packs. Plastic materials and thin aluminium foil are also found in this type of
packaging.
Paolo Barbanti The Italian pharmaceutical industry: trends and business opportunities © 7
Various Pharmaceutical Products
As for creams, gels, etc., about 92.5% of the products are packed in flexible tubes (specifically,
68.5% in aluminium and 24% in bonded material, namely, plastic-aluminium. There seems to be a
slight trend towards the plastic-aluminium option. The remaining 7.5% of this type of
pharmaceutical product is packed in sachets of bonded material (card-aluminium-PE).
The packaging used for spray products is plastic bottles fitted with mechanical dispensers (21.7%)
or the classic metal aerosol (78.3%). The trend towards aerosols, in aluminium or tinned strip, is on
the increase.
Comments and Market Situation:
• Italian pharmaceutical sector manufactures products that worth 17.6 billion Euros and the
average annual growth rate is around 5-6%.
• Most major international pharmaceutical companies like Roche, GSK, Pfizer, Novartis,
Bayer, Sanofi-Aventis, Lilly etc. have a hold in Italy and they control about 65% of the total
pharmaceutical trade in Italy.
• Italy imports bulk drugs and pharmaceutical products that worth 10.2 billion Euros. Around
62% of the total import which enters Italy comes from Germany, Switzerland, France, U.K.
and Belgium (2003).
• Italy exports bulk drugs and Pharmaceutical products the worth of which is 10.1 billion
Euros. About 60% of the total Italian export is mainly sent to Belgium, Germany, U.K.
Switzerland and USA (2003).
• The Italian market of pharmaceuticals is determined by products supplied by large Italian
and foreign multinationals. The foreign multinationals have their own distribution networks
with specialised sale outlets for marketing products at the level of pharmacies, hospitals,
health insurance companies etc. The Italian pharmaceutical industries have similar
distribution networks for the purpose of expanding their sales.
Paolo Barbanti The Italian pharmaceutical industry: trends and business opportunities © 8
Trends and demographics
In terms of value, Italy’s pharmaceutical market is the fourth largest in Europe and represents
around 13% of the regional total. The continuing demand for pharmaceuticals has put pressure on
the government’s overall funding of healthcare, which stands at around 9% of Gross Domestic
Product (GDP). As has been observed in many other countries, the growth in pharmaceutical
spending has begun to outstrip the growth in total healthcare spending.
Medicines in demand
As a percentage of the total healthcare spending, the current expenditure on pharmaceuticals in Italy
stands at around 22%, which is higher than that of France and Germany – and even the USA.
However, such figures must be examined carefully because although new medicines contribute to
healthcare spending increases in the short term, they can result in net healthcare savings on the long
run because of reduced hospitalization rates, as well as reduced mortality and morbidity.
Globally speaking, Italy is ranked sixth with respect to annual pharmaceutical spending per person
in terms of purchasing power parity (PPP).
Given below are the top six rankings:
Country Pharma-products spending/Person
(EURO per annum)
1. USA 1302 2. JAPAN 568
3. FRANCE 456 4. GERMANY 409
5. UK 365 6. ITALY 304
Pharma-products spending / Person
Products that are in the cardiovascular, alimentary/metabolism, central nervous system, respiratory
and anti-infective therapeutic classes, represent the majority of sales in the Italian pharmaceutical
Paolo Barbanti The Italian pharmaceutical industry: trends and business opportunities © 9
market. During 2005, these categories represented around 70% of the total pharmaceutical sales in
Italy, which was interestingly paralleled to the distribution pattern in the USA, the leading global
market. There is also a recent rise in sales of dermatology, analgesic, ophthalmology, as well as
cough and anti-influenza products.
Dealing with Demographics
Demographic factors will have a major impact on the make-up of the Italian pharmaceutical market
in the future. Although ageing of the population is affecting healthcare policy in most countries, it is
particularly relevant to Italy since the country may have one of the ‘oldest populations’ in the world
by 2050. This is a result of the fact that the country might have the highest percentage in the world
of population aged 65 and over (18.1%), and the lowest percentage of population aged 15 and
below (14.1%).
This scenario presents the pharmaceutical industry with both opportunities and challenges. On one
hand there will be increased demand for medicines aimed to tackle conditions that predominantly
affect the elderly and this will benefit companies carrying out R&D in these fields. However, in
view of several economic studies that have analyzed the effect of population ageing on healthcare
spending, the government is likely to expand its cost containment approach to healthcare.
It is the changing nature of the demand for healthcare that has prompted the Italian authorities to
develop a more proactive approach to its policies. The recent Italian Sanitary Program (Piano
Sanitario Nazionale) has placed a greater emphasis on preventative measures in healthcare. This
involves preparing a plan for educating people in order to make them understand that changes in
their lifestyle may help them avoid serious medical conditions in the future.
However, the success of such initiatives depends on the government’s ability to have a good
communication with the public together with involving those who provide their healthcare.
Paolo Barbanti The Italian pharmaceutical industry: trends and business opportunities © 10
Implications for Research
The leading pharmaceutical markets are also major fields for R&D, and Italy is no exception in this
matter. The country is ranked fourth in the world in terms of life sciences R&D spending, and has a
well-organized network of academic and private institutions which are engaged in research projects.
As a result of Italy’s National Health Plan, which focuses on certain priority disease fields, over 250
research projects have been approved so far and these are valued at over 60 million Euros.
Selected Priority Research Areas
� Cardiovascular diseases
� Oncology
� Infectious diseases
� Neurodegenerative conditions
� Immune system disorders
� Molecular medicine and genetic diseases
Italy’s emphasis on an industrial application of this medical research provides an incentive for the
involvement of a large range of pharmaceutical and biotech companies. Italy is already an important
location for clinical trials, with about 600 studies being carried out each year in a variety of
therapeutic areas, and its popularity is likely to increase. In particular, as the target population for
new medicines in future therapeutic areas will often be the elderly, clinical trials will need to reflect
this important part of the population. At present, there are a number of reports that highlight how
the elderly remain under-represented in clinical trials. Thus, the profile of Italy’s population makes
the country an ideal location for clinical trials as for improving this situation. However, much will
depend on the industry’s abilities to communicate with the local medical community and patients to
encourage their involvement in these types of clinical trials. Italy represents an attractive market for
Paolo Barbanti The Italian pharmaceutical industry: trends and business opportunities © 11
the pharmaceutical industry, because despite the government’s efforts to slow healthcare spending
by targeting pharmaceuticals, there will inevitably be an increase in the demand for new medicines.
The pharmaceutical industry’s challenge is how best to show that use of their products will help
Italy meet its healthcare targets in the long term. The country also represents a vibrant environment
for industry research but this will require companies to demonstrate to the medical community and
patients that their projects have relevance to the healthcare needs of the population.
Distribution
Market Structure
Italy’s NHS allows both private and public pharmacies to coexist. Private pharmacies are owned by
pharmacists who function as independent contractors under the NHS. Public ones, mainly
municipal, are managed by pharmacists employed by the municipality in which the pharmacy is
located. Despite this administrative division, both types of pharmacies are licensed to sell
commercial products and, on behalf of the local health unit, pharmaceuticals. Commercial goods
mainly include bandages, contraceptives, items for personal hygiene, baby products (such as diapers
and infant formula) and cosmetics (some pharmacies also sell homeopathic products).
Pharmaceuticals include drugs and dietary goods and can only be sold if a consumer has a
prescription from a general practitioner.
All the revenue goes directly to the owner of the pharmacy: to the pharmacist if the pharmacy is
private, and to the municipality if the pharmacy is municipal, which then pays a salary to the
pharmacist running the pharmacy.
Pharmacies’ revenue is a percentage, set by law (usually the Finance Act) of the overall price before
VAT: the most recent rate, set in 1996, is 26.7%. This rate does not take into account special
Paolo Barbanti The Italian pharmaceutical industry: trends and business opportunities © 12
discounts that pharmacies might be able to negotiate with manufacturers. Conversely, local health
units are responsible for reimbursement.
• Pharmacies cater to 86.4% of the total Italian demand; there are 16,642 pharmacies in Italy
and 252 wholesalers.
• Hospitals cater to the balance 13.6 % of the total Italian demand.
The turning-point for Italy’s pharmaceutical sector was 1, January 1994, when Law 537/1993 came
into force. The pressure to contain expenditure and an impressive series of scandals favoured the
most radical change ever in Italy’s pharmaceutical policy. Since 1994, regulatory policies have:
• redefined the positive list;
• implemented a nationwide drug expenditure budget;
• created new price-setting models;
• changed distribution margins;
• introduced generics; and
• attempted to influence the prescribing of general
practitioners.
In 1994, the National Committee for Pharmaceuticals was established. The 1978 positive list was
abolished, and drugs were reclassified into four groups:
• group A: drugs for severe and chronic illness
• group B: drugs of therapeutic importance not included in
group A
• group C: drugs not included in groups A and B
• group H: drugs provided only by hospitals.
Paolo Barbanti The Italian pharmaceutical industry: trends and business opportunities © 13
Cost-sharing rules were also modified in 1994: for pharmaceuticals in group A, patients pay 1.55
Euro if the prescription includes only one item or 3.10 Euros for more than one item; and for
pharmaceuticals in group B, patients pay only 50% of the price. Consumers pay the whole cost for
pharmaceuticals in group C, which are not covered by the NHS.
The new list was established according to four criteria: 1) clinical efficacy, documented by
evidence-based criteria; 2) risk-benefit balance of the therapy; 3) acceptability of the therapy to
patients; and 4) cost of the therapy.
The National Committee for Pharmaceuticals also introduced caveats for some drugs; these can be
considered guidelines for the use of pharmaceuticals.
New price-setting Models
Pharmacists freely determine the prices of commercial goods; prices for each pharmaceutical
product are fixed centrally through a negotiation process involving the National Committee for
Pharmaceuticals and the representatives of the major pharmaceutical companies. In 1994, the price-
setting system for drugs was modified. The Committee on Pharmaceuticals (CIP Farmaci), the body
charged with regulating drug prices, was abolished, and a year later the Interdepartmental
Committee on Economic Planning (CIPE) announced a new method for determining drug prices
based on cost estimates derived mainly from information from private companies that effectively
replaced the previous one. According to the new system, prices can be freely set without exceeding
the average European price. The average European price was based on the five most sold drugs,
including generics. Only France, Germany, Spain and the United Kingdom were taken into
consideration in deriving the average European price. Foreign prices were converted into Italian
currency based on purchasing power parity (PPP), a price index used for international comparative
studies.
The principle of similarity was adopted to identify the European equivalents of Italian products: the
same active ingredient, the same route of administration, the same or therapeutically comparable
pharmaceutical form and a similar dosage.
Paolo Barbanti The Italian pharmaceutical industry: trends and business opportunities © 14
The pharmaceutical industry criticized the new model: in particular, restricting the comparison to
only four countries, including generics in calculating the average European price and using PPP. As
a result of the industry’s dissatisfaction, the Interdepartmental Committee on Economic Planning
(CIPE) introduced a sort of reference price in 1996, based on the principle of the same prices for the
same drugs. The basic idea is that products in group A and group B that use the same active
ingredient, have the same method of administration and have the same or a comparable
pharmaceutical form should have the same prices per unit of compound. This pricing mechanism
exists only for products in groups A and B, since the prices for group C pharmaceuticals are freely
established by the private sector.
Further, in 1997, the Interdepartmental Committee on Economic Planning defined a new price
system for innovative drugs authorized by the European Agency for the Evaluation of Medicinal
Products. Prices are set by negotiation between the National Committee for Pharmaceuticals and
private companies, using the following criteria: a) cost–effectiveness; b) foreign prices; c) internal
market forecasts; and d) investment made by the company related to the introduction of a new drug.
Since July 1998, the average European price method (used for non-innovative drugs) has been
modified to include all European countries and current exchange rates.
Changes in Distribution Margins
Controlling public pharmaceutical expenditure also required focusing on pharmacies. Wholesale
and pharmacy margins were traditionally set as a fixed markup on ex-factory prices and have not
varied much during the last 15 years. From 1981 to 1997 the wholesale margin has changed from
8.0% to 6.65% and the pharmacy margin of drug prices excluding VAT from 25.0% to 26.7%
In 1992, a fixed compulsory rebate on pharmacy margins was introduced for products covered by
the NHS. The rebate was initially set as a fixed proportion of the price (2.5% of the price excluding
VAT, and 3% since 1995).
From 1997, pharmacists were forced to apply a discount to products covered by the NHS. Different
discount rates apply to different price ranges to make the pharmacy’s margin regressive (decreasing
with the price). The discount was 3.75% for prices less than 25.8 Euros; 6% for those between 25.8
Paolo Barbanti The Italian pharmaceutical industry: trends and business opportunities © 15
Euro and 51.6 Euros; 9% for those between 51.6 Euros and 103.3 Euros; and 12.5% for prices equal
to 103.3 Euros or bigger than that.
The Introduction of Generics
Despite all the interest in cost containment, Italy’s authorities have not given generic drugs much
attention. As a consequence, their use is very limited. The 1995 Finance Act introduced the term
generic into legislation. The law provides pricing incentives to promote generics, stating that, if the
product is marketed at a price at least 20% lower than the equivalent speciality, it is automatically
listed in the same co-payment group. Other incentives come from the financial accountability of
regions over health care and the consequent process of management improvement and cost
containment in the local health authorities of the NHS.
Because wholesale and pharmacy margins were traditionally set as fixed mark-ups, this has made
the distribution of expensive drugs more profitable. Since 1997, the pharmacy margin on NHS-
covered products, became inversely related to the product’s price.
However, the regressive effect is still very slight and does not favour the use of generics. As a
matter of fact, the generics market in Italy is still negligible. The latest data show that generics
account for only 3% of all prescribed medicine units which are sold. However, recently as regional
acts passed (Tuscany being one of the most active regions), the aim is now to promote the
prescription of generics by distributing lists of generics among general practitioners and to
encourage them to prescribe generics. These reforms are nevertheless still in their early stages, and
nationwide implementation is far from being accomplished.
Attempts to influence General Practitioner Prescribing
The prescriptions of general practitioners have never been strictly controlled. Only after the series
of scandals affecting the whole pharmaceutical system, the 1992 reform of the NHS created greater
incentives and opportunities for making general practitioners accountable for their prescribing
activities, such as an expenditure budget for each general practitioner and incentives for general
practitioners to achieve this target. The specific impact of each new regulatory measure is difficult
to assess, even though the reclassification of drugs by the National Committee for Pharmaceuticals
substantially affected NHS drug expenditure. In particular, since 1993, the measures described
Paolo Barbanti The Italian pharmaceutical industry: trends and business opportunities © 16
above have had two main effects. Firstly, they dramatically reduced NHS pharmaceutical
expenditure from 1993 to 1995. The introduction of guidelines from the National Committee for
Pharmaceuticals and the introduction of a nationwide drug expenditure budget largely achieved this
aim. Secondly, much of the reduction in NHS pharmaceutical expenditure resulted by shifting costs
from the public sector to the patients. The demand for drugs is steep: despite an increase in the
prices of drugs in group C, consumption has increased.
Nevertheless, these cost-containment strategies were not long-run manoeuvres but just emergency
measures to stop the never-ending increase of drug expenditure. This could explain why
expenditure increased again rapidly from 1996 to 1999.
Paolo Barbanti The Italian pharmaceutical industry: trends and business opportunities © 17
A selected target of Italian Companies
ALFA WASSERMANN
A concrete and successful strategy based on commitment to research and development, production
using the modern technologies and an industrial mentality oriented towards internationalization - all
this has enabled Alfa Wassermann to occupy an important place in the international pharmaceutical
business. This is the strategy at the heart of the company's continued development and the success
of its products in various areas. In the prescription pharmaceuticals, Normix® is without doubt the
product which has given the greatest satisfaction. This antibiotic, indicated for the treatment of a
wide range of gastroenteric disorders, is not just a market leader in Italy, but has also been
recognised by the FDA and approved for sale in the USA under the brand name Xifaxan ™.
For the non prescription specialities, Alfa Wassermann can boast Neoborocillina ®, a historic brand
known to all Italian families.
Alfa Wassermann, Inc. is the worldwide leader in the technology of ultra – centrifugation. Its
equipment is used by all the major vaccine manufacturers.
Research has become a keystone in Alfa Wassermann's corporate strategy, responding to the
constant demand for innovation. The result has been pharmaceutical products of great importance
for the growth of the group.
Particularly significant is the success of Sulodexide (Vessel®), a heparinoid with an anti-thrombotic
and profibrinolytic action, and Parnaparin (Fluxum®), a low molecular weight heparin for
prophylaxis and treatment of venous thromboembolism But the most prestigious result of Alfa
Wassermann's research is Rifaximin (Normix®), a topical intestinal antibiotic.
Leader on the Italian market and registered in a number of countries throughout the world,
Paolo Barbanti The Italian pharmaceutical industry: trends and business opportunities © 18
Rifaximin has also been launched on the USA market after having obtained FDA approval, the
maximum recognition for a drug developed through Italian research.
Salix Pharmaceuticals Inc., the US company responsible for selling Rifaximin under the name
Xifaxan™, is quoted on the American Nasdaq. The Manufacturing Division of Alfa Wassermann is
based in Alanno (Pescara). The modern production and packing plant is equipped with the most
avant-garde technology to guarantee production processes at the highest possible levels covering the
needs of the company and its licensees, the Alanno plant also has a long tradition of contract
manufacturing for third parties.
The Alanno factory is authorised for production by the Italian Ministry of Health and monitored by
regular inspections certifying total compliance with cGMP standards.
In the spirit of and in compliance with this certification, the Quality Control laboratories carry out
regular validation of all the analytical methods used to analyse primary materials and intermediate
and finished products. The Alfa Wassermann production unit at Alanno covers a surface area of
100,000 m² with a covered area of 17,000 m² divided into 11 departments in seven blocks of
buildings. It produces 30 million items per year for Alfa Wassermann and other Italian and
international pharmaceutical companies.
Alfa Wassermann S.p.A. was founded in 1948 and is a consolidated presence on the Italian
pharmaceuticals market, researching, producing and selling both prescription and self-medication
specialities. The headquarters and research laboratories are located at the original premises in
Bologna, while there is a modern production unit at Alanno (Pescara). The International and
Diagnostic Divisions are based in Milan.
Alfa Wassermann SpA promotes its products by means of a network of representatives who visit
general practitioners, specialists and pharmacists as well as public and private laboratories. With a
workforce of over 650 people, the company also acts as a holding company for the group.
One of the strong points of Alfa Wassermann SpA is that more than 60% of turnover is generated
by its own products, developed by in-house research. These include market leaders such as
Normix®, an innovative antibiotic with a topical intestinal activity, discovered and patented by Alfa
Wassermann. Other important specialities are Alfaferone® (Alfa natural interferon) and Fluxum®
Paolo Barbanti The Italian pharmaceutical industry: trends and business opportunities © 19
(Parnaparin - patented low molecular weight heparin). Alfa Wassermann has also a Division
marketing and selling non prescription specialities with an extensive network of direct promoters to
pharmacies.
The Division owns a wide range of products acknowledged as efficacious and is a market leader in
the oral disinfectant segment with the widely known and appreciated Neoborocillina®. Alfa
Wassermann is also present in the human in vitro diagnostic sector. The Diagnostics Division sells
a wide range of systems and reagents and also distributes the products of leading Japanese and
American manufacturers in Italy.
In 1989, Alfa Wassermann set its own International Division with two main aims - to increase
exports of its speciality drugs by exploring new territories and to promote the international
development of its original products with a network of strategic alliances. Today Alfa Wassermann
operates with a portfolio of 11 products in more than 60 countries throughout the world and an
efficient network of distributors, efficiently backed by an in-house organisation able to provide all
the assistance required. Normix® (Rifaximin) is one of the main products abroad and has
significant growth prospects.
The product internationalization plan is starting to give results. At present, Rifaximin is registered
in 12 countries and in October 2004 the product, under the name Spiraxin®, was introduced into the
market in Spain by Bama-Geve S.L. and another Alfa Wassermann licensee company. But the most
important goal was, without doubt, the launch of the drug on the USA market under the name
Xifaxan™. The results obtained by the International Division include the setting up of Euro
Alliance, a cooperation agreement with other European pharmaceutical companies for research and
development of new drugs.
For more than thirty years, Alfa Wassermann, Inc. instruments and products have been used in
analysis laboratories all over the world for a wide range of diagnostic applications.
These instruments are designed and produced with the aid of the most advanced technology,
guaranteeing the accuracy of the laboratories' analyses.
Currently Alfa Wassermann, Inc. supplies hospital and private analysis laboratories and veterinary
clinics with a line of clinical chemical analysers (ACE Alera) offering a high degree of automation
and reliability.
Paolo Barbanti The Italian pharmaceutical industry: trends and business opportunities © 20
Alfa Wassermann, Inc. is also leader in separation technology with a line of ultra-centrifuge
equipment used by leading producers of influenza vaccine throughout the world and in other
industrial and research applications. On the basis of its know-how in ultra-centrifuge technology,
Alfa Wassermann, Inc. is designing an innovative instrument which will enable research
laboratories to take great strides forward in the study of proteins and their interaction at a cellular
level.
The production facility is located at West Caldwell (New Jersey-USA) and international sales are
coordinated by the associate company Alfa Wassermann B.V. based in the Netherlands, with a vast
network of distributors.
The globalization of the markets is also affecting strongly the pharmaceutical business. Since the
beginning of the new millennium, Alfa Wassermann reacted to this trend by supplementing its
traditional export activities with a drive to establish its own organization in a number of markets.
This goal has been pursued by the acquisition of local companies or by setting up new subsidiaries.
The new subsidiaries include Alfa Wassermann Polska sp.z o.o., Alfa Wassermann Tunisie s.a.r.l
and Alfa Wassermann (Beijing)Market Research & Management Company Ltd. These are not, of
course, random decisions, but selecting countries whose markets have interesting growth
opportunities.
Acquisitions include the Spanish company Bama-Geve S.L. and the Portuguese BioSaùde- Produtos
Farmacêuticos, Lda., both operating on the Iberian peninsula. BioSaùde is a relatively young
company standing out for its rapid growth, while Bama-Geve is a company with a long tradition on
the Spanish market. Founded in 1909, it has specialized in three areas, dermatology, cardiology and
the hospitals market, with established products such as the historic Linitul® (medicated gauze) and
the more recent Mepentol®, an innovative product for the prevention and treatment of bed sores.
Bama-Geve also sells Alfa Wassermann products such as Tonocaltin®, indicated for the treatment
of osteoporosis and the well-known Rifaximin, which is also becoming established on the Spanish
market under the name Spiraxin®.
Paolo Barbanti The Italian pharmaceutical industry: trends and business opportunities © 21
At the beginning of 2004, Alfa Wasserman acquired a 35% stake in this company. Farmigea,
founded in 1946, is a pharmaceutical company based in Pisa and specialized in Ophthalmology and
Gynecology. The company manages and oversees all the various steps involved in the manufacture
of its products: from research to production, from providing scientific information to physicians to
marketing and distribution. The manufacturing process now is carried out in a new and state-of-the-
art plant. Farmigea and Alfa Wassermann made the same choice to put Research & Development at
the top of their business strategies and therefore innovative products are being developed
continuously.
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Paolo Barbanti The Italian pharmaceutical industry: trends and business opportunities © 23
Paolo Barbanti The Italian pharmaceutical industry: trends and business opportunities © 24
Offices and Plants
Alfa Wassermann S.p.A. - Bologna
The "historic" headquarters of Alfa Wassermann are situated in Bologna. Where the Head
Offices, the Research Laboratories and two Divisions:
- the Pharma Division
- the OTC Division
are located too.
Alfa Wassermann S.p.A. Milano
Two Divisions:
- the International Division
- the Diagnostics Division.
Alfa Wassermann S.p.A. - Alanno
The Alanno plant, recently expanded and renovated according to the latest standards, has a
constructed area of over 16,000 sqm divided into 11 sections distributed over 7 blocks.
The warehouse can store up to 3,000 pallets and is equipped with an air-conditioning system
capable of ensuring an even temperature.
Paolo Barbanti The Italian pharmaceutical industry: trends and business opportunities © 25
BOUTY
Bouty has a strong hold in the Self Care (OTC) with different product dosage forms such as
sedatives, eye drops, analgesics and others; Wound Care - a complete range which differs from the
competitors for the presence of the most innovative haemostatic range on the market; Oral Care –
denture cleaners and adhesives and range of mouthwashes and toothpastes; Home Diagnostics –
early pregnancy and ovulation tests, and Cosmeceutical – products classified as cosmetic and at the
same time considered to have important attention to the curative functions.
Bouty as a reliable distributor, can provide manufacturers without an adequate Italian sales network,
or one of sufficient size, complete Italian market coverage. Bouty boasts of having a professional,
effective sales force in the pharmacy and mass market channels that can function as the
manufacturer's sales and marketing organization.
Products
ALLERGAN – dermatological cream
ASATEX HAIR CARE -anti-hair loss treatment
ASPARTINA – table sweetener
BABY ZANZARA - biological anti mosquitos
products
CALMINE – analgesic
CEROXMED - medication and bandage range
Paolo Barbanti The Italian pharmaceutical industry: trends and business opportunities © 26
CERULISINA - otological solution
CERULISINA FAST- otological spray
CONFIDELLE PROGRESS – pregnancy and
ovulation test
DAIGO- mineral supplement
DAIGO ENERGY - energy bar
DAIGO MAG- magnesium supplement
DAIGO PROTEIN - proteic bar
DAIGO SPORT - energetic supplement with
mineral and antioxidant vitamins C and E
DEOPED – foot care products
GRAN VISTA – reading glasses
NEO-EMOCICATROL – oinment
NOCTIS - supplement
OCTILIA – eyewash
ODONTOVAX – dental prevention and treatment
ORASIV – denture care products
Paolo Barbanti The Italian pharmaceutical industry: trends and business opportunities © 27
PEARL DROPS – Whitening toothpastes
PEARL DROPS SMOKERS - 3 in 1 mouthwash
PERILLACTIVE - cream dry and atopic skin
PROPOCAINA - propocitral products
RELAXAR – oinment
SINEGAS – a natural remedy for intestinal gas
VAXITIOL 2 – biological lactobacillus
supplement
VAXITIOL COMB - probiotic + prebiotic
supplement
VERELAIT - laxative
Mass Market
CARE FOR YOU - daily hygiene products for all the family
CEROX EMOSTATICO - medication and bandage range
Paolo Barbanti The Italian pharmaceutical industry: trends and business opportunities © 28
CEROX ATHLETIC - products for prevention and treatment of home and
sports small accidents
CEROX AROMATHERAPIA - essential oils plasters
CEROX BALSAMICO - essential oils plaster
CEROX PROTECTION- essential oil patch
FIRST RESPONSE - pregnancy and ovulation test
MUDD – clay cleansing masks
PEARL DROPS – Whitening toothpastes
PEARL DROPS OZONE - self cleaning toothbrushes
RIGIDENT - complete range for denture
THERMAE - thermal products range
Drug Delivery of Advanced Technologies
The Drug Delivery System division, through the adoption of modern technologies, develops and
produces different kinds of products:
Trandsermal patches: Transdermal patch technology us away a way in which drugs are released
constantly. Transdermal patches help reducing collateral effects and increase patients’ tolerability of
drugs. The active principle is absorbed gradually, as it acts locally (in the case of topical patches) or
enters body circulation directly (in the case of Transdermal patches with systemic action).
Paolo Barbanti The Italian pharmaceutical industry: trends and business opportunities © 29
Transdermal Drug Delivery System technology has a wide range of applications: it can be used, for
example, to produce drugs for the treatment of cardio-circulatory diseases, anti-inflammatory, anti
rheumatic, substitutive hormonal therapy and as pain therapy.
Essential oils Patches: the technology adopted for essential oils patches allows patients to inhale
decongestants or natural fragrances without using ointments or sprays. The active principle
evaporates gradually and is inhaled easily by the application of the patch on clothes at the chest
level. It doesn’t stain, doesn’t dirty and has a day-long action.
Oral fast delivery: this kind of technology enables to produce highly bioavailability microfilms,
and allows to immediate release a definite quantity of active principle orally. Oral fast delivery has
a wide range of applications among drugs and medical devices.
Diagnostics
Since 1975, Bouty has developed and manufactured diagnostic products for home and professional
use. Currently, the company is the major player in the domestic diagnostics market for autoimmuno
disease test reagents. In addition, Bouty is considered to be among the leading companies in the
following IVD market sectors:
� ToRCH (Toxoplasma, Rubella, Cytomegalovirus, Herpes panel)
� Syphilis and other STD
� Rheumatology
� Endocrinology
� Bone metabolism markers
� Pancreatic hormones
For some time now, Bouty has pioneered new diagnostic technologies. An example of which was
the Bouty 1994 acquisition of Technogenetics, that brought know-how suitable for:
� development and production of special monoclonal antibodies
� implementation of DNA recombinant techniques
� molecular investigations.
Paolo Barbanti The Italian pharmaceutical industry: trends and business opportunities © 30
The scientific challenges of the forthcoming era see the company involved in the development of
new products, PCR is based, in the following areas:
� Virology
� Genetics
� Oncovirology
� Immunology
The listed products are the state of the art ones in the infectious disease
testing,
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Paolo Barbanti The Italian pharmaceutical industry: trends and business opportunities © 32
Paolo Barbanti The Italian pharmaceutical industry: trends and business opportunities © 33
Paolo Barbanti The Italian pharmaceutical industry: trends and business opportunities © 34
Paolo Barbanti The Italian pharmaceutical industry: trends and business opportunities © 35
ALFA WASSERMANN
Paolo Barbanti The Italian pharmaceutical industry: trends and business opportunities © 36
CHIESI FARMACEUTICI
The company, founded in Parma in 1935, is today a dynamic reality in the pharmaceutical market
with global operations consisting of:
� 21 direct affiliates
� 3 manufacturing sites
� 3 research centres.
The Chiesi Group use over 2,700 employees, of whom 300 are involved in research and
development activities.
Chiesi Group has marketing and sales organisations in the majority of European countries: Italy,
France, Spain, UK, Germany, Greece, Austria, Poland, Hungary, Czech Republic, Slovenia,
Slovakia, Romania, Bulgaria and Russia. Italy is the largest market in terms of sales, followed by
France, Spain, UK, and Germany.
In addition to Europe, Chiesi is directly present in Brazil, Pakistan, Morocco, Algeria, Tunisia and
Egypt. In the USA, a small subsidiary is involved in clinical research and regulatory submissions.
Chiesi’s technologies and products are available in over 50 countries through a strategic alliances
network of international pharmaceutical groups developed both on a global and local scale.
Group turnover reached 565 million Euros in 2005.
Paolo Barbanti The Italian pharmaceutical industry: trends and business opportunities © 37
Chiesi's formula for success is based on a peculiar approach that allows to combine factors often
thought of as opposites in the pharmaceutical industry – such as research and ethics, technology and
humanity, commitment to results and concern for individuals, reliability and empathy – while
encouraging innovation at all levels.
Paolo Barbanti The Italian pharmaceutical industry: trends and business opportunities © 38
Research is the key to innovation, and according to a recent survey of the European Commission,
Chiesi Farmaceutici is one of the Italian groups with the highest investments in R&D. With
approximately 13-14% of the total turnover invested annually in R&D, Chiesi Farmaceutici is in
line with the largest European pharmaceutical groups.
Through these investments, Chiesi has generated more than 600 patents worldwide and 70% of
sales have come from internal research and development efforts. The Company has currently
collaborations with international research groups and academic centres producing synergies that can
help ensure Chiesi’s future research success.
Chiesi has 3 manufacturing facilities, located in:
� Parma (Italy)
� Blois-La Chaussée Saint Victor (France)
� Santana de Parnaiba (Brazil)
employing approximately 500 individuals.
Paolo Barbanti The Italian pharmaceutical industry: trends and business opportunities © 39
The manufacturing plant in Parma is an international supply site providing products to over 50
countries. It has been inspected successfully by several Health Authorities, including the USA FDA.
Chiesi Farmaceutici S.p.A. has been ISO 9001:2000 certified for “Research, Development,
Production and Sale of Medicinal Products”.
Specialised departments produce respiratory dosage forms, such as Metered-Dose Inhalers (MDI)
and sterile Unit Dose Vials (UDV) for nebulisation, using the best available “state-of-the-art”
technology, e.g. isolators and Blow Fill Seal aseptic techniques. The production and ancillary
processes (Cleaning in Place, Sterilizing in Place) are driven and monitored through validated
computer systems.
The capacity of new sterile UDV production department is being increased to over 200 million
doses per year. For MDIs, the current capacity is 13 million cans per year, using the HFA
Modulite® technology.
While in the past decade, the Group has grown due to the establishment of new companies in key
European countries, the contribution from Chiesi’s research and development to its“organic
growth” has been highly significant.
The number of “corporate” products is increasing mainly as a result of a number of successful
Mutual Recognition Procedures (MRPs) in Europe and through the obtainement of market
authorizations in several other countries worldwide.
Three units:
� Parma in Italy
� Paris in France
� Rockville in Maryland (USA)
employ over 300 people who work together on very focused drug discovery and development
endeavours in conjunction with major international medical centres.
In 2005, Chiesi invested 71 million Euros in R&D (12.6% of the Group revenues) plus 5 million
Euros in R&D capital expenditures.
Paolo Barbanti The Italian pharmaceutical industry: trends and business opportunities © 40
The goal of Chiesi is to become a recognised global player in pulmonology and to strengthen the
leadership position in neonatology, both areas in which we have strong competencies and an
established reputation.
To achieve these strategic objectives, the company has focused R&D activities on these two key
therapeutic areas, to maximise the value of internal resources and to reach a critical mass of
approximately 550 million Euros in R&D expenditures from 2006 to 2010.
Based on Chiesi’s proprietary Modulite®, a unique and environmentally-friendly HFA solution
technology for use in metered-dose inhalers - formoterol (Atimos®, Forair®) - was registered and
launched in Europe, and partnered with Novartis.
A fixed combination of formoterol and beclometasone was filed in Germany as Reference Member
State for a following MRP. The anticipated successful launch of this new product (Foster®)may
drive and accelerate the current promising development of carmoterol, a novel potential once-daily
beta-2 bronchodilator as well as its combinations with a steroid and a novel M3 antagonist for the
treatment of asthma and Chronic Obstructive Pulmonary Disease (COPD). Chiesi also developed,
together with Cambridge Consultants Ltd., a proprietary new-generation dry powder inhaler,
NEXTTM DPI.
This easy-to-use device may be suitable for all types of inhalation products and it may be used with
a DPI formulation of Foster®. The limited, but well focused and organised discovery program in
the respiratory field, has successfully identified interesting new chemical entities for further
development in clinically validated and new molecular targets as potential candidates in COPD, in
collaboration with Italian academic centres. In an effort to focus R&D pipeline, two innovative
CNS projects were out-licensed to Vernalis.
Paolo Barbanti The Italian pharmaceutical industry: trends and business opportunities © 41
DOMPE’
Dompé is one of the most dynamic, flexible and innovative set-ups on the European scene. A
successful in the traditional pharmaceutical market in the treatment of respiratory and osteoarticular
pathologies, Dompé has also developed its presence in the area of biotechnology with innovative
drugs and services
DRUGS
Dompé SpA
Primary care
• Arial (salmeterolo xinafoato)
• Artrosilene (ketoprofene sale di lisina)
• Fluifort (carbocisteina sale di lisina monoidrato)
• Frivent (teofillina anidra)
• Levotuss (levodropropizina)
• Miotens (tiocolchicoside)
• OKi (ketoprofene sale di lisina)
• Procef (cefprozil monoidrato)
• Prontinal (beclometasone dipropionato)
• Rexalgan (tenoxicam)
• decapinol (delmopinol) - Dispositivo Medico
• Ostenil (sodio ialuronato) - Dispositivo Medico
Aree Specialistiche
• Tobi (tobramicina)
• Provigil (modafinil)
• Actiq (fentanil citrato)
• Remodulin (treprostinil sodio)
Dompé Biotec SpA
Paolo Barbanti The Italian pharmaceutical industry: trends and business opportunities © 42
• Avonex (interferone β1a)
• Nespo (darbepoetina α)
• Neupogen (G-CSF)
• Neupopeg (pegfilgrastim)
• Parareg (cinacalcet)
• Gliadel (carmustina)
Biogen Dompé
• Avonex (interferone β1a)
• Tysabri (natalizumab)
Biogen Dompé AG (Svizzera)
• Avonex (interferone β1a)
Paolo Barbanti The Italian pharmaceutical industry: trends and business opportunities © 43
RESULTS
Annual sales summary
Draft subject to change. These values do not include intercompany sales
Research & Development
The research & development departments are integrated within Dompé. The core activities include
early discovery, preclinical and clinical development, registration and support to marketing.
R&D is mainly focusing on two major therapeutical fields:
� Immunology/Transplantation
� Oncology.
Paolo Barbanti The Italian pharmaceutical industry: trends and business opportunities © 44
Immunological Diseases/Transplantation
The major focus of Dompé research is to identify potent and specific inhibitors of pro-inflammatory
chemokines. Chemokines are a large family of small, structurally related proteins that mediate a
wide range of biological activities. Chemokines are essential mediators of normal leukocyte
trafficking but their role is not restricted to cell recruitment but to intervene in a variety of
pathophysiological processes including acute and chronic inflammation, angiogenesis, fibrosis,
infectious diseases and immunological disorders such as rheumatoid arthritis, atherosclerosis,
psoriasis and ulcerative colitis. Chemokines are multipotent cytokines that localize and enhance
inflamation by inducing chemotaxis and cell activation of different types of inflammatory cells
typically present at inflammatory sites. Chemokines and other mediators are secreted also by these
cells. Chemokines exert their functions through the selective binding to one or more seven-
transmembrane spanning, G protein-coupled receptors through which various signals are
transduced. Interleukin 8 (IL-8) is a chemokine that induces chemotaxis of neutrophils and is a
potent angiogenic agent. IL-8 is produced by stimulated monocytes, macrophages, fibroblasts,
endothelial cells, keratinocytes, melanocytes, hepatocytes, chondrocytes and a number of tumor cell
lines. In humans, there are at least two different IL-8 receptor types (type-1 and type-2). The
receptor is a dimeric glycoprotein consisting of 59 kDa and 67 kDa subunit and is expressed in
many different cell types including those which don't respond to IL-8. The receptor density is
approximately 20,000/cell in neutrophils and 300/cell in T-lymphocytes. IL-8 was reported to play a
pathophysiological role in post-ischemia reperfusion injury occurring after kidney, liver, heart or
lung transplantation or after myocardial ischemia or brain stroke. Reperfusion of ischemic tissues
induces the local production of IL-8 which recruits and activates neutrophils that in turn release a
number of tissue-damaging mediators. The discovery by Dompé laboratories of potent inhibitors of
the IL-8 activity has led to a potential innovative therapeutic approach for the treatment of
reperfusional damage and other conditions in which IL-8 is involved. Chemical entities acting as
dual inhibitors of IL-8 and C5a (a fraction of the complement cascade involved in the mechanism of
inflammatory cells recruitment) have been also characterized and contributed to the creation of a
molecular platform for inflammatory and immunological-related disorders. These chemical entities
would broaden the inhibition of inflammation in several pathological conditions which include post-
ischemic reperfusion injury and immunological-related disorders such as psoriasis, ulcerative
colitis, rheumatoid arthritis.
Paolo Barbanti The Italian pharmaceutical industry: trends and business opportunities © 45
Oncology
The main focus of Dompé is to discover and characterize human recombinant antibodies as
therapeutics mainly for treating neoplastic diseases but is also foreseen the cure of immunological
disorders. This biotechnology platform represents a state of art technology for the characterization,
purification and production of human recombinant antibodies which are gaining more and more
importance in the treatment of neoplastic and immunological diseases as well as in the diagnostic
field. The cloning and expression of human antibodies in E. coli presents numerous advantages over
the cloning and expression in mammalian cells, e.g. no risk for biological contaminants and
production costs are lower. Ovarian cancer has been identified as the principal therapeutic target of
our antibody platform technology. Ovarian cancer cells highly express the α-folate receptor (10-
100 folds the normal cells), thus this receptor represents an ideal therapeutic target. For therapeutic
purposes, in collaboration with the National Institute of Tumors of Milan, a fragment of a human
antibody (Fab) targeting the α-folate receptor (α-FR) present on the surface of most of the ovarian
cancer cells was identified, cloned and expressed in E. coli. The anti α-FR Fab is radiolabelled with
Yttrium and directed against the tumor. A murine monoclonal antibody (MOv 18) directed against
the same epitope and radiolabelled with Iodine has been successfully used in experimental models
in nude mice as well as in patients. In patients, bone marrow toxicity and host immunoreactivity
were the major concerns and represented limiting factors for radioimmunotherapy. A human
antibody Fab fragment would not only markedly reduce the immunogenicity but would also
facilitate the penetration of the radioconiugated antibody in the tumor. The shorter half life of
Yttrium and its deep penetration in tissues represents another additional advantage to the traditional
radiotherapy
COMPETENCES
Research profile
Pharmacology
• In vitro and in vivo models of inflammation, transplantation, respiratory and
cancer diseases.
• Preclinical pharmacokinetics studies in rodents.
Biotechnology
Paolo Barbanti The Italian pharmaceutical industry: trends and business opportunities © 46
• DNA cloning, phage display, identification and purification of fragments of
human antibodies to be used as therapeutic tool.
Pharmaceutical Development
• Structural, chemical and physical analysis.
• Preformulation and formulation studies (oral, injectable and topical formulations)
stability, scale-up.
Chemistry
• Molecular design, organic synthesis, peptide synthesis.
Paolo Barbanti The Italian pharmaceutical industry: trends and business opportunities © 47
R & D PROJECTS
Development Pipeline
Pharmaceutical manufacturing
The pharmaceutical plant, designed and constructed by the Foster-Wheeler engineering company,
was inaugurated in 1993 and constitutes the very latest evolution in company production know-
how, which took root at the beginning of the last century. The production facilities are validated
internationally and have a production potential of many tens of millions of units per year of topical
products, oral fluids and solids, combining the highest levels of quality with competitive costs. The
level of supervision of the production activities and the environmental parameters is augmented by
validated computerized systems which conform to the latest GMP standards in current use. The
control of the environmental characteristics of the premises where the storage, dosed distribution
and production activities take place, is carried out on a continuous basis by a DCS System which
Paolo Barbanti The Italian pharmaceutical industry: trends and business opportunities © 48
makes it possible to gain real time knowledge of differential levels in the pressure, humidity and
temperature to which the processes are subjected. A natural consequence of Dompé’s quest for total
quality has been the certification, obtained in the last two years, relative to the management of the
Quality System ISO 9001 and the Environmental Management System ISO 14001.
Dompé SpA
This Company draws up and provides services of updating and scientific assistance to doctors of
General Medicine, Paediatrics, Pneumology, Otology, Orthopaedics, Rheumatology, Physiatrics,
Odontology, Accident & Emergency and First Aid stations. It guarantees information to the
Pharmacist, both within the hospital and outside, contributing to the development of the citizen's
education in terms of health.
It offers innovative solutions and efficient services to work alongside the National Health Service in
the treatment of respiratory pathologies and osteoarticular disease for the sake of improving the
patient’s quality of life.
THERAPEUTIC AREAS
• Physiatrics
• Cystic Fibrosis
• Sleep Medicine
• Geriatrics
• Infectious diseases
• Internal Medicine
• Sports Medicine
• Odontology
• Orthopaedics and Traumatology
• Otorhinolaryngology
• Paediatrics
• Pneumology
• Emergency
DRUGS
Paolo Barbanti The Italian pharmaceutical industry: trends and business opportunities © 49
Primary Care
• Arial
• Artrosilene
• Fluifort
• Frivent
• Levotuss
• Miotens
• OKi
• Procef
• Prontinal
• Rexalgan
• decapinol (device)
• Ostenil (device)
Specialist Care
• Tobi
• Provigil
• Actiq
• Remodulin
Dompé farmaceutici SpA
Almost a century after its foundation, Dompé Farmaceutici SpA has now moved into the field of
rare pathologies, with the aim of providing the medical class and the patient with pharmaceutical
products of high therapeutic value, often distinguished by their high technological content. Dompé
farmaceutici declares its express undertaking with regard to Cystic Fibrosis through the distribution
of drugs with a high technological content, through its collaboration with specialist centres and in
the creation of educational projects dedicated to the doctor and the patient.
THERAPEUTIC AREAS
• Palliative Care
Paolo Barbanti The Italian pharmaceutical industry: trends and business opportunities © 50
Dompé Biotec SpA
Dompé Biotec is exclusively concerned with biotechnological pharmaceuticals of high therapeutic
value. It is the leading company in Italy both in terms of number of biotechnological drugs on the
market and the number of patiets treated.All these drugs are used in specialist fields, mainly in the
hospital setting.
THERAPEUTIC AREAS
• Haematology
• Infectious diseases
• Nephrology
• Oncology
• Transfusion units
• Neuro-Oncology
DRUGS
• Nespo
• Neupogen
• Neupopeg
• Parareg
• Gliadel
Dompé pha.r.ma SpA
Dompé pha.r.ma researches and develops innovative drugs for serious and debilitating pathologies;
it produces medical specialities of its Group and of selected Partners. The goal of R&D is to
improve the quality of life of patients suffering of life-threatening or debilitating diseases. To this
aim, R&D is committed to the discovery and clinical development of innovative drugs.
Dompé International SA
Dompé International was founded in 1997 with the aim of internationalizing Dompé activities by
either boosting international and export sales and by increasing licensing contacts as well as
developing technology exchange with other companies. Dompé International monitors fast
Paolo Barbanti The Italian pharmaceutical industry: trends and business opportunities © 51
developing markets in order to identify business opportunities in the core business therapeutic areas
of the company.
PARTNERSHIPS
Dompé S.p.A.
• Aziende Chimiche Riunite Angelini Francesco ACRAF S.p.A. - Levotuss
• F.I.R.M.A. S.p.A. - Levotuss
• Sigma-Tau Industrie Farmaceutiche Riunite S.p.A. - Levotuss
• Stada / Ciclum Farma S.A. - Levotuss, Fluifort
• Boehringer Ingelheim Ellas A.E. - Levotuss
• Boehringer Ingelheim Italia S.p.A. - Artrosilene
• Italfarmaco S.A. - Fluifort
• GlaxoSmithkline - Arial
• Bristol-Myers Squibb S.p.A. - Procef
• Roche S.p.A. - Rexalgan
• Schering-Plough Products Inc. - Frivent
• TRB Chemedica S.A. - Ostenil
• Chiron Corporation - Tobi
• Cephalon (UK) Limited - Actiq, Provigil
• United Therapeutics Europe Ltd - Remodulin
Dompé pha.r.ma S.p.A.
Ricerca e Sviluppo
• Biofocus plc
• Bio-Quant Inc.
• Consorzio Interuniversitario Nazionale "Metodologie e Processi Innovativi di Sintesi"
(C.I.N.M.P.I.S.)
• Consorzio per la Costituzione di Milano Ricerche
• Istituto Nazionale per lo Studio e la Cura dei Tumori
• Istituto di Ricerche Farmacologiche "Mario Negri" - Laboratori Negri Bergamo
• Istituto di Ricerche Farmacologiche "Mario Negri" - Milano
Paolo Barbanti The Italian pharmaceutical industry: trends and business opportunities © 52
• Consorzio Mario Negri Sud
• Università degli Studi di Milano
• Università degli Studi di Torino
• Rega Institute - University of Leuven
• Xoma Ireland Limited
Produzione
• Boehringer Ingelheim Italia S.p.A.
• A. Menarini Manufacturing Logistics and Services S.r.l.
• Roche S.p.A.
Dompé Biotec S.p.A.
• Amgen (Europe) A.G. / Amgen Inc. - Nespo, Neupopeg, Neupogen, Parareg
• Guilford Pharmaceuticals Limited - Gliadel
Biogen Dompé
• Biogen B.V. - Avonex, Tysabri
Biogen Dompé AG (Switzerland)
• Biogen B.V. - Avonex
Paolo Barbanti The Italian pharmaceutical industry: trends and business opportunities © 53
MENARINI
Menarini was established over a century ago (as many Italian pharmaceutical companies) in a small
laboratory of the Farmacia Internazionale of Naples. In 1915, it transferred to Florence, where it its
head office is still located. Since 1978 Menarini has established a series of agreements with some
important Italian companies: the first agreement was with Malesci which was followed by
agreements signed with Guidotti, Lusofarmaco, Lusochimica and Firma.
The aim of these agreements has been a better organization of the strategic areas of Research and
Development and of Internationalization, as well as reaching maximum efficiency in the chain of
production and supply.
In 1976, activity in the Diagnostics Division was added to the existing ethical drug production and
in 1994 the OTC Division was started.
Today the Menarini Group is the first Italian pharmaceutical group in the world and is present:
� in all countries of the European Union (except the Scandinavian countries)
� in Switzerland
� in Central and Eastern European countries
� in Central America where it ranks at the fifth position
� in the main developing countries such as India, Vietnam, People's Republic of China and
Korea
� in South Africa
� in Argentina (opening of the affiliate from April 2001)
The Group is also present with its own products in over 100 countries in the world using agents and
local distributors.
EUROPE: in addition to Italy where Menarini is the leading pharmaceutical group, sales are
mainly concentrated in Europe: Austria, Benelux, France, Germany, United Kingdom,
Greece, Ireland, Portugal, Spain, Turkey and Switzerland.
Paolo Barbanti The Italian pharmaceutical industry: trends and business opportunities © 54
CENTRAL AMERICA / LATIN AMERICA: Menarini is present in all Central American
countries and there it is ranked among the top five pharmaceutical companies. Menarini also
has representative agents in Mexico, Colombia, Venezuela, Chile, Ecuador and Peru. The
affiliate in Argentina has been opened in April 2001.
ASIA: Menarini has created a Joint Venture in India and has a representative office in
China. Currently, it is consolidating its presence in the People's Republic of China, in
Vietnam and in South Korea. In other countries, Menarini is represented by agents and
distributors mainly in Bangladesh, Indonesia, Hong Kong, Malaysia, Taiwan and Thailand.
AFRICA and the MIDDLE EAST : In Africa and the Middle East, Menarini's products are
managed by agents and distributors whose promotional activities are controlled by the
Company.
RESULTS
2003
1,802 mill. Euros
51% of this abroad
2004
1,869 mill. Euros
55% of this abroad
2005
2,234 mill. Euros
The Research Activity of the Menarini Group centres on a single pole, Menarini Research, which
deals with all R&D activities from the initial stage of new projects to the registration stage.
Paolo Barbanti The Italian pharmaceutical industry: trends and business opportunities © 55
The research programmes are divided up among the following centres:
• Florence
• Pomezia (Rome)
• Milan
• Pisa
• Barcelona
• Berlin
and essentially address the following research areas:
� Cardiovascular diseases
� Oncology
� The pain/inflammation/asthma area
Product’s portfolio
The Menarini Group has a hold in the most important therapeutic fields. They are:
� cardiovascular
� gastro-intestinal
� antibiotics respiratory
� anti-diabetics
� anti-inflammatory/analgesics
and many others.
Paolo Barbanti The Italian pharmaceutical industry: trends and business opportunities © 56
Menarini Diagnostics
The Company was founded in 1976 as a division of A. Menarini Industrie Farmaceutiche Riunite of
Florence, Italy. The average annual growth of the Company turnover for the last four years is
around 16%. In July 1997 A. Menarini Diagnostics was certified by the TÜV Product Service
according to the ISO 9002 and EN 46002. In July 2003, the Company obtained by TÜV the
certification ISO 9001:2000, ISO 13485:2000.. Now, A. Menarini Diagnostics employs
approximately 700 people, 75% of whom are dedicated to marketing, sales, after-sales service and
customer care activities. The 2005 consolidated turnover reached approximately 256 million Euros.
Today, A. Menarini Diagnostics is an International Group and its headquarters are located in
Florence. Additionally, there is an infrastructure made up of ten fully owned subsidiaries in:
� Austria
� Belgium
� France
� Germany
� Greece
� The Netherlands
� Portugal
� Spain
� United Kingdom
� Sweden.
The strategic fields of A. Menarini Diagnostics are:
� Diabetes (self testing & laboratory systems)
� Clinical Chemistry (dry, wet and urinalysis)
� Haematology (blood typing, ESR, cell counting).
� Immunology (immunohistochemistry, autoimmunity, immunometric assays).
Menarini Diagnostics has established a number of successful partnerships with leading producers
including Arkray KDK Corporation (Japan), Inova (USA), Diesse (Italy), CLB (The Netherlands).
Paolo Barbanti The Italian pharmaceutical industry: trends and business opportunities © 57
Main products and product lines are:
� Glucocard glucose self-testing potentiometric system
� GlucoMen glucose self-testing potentiometric system
� GlucoDay® S continuous glucose monitoring system
� Menagent Easy ready-to-use multipurpose liquid reagents for clinical
chemistry
� Spotchem easy-to-use dry chemistry analyser for Doctor Office and the
veterinary diagnostics.
� Aution Orchestra fully automated urinalysis system
� Vesmatic System automatic system for ESR (Erytro Sedimentation Rate)
measurement
� Ha 8160 fully automated haemoglobin analyser
� Inova a complete program of reagents for autoimmunity.
Paolo Barbanti The Italian pharmaceutical industry: trends and business opportunities © 58
RECORDATI
Recordati, established in 1926, is a European pharmaceutical group, listed on the Italian Stock
Exchange (Reuters RECI.MI, Bloomberg REC IM, ISIN IT 0003828271), dedicated to the research,
development, manufacturing and marketing of pharmaceuticals, with headquarters in Milan, Italy. It
operates in the main countries Of Europe with a total staff of over 2,000.
A European field force of over 1,000 medical representatives promotes a wide range of innovative
pharmaceuticals, both proprietary and licensed, in a number of therapeutic fields. Recordati’s
current and growing coverage of the European pharmaceutical market makes it a partner of choice
for new product licenses of companies that do not have European marketing organizations.
Recordati is committed to the research of new drug entities within the cardiovascular and urogenital
therapeutic fielss in which its research team has proven scientific competence and a track record of
discovery and development of original drugs. The most recent product is lercanidipine, a latest
generation calcium channel blocker for the treatment of hypertension considered to be the
company’s leading product.
Recordati operates directly in France, Germany, Greece, Ireland, Italy, Portugal, Spain and United
Kingdom. In these countries, it does not only market original pharmaceutical specialties, but it also
promotes innovative in-licensed pharmaceuticals.
Thanks to numerous licensing agreements with international pharmaceutical companies, Recordati's
innovative proprietary pharmaceuticals (lercanidipine, flavoxate, fenticonazole) are distributed in
approximately 100 countries.
Consolidated revenue for 2006 was 576.2 million Euros, operating income was 120.3 million Euros
and the net income was 74.0 million Euros.
Paolo Barbanti The Italian pharmaceutical industry: trends and business opportunities © 59
Economic & Financial Data
Key Data
(m €)
2002 2003 2004 2005 2006
Net Sales 492.7
(100%)
487.5
(100%)
488.3
(100%)
576.1
(100%)
576.2
(100%)
Operating Income 89.2
(18.1%)
81.0
(16.6%)
90.4
(18,5%)
111.1
(19.3%)
120.3
(20.9%)
Net Income 50.2
(10.2%)
23.7
(4.9%)
54.0
(11.1%)
64.5
(11.2%)
74.0
(12.8%)
Net Sales
Sales by Business
Paolo Barbanti The Italian pharmaceutical industry: trends and business opportunities © 60
Pharmaceuticals: Net Sales
Paolo Barbanti The Italian pharmaceutical industry: trends and business opportunities © 61
Key P&L and Cash Flow
(m €)
2002 2003 2004 2005 2006
Net Sales 492.7 487.5 488.3 576.1 576.2
Gross profit
as % of Sales
289.1
58.7%
287.8
59.0%
309.0
63.3%
375.5
65.2%
384.2
66.7%
Operating Income
(EBIT) as % of Sales
89.2
18.1%
81.0
16.6%
90.4
18.5%
111.1
19.3%
120.3
20.9%
Pretax Income 80.7 38.4 86.7 107.0 118.2
Net Income 50.2 23.7 54.0 64.5 74.0
CASH FLOW 84.2 80.5 76.9 89.0 97.3
Per Share Data
2002 2003 2004 2005 2006
Earnings per share (EPS) 0.2525 0.1225 0.270 0.326 0.370
Cash flow per share 0.4225 0.4125 0.387 0.45 0.487
Paolo Barbanti The Italian pharmaceutical industry: trends and business opportunities © 62
Balance Sheet Structure
Paolo Barbanti The Italian pharmaceutical industry: trends and business opportunities © 63
Corporate Structure
Paolo Barbanti The Italian pharmaceutical industry: trends and business opportunities © 64
RESEARCH AND DEVELOPMENT
Drugs are sourced either internally through original research activities or externally through
partnerships with other pharmaceutical companies.
Recordati conducts development activities in the field of cardiovascular diseases; the related
hypertension Recordati’s efforts in this area, led to the discovery of lercanidipine, a latest
generation drug belonging to the widely used calcium channel blocker class.
Zanitek®, a fixed combination of lercanidipine and enalapril and by Recordati, is a new specialty
indicated for the treatment of hypertension developed.
Recordati’s original research is primarily focused on the search for treatments for micturition
disorders. In this field, the researchers at Recordati are working on projects for innovative drugs
that act through new mechanisms of action or on various combinations.
Pipeline
NAME ORIGINATOR INDICATION PHASE
Project S Recordati Chronic Heart Failure
(CHF)
Discovery
2 new projects Recordati Overactive bladder and
Incontinence
Discovery
REC 0035 Recordati Benign prostatic
hyperplasia
Preclinical
REC 2615 Recordati Sexual dysfunction,
female
Reformulation
new
lercanidipine
Recordati Hypertension Formulation
Paolo Barbanti The Italian pharmaceutical industry: trends and business opportunities © 65
combinations
lercanidipine
MR
Different technology
platforms
Hypertension, general Formulation /
Phase II
pitavastatin Kowa Hyperlipidemia, general Phase III
Stanate® Rockefeller U. / InfaCare Neonatal jaundice,
hyperbilirubinemia
Phase II / III
silodosin Kissei Benign prostatic
hyperplasia
Phase III
prulifloxacin Nippon Shinyaku /
Angelini
Infection, respiratory
tract, urinary tract
Phase III
Infasurf® Ony Calf derived surfactant Pre-filing
fentanyl patch Lavipharm Moderate to severe
chronic pain
Filed in the RMS
(UK)
rupatadine Uriach Rhinitis, allergic,
seasonal / perennial
urticaria
Approved
Zanipress® /
Zanitek®
Recordati Hypertension
(lercanidipine +
enalapril)
Launched in the
RMS (Germany)
RMS - Reference Member State
Manufacturing Facilities
Milan (Italy)
The Group's principal pharmaceutical manufacturing site is in Milan. The premises measure 25,000
square metres, and the plant has a production capacity of 45 million units per year. It specializes in
the manufacturing and packaging of oral solid, drops, injectables and topical formulations. Situated
Paolo Barbanti The Italian pharmaceutical industry: trends and business opportunities © 66
in Milan and licensed to produce pharmaceutical specialties for the major international markets, the
plant is designed to ensure the highest manufacturing standards in compliance with CGMP (Current
Good Manufacturing Practices) standards; it operates in conformity with the most stringent
international environmental regulations.
Campoverde di Aprilia (Latina, Italy)
The high-tech facility covering an area of over 360,000 square metres, has an installed capacity of
800 cubic metres. In this site, by employing chemical syntheses, active ingredients are produced for
Recordati pharmaceutical brands, and large-scale active ingredients and active ingredients are
manufactured for international markets.
The plant operates in accordance with the cGMP (current Good Manufacturing Practices) and in
conformity with the most stringent international environmental regulations. It is regularly inspected
by the FDA, by other national and international authorities as well as our customers.
The Plant Environmental Management System, has gotten the certification in 2003, according to the
UNI EN ISO 14001: 1996 norm, subsequently confirmed according to UNI EN ISO 14001: 2004
norm. The certification was been released by the International Accredited Unit DNV (Det Norske
Veritas, Italy).
Montluçon (France)
Montlucon in France is the pharmaceutical manufacturing facility of Bouchara Recordati. Covering
an area of approximately 3,500 square metres, the plant is licensed to produce and package oral
liquid, solid formulations and sprays. It has a manufacturing capacity of 20 million units per year.
The plant is designed to ensure the highest manufacturing standards in compliance with GMP
(Good Manufacturing Practices) standards; it operates in conformity with the most stringent
international environmental regulations.
Ringaskiddy, Cork (Ireland)
The site, which covers the area of 4.21 hectares, is located in the pharmaceutical industrial area of
Ringaskiddy, approximately 15km from Cork, the second largest city in Ireland. The lercanidipine
Paolo Barbanti The Italian pharmaceutical industry: trends and business opportunities © 67
manufacturing facility became operational at the end of 2005. A GMP (Good Manufacturing
Practices) certificate was issued by The Irish Medicines Board in December 2005.
Raw materials
The pharmaceutical chemicals business accounts for 6% of Recordati’s total revenue. Recordati
produces both active ingredients for its own proprietary pharmaceuticals, and active ingredients and
intermediates for the generic drugs market.
Recordati exports around 90% of its production of API’s and intermediates by selling its products
directly to over 50 countries.
Paolo Barbanti The Italian pharmaceutical industry: trends and business opportunities © 68
SIGMA – TAU
Sigma Tau is one of the most important Italian pharmaceutical groups, it employs 2,366 people and
its corporate turnover in 2005 amounted to € 674 million.
The drive towards internationalization is best testified by the constant development of new
cooperation agreements with many scientific institutes in Europe and North America.
Paolo Barbanti The Italian pharmaceutical industry: trends and business opportunities © 69
Sigma - Tau is a company whose main objective is to help improve health and the quality of life for
everybody.
To achieve these goals, the company operates in all the clinically important therapeutic sectors and
the huge investments devoted to research - 16% of corporate turnover - are at the basis of its
business
Sigma-Tau employs over 400 researchers, providing them with the means and resources to develop
therapeutic breakthroughs that can better guarantee health conditions for everyone. All this requires
considerable investments.
The Company has opened branches in France, Switzerland, the Netherlands, Portugal, Germany and
other countries in Europe
Paolo Barbanti The Italian pharmaceutical industry: trends and business opportunities © 70
R & D PROJECTS
ACTIVITIES AND PROJECTS -
Cardiovascular disease, metabolism, oncology, immunology, central and peripheral nervous system.
50 projects, 33 clinical indications studied with 18 molecules of property of Sigma Tau, and most of
which (15) are new and original.
This is the scope and the dimension of internal research, which is carried out in the following
facilities:
� Sigma-Tau Research Centre (Pomezia, RM)
� Prassis Research Institute (Settimo Milanese, MI)
� Tecnogen S.p.A. (Piana di Monte Verna, CE)
� Kenton srl (Pomezia, RM)
� Sigma-Tau Research Inc. (Gaithersburg, MD).
Paolo Barbanti The Italian pharmaceutical industry: trends and business opportunities © 71
R & D PROJECTS
Therapeutic
Area Drug Indication State of Progress
β4 Thymosin Rip. stasis related
venous wounds and
ulcers
Stage 2 study in
programme*
Istaroxime Heart failure Stage 2**
Rostafuroxin Hypertension Stage 2
Cardiovascular
disease
Propionyl-L-carnitine Intermittent
Claudication
Pre-registration (U.S.A.)
L-carnitine Transplant medicine Stage 2 study in
programme
L-carnitine Peritoneal dialysis Stage 2
Teglicar Type 2 diabetes Stage 2
Metabolism
Propionyl-L-carnitine Dialysis Stage 2; Stage 3 study in
programme
ST 1968 Misc. tumours Preclinical development
Vaccine Misc. tumours Start of clinical trials in
programme
ST 1926 Misc. tumours Stage 1
Gimatecan Misc. tumours (solid) Stage 2#
Acetyl-L-carnitine Chemotherapeutic
neuropathy
Stage 3
Oncology
Defibrotide Occlusive venous
disease
Stage 3 (USA)##
ST 1959 Autoimmune
diseases
Preclinical development
PTX 3 Immunotherapy Preclinical development
Radioimmunotherapy
antibody-guided (PAGRIT®)
Glioma and misc.
tumours
Stage 1
Immunology
Intraoperative avidination Misc. tumours Stage 1
Paolo Barbanti The Italian pharmaceutical industry: trends and business opportunities © 72
for radiotherapy (IART®)
Propionyl-L-carnitine Intestinal
inflammatory disease
Stage 2 study in
programme
∂1 Thymosin Melanoma, Liver
cancer
Stage 2/3^
∂1 Thymosin Hepatitis C, Hepatitis
B
Stage 3^
DHA/PPQ
(Dihydroartemisinin/Piperaquine)
Malaria Stage 3^^
Patch Ibuprofene Soft tissue
inflammation
Registration
ST 2472 Schizophrenia Preclinical development
ST 1535 Parkinson's Disease Preclinical development
Central
Nervous
System ST 1859 Alzheimer's Disease Preclinical development
ST 983 Liposomial
preparations
Preclinical development
Other
ST 1898 Acne Preclinical development
Cardiovascular disease - Sigma-Tau has discovered and patented Istaroxamine, an innovative
agent (drug) for the treatment of Heart Failure, which is currently in State 2 clinical studies and
object of a research development and in terms of marketing agreement with Debiopharm SA
(Switzerland). Moreover, currently clinical studies are ongoing for a new hypertension treatment
(Rostafuroxime).
Metabolism - Research on type 2 diabetes is currently focussed on developing drugs that can
control glucose levels without causing serious secondary metabolic changes.
Immunology and inflammation - Research on non-steroid anti-inflammatory drugs and molecules
that control the activity of inflammation mediators.
Paolo Barbanti The Italian pharmaceutical industry: trends and business opportunities © 73
Oncology and immunology - A multiple approach to tumour therapy, recognizing the importance
of research in tumour therapy, and, believing in the importance of trying different therapeutic
approaches, developing research programmes on new antitumour drugs that act by means of
different mechanisms (cytotoxic, antiangiogenetic, cytodifferentiated), on somatic cell therapy
(cancer vaccine) and on a radioimmunotherapy kit. This cutting-edge programme is unique in
placing different approaches and techniques side by side and has produced a wealth of important
data. Of special significance is the work on biotechnologies, and particularly the development of
PAGRIT® (Pretargeted Antibody-Guided RadioImmuno Therapy), based on original tumour-
specific monocloned antibodies which are selectively carried to the tumour. The project, which
originated at the European Institute of Oncology, is being carried out with the participation of
Tecnogen. Among the other projects, a special mention must be reserved for Gimatecan, an oral
antitumor drug belonging to the family of topoisomerase-1 inhibitors, which has been developed in
Italy (University of Milan, Istituto dei Tumori in Milan and Sigma Tau). Gimatecan has been
licensed for co-development by Novartis, a leading concern in oncology research, which has
acquired the worldwide selling rights for the product. The drug is currently in Stage 2.
Central and Peripheral Nervous System –
In neuropharmacology, research at Sigma-Tau follows three main lines:
- the study of molecules that show potential applicability against neurovegetative diseases,
such as Alzheimer's disease, multiple sclerosis or encephalomyielitis;
- the study of new atypical anti-psychotic drugs for the treatment of schizophrenia with
fewer side effects;
- the study of drugs for the treatment of Parkinson's disease which work by a new action
mechanism (A2a antagonists).
An area in which Sigma-Tau is especially proud of its results is the field of rare diseases, the
commitment to rare diseases is underlined by the fact that Sigma-Tau was the fourth company in the
world to obtain the United States Orphan Drug Designation, in 1984, after which it received seven
more; five new designations have been requested from European authorities.
Sigma Tau has recently established cooperation relationships with China which are fully in line
with the Company's approach to the study of natural molecules of particular interest for research. .
Together with the Chinese company Chongqing Holley, the Company has launched a project
directed at internationally registering an anti-malaria drug, in which Sigma-Tau makes its industrial
Paolo Barbanti The Italian pharmaceutical industry: trends and business opportunities © 74
know-how available in order to guarantee the distribution of the drug in those countries where
malaria still culls millions of victims. In addition, still with Chongqing Holley, as well as with other
Chinese partners, opportunities are being explored to investigate new compounds for the
development in important therapeutic areas, including oncology, making use of the millenary
experience of traditional Chinese medicine.
Another important field of research made by Sigma-Tau is the development of drugs designed for
the treatment of individual patients rather than the disease in general. Hence the study of vaccines
for specific forms of cancer in individual patients, or the development of antihypertensive drugs for
groups of hypertensive patients who share particular genetic features.
FACILITIES:
- Research Centre - Pomezia (RM) - The Research Centre is located at the centre of
Pomezia's industrial estate, marking the importance that Sigma-Tau assigns to the
relations between research and corporate activities. The Research Centre covers
24,000 square metres and hosts approximately 300 researchers. This is where all
drug synthesizing, discovery and preclinical development activities (Pharmacology,
Toxicology, Analytic, etc.) are carried out. The complex also houses the Medical
Supervision and Regulation Affairs offices, which are the divisions involved in
coordinating clinical activities and drug registration worldwide.
- Prassis Research Institute - Settimo Milanese (MI) - The Prassis Research
Institute was created by the Sigma-Tau Group at Settimo Milanese in 1989. The
Institute is divided into two scientific divisions (Chemistry & Analysis,
Cardiovascular Pharmacology) and an Administration Division. The complex was
restored during 1996-1999 to comply with the new legislation on environmental
safety. Research is carried out by a staff of 50 people and is performed in close
coordination with Sigma-Tau's corporate Research and Development structure, of
which the Prassis Institute represents the sector specialised in cardiovascular
diseases.
- Tecnogen - Piana di Monte Verna (CE) - Located in Piana di Monte Verna, in the
province of Caserta, Tecnogen carries out biotechnology research for pharmaceutical
applications, and has acquired specific experience in peptide combinatorial libraries
and pharmaceutical proteins. Tecnogen has recently been authorized to produce
monoclonal antibodies and recombinant proteins for use in clinical experiments.
Paolo Barbanti The Italian pharmaceutical industry: trends and business opportunities © 75
- Kenton srl - Pomezia (RM) - Kenton is specifically qualified in biotechnologies
applied to the development of methods for the early diagnosis of tumours and of
infections caused by the hepatitis C virus in humans.
- Sigma-Tau Research Inc. - Gaithersburg, MD - The Group's R&S activities are
completed by Sigma-Tau Research Inc., which follows the clinical development of
Sigma-Tau products in the United States. These facilities cover an area of 36,500
square metres. Research activities are often carried out together with the
collaboration of leading academic institutes, many of which are in Italy, such as the
Istituto dei Tumori in Milan, the European Institute of Oncology, and various
universities, including Rome, Milan, Parma, Siena, Brescia and Bari.
PRODUCTS
THERAPEUTIC AREAS
Sigma Tau products include a wide range of products in important
therapeutic areas:
� the cardiovascular and metabolic area includes drugs for the treatment of hypertension,
ischemic heart disease, rhythm disorders, hyperlipoproteinemia and thrombosis.
Cardiovascular drugs include: nitro derivatives, calcium antagonists, ACE-inhibitors,
angiotensin II antagonists, statins, an antiplatelet drug, omega-3 polyunsaturated fatty acids
and bemiparin, a second-generation low molecular weight heparin. In addition, a new drug
is being studied for the treatment of heart failure which is currently in Stage 2 of the clinical
trials; it is a completely new drug that combines lusitropic action with a strong inotropic
effect without increasing oxygen consumption. A new drug is in the development phase for
the treatment of hypertension (Rostafuroxin) which normalizes changes in the tubular
reabsorption of sodium associated with hypertension without interfering with other receptors
involved in regulating arterial pressure or hormonal homeostasis and without inducing the
effects typically caused by diuretics;
Paolo Barbanti The Italian pharmaceutical industry: trends and business opportunities © 76
SIGMA-TAU PHARMACEUTICALS FOR
CARDIOLOGY
ACESISTEM Enalapril + Hydrochlorothiazide
AMIODAR Amiodarone
DILZENE Diltiazem
ESKIM Polyunsaturated fatty acid ethyl
esters
ESRADIN Isradipine
IVOR Bemiparin
LIBRADIN Barnidipine
LOSAPREX Losartan
LOSAZID Losartan + Hydrochlorothiazide
NAPRILENE Enalapril
NEOPREX Enalapril + Hydrochlorothiazide
NITRO-DUR Nitroglycerine
SIVASTIN Simvastatin
TICLODONE Ticlopidine
the gastroenterology area includes antiulcer drugs, H2 receptor antagonists and proton pump
inhibitors, modulators of intestinal motility and probiotics;
SIGMA-TAU PHARMACEUTICALS FOR
GASTROENTEROLOGY
FAMODIL Famotidine
LIMPIDEX Lansoprazol
VSL#3 Milk enzymes
YOVIS Milk enzymes
Paolo Barbanti The Italian pharmaceutical industry: trends and business opportunities © 77
� the respiratory area presents innovative products, for the treatment of asthma and
obstructive syndromes of the respiratory tracts, such as an antileukotriene and the
association between beta-2 adrenergic receptor agonists and a corticosteroid;
SIGMA-TAU PHARMACEUTICALS FOR
PNEUMOLOGY
LUKASM Montelukast
SINESTIC Budesonide + Formoterol
� the infectious disease area includes oral and injectable antibiotics, either on their own or in
predetermined associations, that can inhibit the activity of a number of pathogens, and
antiviral drugs for systemic applications;
SIGMA-TAU PHARMACEUTICALS FOR INFECTIOUS
DISEASES
ACTIRA Moxifloxacin
AMPLIUM Ampicillin + Cloxacillin
LORICIN Ampicillin + Sulbactam
SPECTRUM Ceftazidime
TALAVIR Valacyclovir
TENACID Imipenem + Cilastatin
TROZOCINA Azithromycin
VIRUXAN Metisoprinol
� the urologic area offers a drug for the treatment of benign prostatic hypertrophy based on
finasteride, an inhibitor of the enzyme 5-alpha-reductase;
Paolo Barbanti The Italian pharmaceutical industry: trends and business opportunities © 78
SIGMA-TAU PHARMACEUTICALS FOR UROLOGY
PROSTIDE Finasteride
� the rheumatologic area is represented by etoricoxib, a second-generation COX-2 inhibitor,
a Tenoxicam based Fans, a transdermic preparation (patch) based on Ketoprofene and a
local Felbinac based gel base for symptomatic treatment of osteoarticular and muscle-tendon
pathologies;
SIGMA-TAU PHARMACEUTICALS FOR
RHEUMATOLOGY
DOLMEN Tenoxican
KEPLAT Ketoprofene
TAUXIB Etoricoxib
TRAXAM GEL Felbinac
� in the area of bone metabolism and osteoporosis, we have alendronate, of the
biphosphonates family, a molecule that finds application in the treatment of osteoporosis;
SIGMA-TAU PHARMACEUTICALS FOR
OSTEOPOROSIS
DRONAL Alendronate
� the neurological area, offers a combination for the symptomatic treatment of migraine, as
well as l-acetylcarnitine for use in peripheral neuropathies;
SIGMA-TAU PHARMACEUTICALS FOR
Paolo Barbanti The Italian pharmaceutical industry: trends and business opportunities © 79
NEUROLOGY
MIGRAPRIM Lysine acetylsalicylate +
Metoclopramide
ZIBREN Acetylcarnitine
� Sigma-Tau recognizes the importance of research in tumour therapy, and, believing in the
importance of trying different therapeutic approaches, has developed research programmes
on new antitumor drugs with different action mechanisms (cytotoxic, antiangiogenic,
cytodifferentiated), on somatic cell therapy (cancer vaccine) and on a radioimmunotherapy
kit.
SIGMA-TAU PHARMACEUTICALS FOR ONCOLOGY
GELCLAIR Polyvinylpirrolidone + Ialuronic acid
+ Glycyrrhetinic acid
NATULAN Procarbazine
TARGRETIN Bexarotene
This cutting-edge programme is unique in putting different approaches and techniques side by side
and has produced a wealth of important data. Of special significance is the work on
biotechnologies, and particularly the development of PAGRIT® (Pretargeted Antibody-Guided
RadioImmuno Therapy), based on original tumour-specific monoclonal antibodies which are
selectively carried to the tumour. The project, which originated at the European Institute of
Oncology, is being performed by the participation of Tecnogen. Among the other projects,
Gimatecan merits a special mention; this is an oral antitumor drug belonging to the family of
topoisomerase-1 inhibitors which has been developed in Italy (University of Milan, Istituto dei
Tumori in Milan). Gimatecan has been licensed for co-development by Novartis, a leading concern
in oncology research, which has acquired the worldwide selling rights for the product. The drug is
Paolo Barbanti The Italian pharmaceutical industry: trends and business opportunities © 80
currently in Stage 2.
LIST OF PRODUCTS BY BRAND NAMES
LIST OF PRODUCTS BY BRAND NAME
ACESISTEM Enalapril + Hydrochlorothiazide
ACTIRA Moxifloxacin
AMIODAR Amiodarone
AMPLIUM Ampicillin + Cloxacillin
DILZENE Diltiazem
DOLMEN Tenoxicam
DRONAL Alendronate
ESKIM Polyunsaturated fatty acid ethyl esters
ESRADIN Isradipine
FAMODIL Famotidine
GELCLAIR CONCENTRATED
ORAL GEL Polyvinylpirrolidone + Hyaluronic acid + Glycyrrhetinic acid
IVOR Bemiparin
KEPLAT Ketoprofene
LIBRADIN Barnidipine
LIMPIDEX Lansoprazol
LORICIN Ampicillin + Sulbactam
LOSAPREX Losartan
LOSAZID Losartan + Hydrochlorothiazide
LUKASM Montelukast
MIGRAPRIM Lysine acetylsalicylate + Metoclopramide
NAPRILENE Enalapril
NATULAN Procarbazine
NEOPREX Enalapril + Hydrochlorothiazide
NITRO-DUR Nitroglycerine
PROSTIDE Finasteride
Paolo Barbanti The Italian pharmaceutical industry: trends and business opportunities © 81
SINESTIC Budesonite + Formoterol fumarate
SIVASTIN Simvastatin
SPECTRUM Ceftazidime
TALAVIR Valacyclovir
TARGRETIN Bexarotene
TAUXIB Etoricoxib
TENACID Imipenem + Cilastatin
TICLODONE Ticlopidine
TRAXAM GEL Felbinac
TROZOCINA Azithromycin
VIRUXAN Metisoprinol
VSL#3 Milk enzymes
YOVIS Milk enzymes
ZIBREN Acetylcarnitine
LIST OF PRODUCTS BY ACTIVE INGREDIENT
LIST OF PRODUCTS BY ACTIVE INGREDIENT
Acetylcarnitine ZIBREN
Lysine acetylsalicylate +
Metoclopramide MIGRAPRIM
Alendronate DRONAL
Amiodarone AMIODAR
Ampicillin + Cloxacillin AMPLIUM
Ampicillin + Sulbactam LORICIN
Azithromycin TROZOCINA
Barnidipine LIBRADIN
Bemiparin IVOR
Bexarotene TARGRETIN
Budesonite + Formoterol SINESTIC
Paolo Barbanti The Italian pharmaceutical industry: trends and business opportunities © 82
fumarate
Ceftazidime SPECTRUM
Diltiazem DILZENE
Enalapril NAPRILENE
Enalapril + Hydrochlorothiazide ACESISTEM
Enalapril + Hydrochlorothiazide NEOPREX
Etoricoxib TAUXIB
Polyunsaturated fatty acid ethyl
esters ESKIM
Famotidine FAMODIL
Felbinac TRAXAM GEL
Milk enzymes VSL#3
Milk enzymes YOVIS
Finasteride PROSTIDE
Imipenem + Cilastatin TENACID
Isradipine ESRADIN
Ketoprofene KEPLAT
Lansoprazol LIMPIDEX
Losartan LOSAPREX
Losartan + Hydrochlorothiazide LOSAZID
Metisoprinol VIRUXAN
Montelukast LUKASM
Moxifloxacin ACTIRA
Nitroglycerine NITRO-DUR
Polyvinylpirrolidone + Hyaluronic
acid + Glycyrrhetinic acid GELCLAIR CONCENTRATED ORAL GEL
Procarbazine NATULAN
Rivastigmine PROMETAX
Tenoxicam DOLMEN
Simvastatin SIVASTIN
Ticlopidine TICLODONE
Valacyclovir TALAVIR
Paolo Barbanti The Italian pharmaceutical industry: trends and business opportunities © 83
Via Placido Riccardi 19 20132 Milano Italy Tel. ++39-02-45409122 / 27203492 Fax ++39-02-27203492