The pharmaceutical industry in the Centre-Loire Valley … · 15 Bayer DE 16.2 1.9 +26.6 ... Brazil, Russia, Egypt, Pakistan, Romania and ... 8 - The pharmaceutical industry in the

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NOVEMBER 2014

The pharmaceutical industry in the Centre-Loire Valley region(France)

2 - The pharmaceutical industry in the Centre-Loire Valley region 3

FOREWORD

This study, carried out by CENTRECO, the economic development and promotion agency in the

Centre-Loire Valley region (France), focuses exclusively on the pharmaceutical industry. The study

also touches on pharmaceutical production, including contract manufacturing, production of

inorganic and organic commodity chemicals, biopharmaceuticals and R&D companies specialised

in pharmaceutical research.

CONTENTS

CHAPTER 1: The pharmaceutical industry worldwide . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . p. 4

CHAPTER 2: The French pharmaceutical industry . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . p. 8

CHAPTER 3: The drugs industry in the Centre-Loire Valley region . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . p.10

3.1: More than 9,300 jobs in the Centre-Loire Valley region . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . p. 11

3.2: The pharmaceutical industry is more resistant than other industries . . . . . . . . . . . . . . . . . . . . p. 16

3.3: Pharmaceutical products lead regional exports . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . p. 18

3.4: Pharmacy, leading sector for R&D in the Centre region . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . p. 20

3.5 : Training resources in line with the profession’s needs . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . p. 22

3.6: Cluster and prodfessionnal association accompany regional companies . . . . . . . . . . . . p. 24

3.7: Focus on biopharmaceuticals in Centre region . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . p. 25


The landscape of the global pharmaceutical industry has been changing for several years

now, experiencing an historical drop of 1% in the global market in 2012. Nowadays, it is now

a two-tier market, split between the emerging countries whose growth comes essentially from

high volumes, especially in generic drugs, and the developed countries, whose needs

remain great, but who are subject to strong pressure to reduce health expenditure.

France the world's 5th economical power, France plays a major role in the global pharma-

ceutical industry, having long dominated the European production market. In 2014, the

pharmaceutical industry continues to play a significant role in the French economy. It is an

industry which is highly concentrated in geographical terms. Among the 22 regions which

make up the national territory, the Centre region, France's 6th most industrial region,

is one of France's leading regions for pharmaceutical production.

This study on the drugs industry also aims to highlight the new

economic landscape of a sector which places the Centre region at

the top table of European regions in this domain.

Located 1 hour south of Paris, the Centre-Loire Valley region has almost 2.6 million inhabitants spread over the 6 départements which make up the region:

CHER (310,000 inhabitants), capital: Bourges

EURE-ET-LOIR (435,000 inhabitants), capital: Chartres

INDRE (229,000 inhabitants), capital: Chateauroux

INDRE-ET-LOIRE (599,000 inhabitants), capital: Tours

LOIR-ET-CHER (334,000 inhabitants), capital: Blois

LOIRET (666,000 inhabitants), capital: Orléans


1

The pharmaceutical industry worldwide


1

The pharmaceutical industry worldwideThe global pharmaceutical industry has experienced a

major shift in recent years in reaction to upheavals

in the sector. A number of factors including the

dynamic growth of healthcare expenditure in

emerging countries and the needs of developed

countries which remain as great as ever, have

brought about changes in the sector. On the other

hand, other factors have brought about decline:

growing pressure from generics, the political will to

control social deficits, a decrease in R&D produc-

tivity and blockbuster drugs patents falling into

the public domain, among others.

A declining market in 2012

Today, decline seems inevitable for the pharmaceu-

tical industry, which was, however, one of the most

profitable sectors of the last century with double-

digit growth recorded for the period 1999-2003.

In 2012, the global drugs industry decreased by 1%,

generating 856 billion dollars in turnover. The cause

is the loss of patents of blockbuster medicines in

2011 and 2012 in addition to increasingly restrictive

public policies and weakened markets in the United

States and Europe. The strength of the emerging

markets no longer maintains growth of the global

market.

According to rating agency Fitch Ratings, growth

will probably not be restored to the sector before

2015, when the loss of patents protecting a large

number of blockbuster medicines will come to an

end and the leading laboratories will benefit from a

range of new medicines ready for launch, or already

generating profit. Entry into emerging markets will

also benefit the big pharma companies, in order to

return to growth and comfortable margins.

A two-tier global market

The countries where pharmacy and its industries

were born have seen, with a few exceptions, these

industries enter into a prolonged recession, with

their respective markets declining by between

-1% and - 4%. Emerging countries, especially the

BRICS (Brazil, Russia, India, China and South Africa),


THE PHARMACEUTICAL INDUSTRY WORLDWIDE

RANK LABORATORY NATIONALITY TURNOVER 2012*in USD bn

MARKET SHAREin %

CHANGE IN TURNOVER 2011-2012 in %

1 Novartis CH 50.8 5.9 -5.9

2 Pfizer US 46.9 5.5 -18.7

3 Merck & Co US 40.2 4.7 -2.7

4 Sanofi FR 37.7 4.4 +1.9

5 Roche CH 34.8 4.1 -0.3

6 GlaxoSmithKline UK 32.7 3.8 -4.9

7 AstraZeneca UK 32 3.7 -4.8

8 Johnson & Johnson US 27.9 3.3 +14.3

9 Abbott US 26.8 3.1 +19.6

10 Teva ISR 24.8 2.9 +48.5

11 Lilly US 21.9 2.6 0

12 Bristol Myers Squibb US 17.6 2.1 -17

13 Amgen US 17.2 2 +12.4

14 Boehringer Ingelheim DE 17.1 2 +23.9

15 Bayer DE 16.2 1.9 +26.6

TOTAL 444.6 52 + 0.7*Manufacturer's price, medicines sold on prescription

Together, the 15 leading laboratories generate over half of global turnover

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Estimated turnovers 2015 - Change in turnover in the leading markets worldwide between 2010 and 2015 (AAGR1)

+1.5% $357Bn

North America

+12.2% $100.9Bn

Latin America

+7.9% $25Bn

Africa

+12.2% $237BnEuropean

Union

+15.3% $147.1Bn

East and South East Asia

+8.9% $16.7Bn

Oceania

+7.4% $15.4BnMiddle East

+15.3% $27.6Bn

Europe (non-EU)

+15.3% $32.1Bn

India

+3.3% $120.6Bn

Japan


THE PHARMACEUTICAL INDUSTRY WORLDWIDE

on the other hand, have seen their pharmaceutical market

reach levels of growth that developed countries were

experiencing just ten years ago. Pharmaceutical sales in

China, India, Brazil, Russia, Egypt, Pakistan, Romania and

nine other developing countries will continue to grow by

between 13% and 16% a year up until 2015, according to

IMS health.

An industry dominated by the "Big Pharma" companies, with Novartis, Pfizer and Merck on top

According to data from the market research institute IMS Health, Novartis has been the world leader since 2012, with a turnover of USD 50.8 billion. In 2011, the Swiss company was still in second place behind Pfizer, whose turnover has dropped from almost USD 58 billion in 2011 to USD 46.9

billion. The American laboratory has been sharply hit by the loss of exclusive rights to several medicines such as the anti-cholesterol drug Lipitor, the world's best-selling drug with a turnover exceeding USD 10 billion every year.

Nonetheless, although the leading laboratory globally is Swiss, the industry continues to be dominated by American laboratories (7 in the top 15 big pharma companies).

The success of the American industry lies in a number of factors, the main one being the high level of innovation, in addition to significant investment in R&D and close ties between the industry and universities.

1 AAGR: Average Annual Growth Rate


2

The French pharmaceutical industry

The pharmaceutical industry plays an important role in the French economy. In terms of activity and employment, the influence of this industry is stronger in France than in most European countries. It also has a superior average skill

level to that seen in the economy as a whole. However, this historically solid position has recently started to weaken.

The pharmaceutical industry's share in total industrial production, stable since the mid-2000s, has shown slight decline since 2010.

Key figuresJobs 101,900 direct jobs / No.2 in Europe (2011)

Industry 254 sites (2011)

Turnover 52.2 bn euros (2012)

Export 25 bn euros /No.2 French export sector (2012)

R&D expenditure 4.6 bn euros (2010)


The French pharmaceutical market: an unprecedented decline in 2012

In 2012, the French market recorded an historical drop of 2.3% in value (market stagnation in volume). This decline was mainly down to lower prices, the rise in power of generic medicines and the increasing difficulty in bringing out new medicines.

In addition to the boom in generics, which represent 14% of the market in value and 26% in volume, a second major phenomenon characterised 2012 - the dynamic performance of the OTC (Over The Counter) pharmaceutical market. In 2012, 361 million units were sold (+ 3.5%) on the self-medication market, representing a turnover of 1.84 billion euros (+ 7.9%).

More than 52 billion euros in pharmaceuticals turnover in 2012, of which almost half was exported

For a long time, France dominated the production market in Europe, owing to the establishment of industrial sites by leading pharmaceutical groups in the 1980s and 90s, close to their markets. However, the historically solid position of the French

pharmaceutical industry has recently started to weaken.

An export-oriented industry

53% of medicines manufactured in France are exported (an export rate far higher than the rate of the manufacturing industry which is estimated to be around 34%) and in 2013 are, 6% of products exported by France will be pharmaceuti-cal products. With the exception of 2011, French exports of pharmaceutical products grew steadily (+ 5.6% per year on average between 2004 and 2012). This reached a peak in 2013, with over 29 billion euros. Imports are also on the rise, notably of generics. However, imports are increasing faster than exports (+ 7.3% per year on average between 2004 and 2012).

R&D at the heart of pharmaceutical laboratories' strategy

The drugs industry is one of the most research-intensive in-dustries. The total budget dedicated to research is, of course, smaller in absolute value than that of the automotive sector, but it represents a significantly larger percentage of turnover (7% for automotive). Thus, in 2010, 10.2% of total turnover of the pharmaceutical and biotechnology sectors were devoted to R&D, i.e. more than 4.6 billion euros (Leem data). Further-more, research is virtually entirely self-financed by private companies.

Moreover, this investment in R&D is manifested in the existence of seven competitiveness clusters dedicated to pharmacy. Located all over France, these clusters have their own speciality : for examples, Lyonbiopôle (Rhône-Alpes) is dedicated to infectious pathologies and is the cluster of reference for nano-biotechnology. Medicen Paris Region focuses on imaging, cellular and tissue-related medicine and pharmaceutical technologies, while Eurobiomed (PACA- Languedoc-Roussillon) covers laboratories specialised in infectious, tropical and emerging diseases, rare and orphan diseases and neurological pathologies.

An administered industry

The French pharmaceutical industry has one specific feature - since medicine prices are covered by health insurance, they are administered. In summary, the acceptance or reimbur-sement of a medicine depends on the Medical Benefit (SMR) and the Improvement of Medical Benefit (ASMR), assessed by the French National Authority for Health (Haute Autorité de

Santé). Depending on the SMR level (major, important, moderate, weak or insufficient), the medicine will be granted partial or total coverage.

Thus, because of this coverage, medicine prices are not freely set, but are subject to regulation. In the end, medicine prices incorporate shares tied to manufacturers, wholesale distributors and pharmacists.

For several years now, controlling healthcare expenditure has become a priority of successive governments in order to ensure the balance and the longevity of the health insurance system. This priority is reflected in the decision to discontinue subsidising certain drugs, among other measures. Notably, there were several rounds of delisting in 2003, 2006 and 2012.

2

The French pharmaceutical industry

In 2012, the turnover of the pharmaceutical industry on the French market fell by 1.8%

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YEARTURNOVER

FRANCE in billions of euros

TURNOVER EXPORT

in billions of euros

TOTAL TURNOVER

in billions of euros

2000 17,263 9,621 26,884

2005 23,822 16,747 40,569

2010 27,416 24,133 51,549

2011 27,491 22,030 49,521

2012 27,001 25,286 52,287

Service Médical Rendu -

Amélioration du Service Médical Rendu -


3

The drugs industry in the Centre-Loire Valley region

Key figures• Jobs: 9,307 direct jobs / ranked 3rd nationally

• 74% of workforce in companies with over 250 employees

• Establishments: 58 laboratories including 13 contract manufacturing organisations

• Exports: 5.15 bn euros / No.1 regional export sector

• Presence of Polepharma, the French pharmaceutical production cluster

The quality of the region's pharmaceutical sector is reflected by the presence of leading laboratories and also the diversity of the know-how which characterises its pharmaceutical

repertoire (liquids, sterile forms, dry forms, sprays, pastes and semi-pastes, etc.) and dispensing methods, on top of the comprehensiveness of the therapeutic areas

covered by the medicines produced in the Centre region.


3

The drugs industry in the Centre-Loire Valley region

No.3 region in France in terms of jobs

In France, the pharmaceutical industry workforce is princi-

pally located in 3 regions: Ile-de-France, Rhône-Alpes and

the Centre region. With 9,307 employees, the pharmaceutical

industry represents over 7% of regional industrial employment.

The regional territory is suitable for the development of intensive pharmaceutical subcontracting activity. The

CMOs (Delpharm, Chemineau, Famar, Fareva, Synerlab, etc.),

who have sometimes directly taken over their purchasers'

industrial sites, contribute to the development of the sector

and the preservation of industrial jobs. Over 28% of pharma-

ceutical jobs now depend on a subcontracting site.

The leading pharmaceutical laboratory in terms of workforce

is Servier, France's No.1 independent pharmaceutical group,

which has one of the largest pharmaceutical production

sites in France (800 employees), in Gidy in the Loiret dépar-

tement. Since 1996, the site has been home to the Servier

Clinical Support Unit, the biggest unit dedicated to pharma-

ceutical production for clinical trials in Europe. The labora-

tory employs more than 1,200 people in Loiret in total. The

Servier group has 20,000 employees in the world, including

3,000 in the Research and Development sector.

The second-ranked laboratory is the CMO Famar, subsidiary

of the Greek group Marinopoulos, who have two sites in the

Centre region. The first, in the Eure-et-Loir département,

bought from the laboratory Abbott in 2007, specialised in freeze-drying. 200 people are employed there. The second, and biggest, of the CMO's sites, is the Orléans site in the Loiret département, where the laboratory has combined its 2 Orléans sites on the site of the former McNeil Manufacturing factory. The new site has over 700 employees.

Big pharma company Sanofi is the third largest regional employer in the pharmaceutical sector. The group has a site in Indre-et-Loire and a site in Loiret, with a combined workforce of 739 employees.• The Tours site in Indre-et-Loire was inaugurated in 1967

and has been developed in recent years, notably with the installation of a new granulator. The site produces tablets (monolayer, bilayer and trilayer) and capsules (powder and granules), and packs vials and bottles. The site exports 80% of its output to Europe, Asia, Africa, Middle East and

Latin America.

Moreover, since 2008, Tours has been home to Centre of industrial development and innovation and the Central anti-counterfeiting laboratory. • Inaugurated in 1961, the Amilly factory in Loiret is a

cosmetics, pharmaceutical products and chemical products production site which manufactures almost 65 million boxes of dried formula per year.

Lastly, in Chartres, Novo Nordisk owns the only insulin

production unit outside of Denmark and the United States.

Since 1961, this site has been one of the group's strategic

Medicines: flagship activity of the regional pharmaceutical industry

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NUMBER OF ESTABLISHMENTS

NUMBER OF EMPLOYEES

DISTRIBUTION OF EMPLOYEES in %

Manufacture of basic pharmaceutical products 11 504 5.4

Manufacture of pharmaceuticals (human and veterinary medicine) 35 8,277 88.9

- of which contract manufacturing 13 2,645 28.4

R&D 12 526 5,70

TOTAL 58 9,307 100

3.1. More than 9,300 jobs in the Centre-Loire Valley region


sites. The Chartres site is dedicated to the production of 3ml

insulin cartridges. 68% of its output is exported in Europe.

The remaining output is shipped to Oceania and Canada.

Geographical disparities

On the basis of the 58 companies and 9,307 employees, we can

see great geographical disparities in the Centre region's job

pool. The companies of the pharmaceutical sector are, in the

most part, located along the Orléans-Blois-Tours line and near

the boundaries of the Paris region.

The Loiret département alone represents over 39% of the sector's workforce. This département is notably home to

Servier Laboratoires, Pierre Fabre, Sanofi laboratories and the

CMO Famar. As for the Eure-et-Loir département, it constitutes

32.6% of pharmaceutical employment, with, among others,

the laboratories Beaufour-Ipsen, Leo Pharma, Ethypharm and

Expanscience.

The pharmaceutical industry is far less developed in the

départements in the south of the Centre region: Indre and Cher

have only 3 companies and 219 employees.

The pharmaceutical industry is a particularly important industry in the Eure-et-Loir département, where it represents 11.3% of industrial employment and 2.3% of total employment. Is is

also important in Loiret (7.7% of industrial jobs) and Indre-et-

Loire (7.2%).

It should be noted that almost 80% of the workforce is concentrated in 4 employment areas around the cities

of Orléans, Tours, Dreux et Chartres. In the Dreux area, the

pharmaceutical industry represents 27.2% of industrial

employment and 5.4% of total employment.

Pithiviers (Loiret), a mainstay of the fine chemical industry in FranceThe presence of four laboratories - 3M, Isochem, Merck

Estapor and Orgapharm - has made Pithiviers the No.2 fine

chemistry production site in France, behind Mourenx in

the Aquitaine region. This area employs over 300 people.

• American group 3M has one single fine chemistry site

in the world and it has been located in Loiret since

1967. This site's speciality is the production of active

ingredients for the pharmaceutical industry, and more

specifically for 4 families of medicines: cardiology,

urinary antibacterials, analgesics and the stimulation

of immunising defences. More than 50% of output is

exported to Europe, the United States and Japan.

• Merk Estapor, subsidiary of German group Merck, focuses

on the research, development and production of micro-

spheres for in vitro diagnostics, biotechnology and

cosmetics, etc.

• The Loiret unit of Orgapharm, a subsidiary of the Axyntis

group, mainly manufactures two classes of products -

intermediates and active molecules for the pharmaceu-

tical industry and speciality chemicals for the electronics

industry.

• Set up in Pithiviers since 1977, Isochem specialises in

multistage organic synthesis for the pharmaceutical

(over 50% of its turnover), cosmetic and agrochemical

industries. The R&D teams develop around ten new products

a year on the Pithiviers site and around thirty at group

level.

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LES LABORATOIRESSERVIER INDUSTRIE

NOVO NORDISK PRODUCTION SAS

FAMAR ORLEANS

BEAUFOUR IPSEN INDUSTRIE

FAREVA

PROGIPHARM (PIERRE FABRE)

SANOFI WINTHROP INDUSTRIE

SANOFI WINTHROP INDUSTRIE

MERCK SANTE

LABORATOIRES LEO PHARMA

NUMBER OF EMPLOYEES

840 500 250 100 50

SECTORS OF ACTIVITY

Basic pharmaceutical products

Manufacture of medicines

Biotechnology

Pharmaceutical companies located in the Centre region

THE DRUGS INDUSTRY IN THE CENTRE REGION

between them


COMPANY NAME NAT. No. of sites WORKFORCE ACTIVITY

Laboratoire Servier FR 4 1,280 Manufacture of medicines / R&D

Famar Orléans GR 3 925 Contract manufacture and packaging of medicines

Sanofi FR 2 739

- Manufacture of medicines - Fine chemical synthesis unit for pharmaceutical use - Centre of Industrial Development and Innovation (DI&I)- Central anti-counterfeit laboratory

Novo Nordisk DNK 1 730- Manufacture of medicines - Production of insulin

Ipsen Industrie FR 1 580- Manufacture of medicines - Ipsen global centre for pharmaceutical development

Pierre Fabre FR 2 543 Manufacture of medicines

Fareva FR 1 480 Contract manufacture of medicines

Merck Santé DE 1 350Manufacture and contract manufacture of pharmaceutical products for the treatment of diabetes (dry forms)

Laboratoires Leo Pharma

DNK 1 318Manufacture and import of pharmaceuticals (specialist in the manufacture of injectable preparations)

Ethypharm FR 1 310Development and manufacture of medicines with controlled-release of active ingredients

The region's 10 leading companies together employ 67% of employees in the sector

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LOIR-ET-CHER

INDRE-ET-LOIRE

EURE-ET-LOIR

21 3 636

14 1 829

6 584

2 129

1 90

13 3 039

Almost 3 in 4 jobs in the Loiret andEure-et-Loir départements



3 in 4 jobs in companies with over 250 employees

The pharmaceutical industry is an industry with a high

employment rate compared to industry as a whole in the

Centre region. Companies employ 160 people on average,

i.e. an employment rate 8 times higher than that of industry

in the region (some twenty employees).

Moreover, almost 29% of them have over 250 employees,

compared to less than 1% for industry in the region as a whole.

These large companies contain around 74% of the sector's

workforce. It is worth highlighting the fact that 4 companies

have more than 500 employees (2,860 jobs in total).

An industrial fabric which has been completely transformed over the last 10 years

Creations, transfers and disappearances of companies have

changed the region's productive fabric, reflecting the major

restructuring that the pharmaceutical industry has undergone

on a global scale. A few examples of this phenomenon:

• The new Orleans site, in Loiret, of the Greek CMO Famar (who,

up until now, occupied a former Novartis and Sandoz site),

has, since the 1970s, successively been home to laboratories

Parke-Davis, Pfizer and Mc Neil Manufacturing (subsidiary

of the Johnson & Johnson group).

Famar operates on another site in the Centre region, in the

Eure-et-Loir département, which belonged to American

company Abbott up until 2007.

• French pharmaceutical and cosmetic CMO Fareva, who had

already taken over several Pfizer sites in the past, acquired the

Pfizer Indre-et-Loire site in 2013, maintaining the jobs there.

Furthermore, American company Pfizer also committed to

continue sub-contracting the manufacture of its medicines

for 10 years to Fareva.

• Another transfer is that of Novéal Pharma (formerly Biophélia),

specialised in the toll manufacturing of food supplements

and medicines. The laboratory, which employs 86 people,

was taken over by the holding Pharméal in 2013.

• Among the disappearances, BMS (Bristol Myers Squibb),

who in January 2010 closed its site in Eure-et-Loir and

Sinclair Pharma, a specialist in treatments for skin and

mucous membrane conditions, who closed its industrial

unit in Loiret in 2013.

An industry that invests heavily in the Centre region

Two key factors determine, in part, the longevity and deve-

lopment of regional sites:

• the issues related to the site's product portfolio and its

renewal (degree of maturity of products, exposure to generic

competition, degree of export, etc.)

Distribution of companies according to the number of employees, in %

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2013

30,7 % over 500 employees

0,4 % 0 to 9 employees






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Foreign capital

French capital outside

of the region

Centre region capital

n Number of employees n Establishments

Distribution of companies according to their dependence on a group in 2013

16

3 430

5 230

640

27

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• the issues related to the means of production (mastery of tech-

nology, production capacities, dosage forms mastered, etc.).

As such, investment made by the pharmaceutical industry in

new production facilities is particularly noteworthy. On the

one hand, in order to modernise its factories, and on the other

hand, to increase its production capacity or to accommodate

the production of new medicines.

• Thus, French pharmaceutical laboratory Ethypharm launched

an investment programme of 8 million euros in 2013 on its

two production sites in France, one of which is located in

Eure-et-Loir. These new capacities are intended to respond

to the demand for generics, including Esomeprazol, a medi-

cation for the treatment of gastric reflux.

• The Sanofi group invested 15 million euros in 2013 to produce

two medicines in Tours (Indre-et-Loire), which were manu-

factured in the United States, in Kansas City, up till then.

• In October 2013 Innothéra inaugurated its new medicine

packaging unit in Loir-et-Cher. The creation of this industrial

unit, over 90% devoted to medicine exports, was accom-

panied by the recruitment of some forty additional workers

on the site. The new building occupies an area of 5,116 m2

usable space and contains - in addition to packaging work-

shops - new offices, a meeting room, a warehouse, eight air

handling units, a reverse osmosis water treatment plan, etc.

• In late 2012, Chiesi invested 22 million in the installation

of a new building on its site near Blois, in the Loir-et-Cher

département, to house a new production line for one drug.

This medicine comes in a totally innovative form comprising

a double powder of microparticles attached to one lactose

molecule. This process was developed by the group in Italy,

who then decided to extend production to its French site.

COMPANY NAME AMOUNT DESCRIPTION ANNOUNCEMENT DATE

Novo Nordisk €50 MPurchase of new facilities, notably a filling line, an inspection line, formulation, washing and sterilisation facilities, an unloading robot at the beginning of the line and a weighing system for control.

2011

Famar Orléans €30 M Merging of the two Loiret sites on a new site 2011

Expanscience €23 M New 5,000m² HEQ unit for extraction of vegetable active ingredients 2011

Chiesi €22 MConstruction of a new 3,600 m² production module to house the manufacturing of a new drug

2012

Sanofi €15 MNew facilities to accompany the transfer of a part of the production of another of the group's sites

2011

Innothera Chouzy €10 M Construction of a new packaging unit 2012

Laboratoires Leo Pharma

€25 M Rolling out of a sterile syringe line 2010

€10 M Installation of a new aseptic filling line and two new packaging lines 2012

Nypro France €6.5 MExtension of the site to accommodate the manufacture of a new metered-dose inhaler

2010

Famar L’Aigle €6 M Installation of a new filling line and two new freeze-dryers 2010

Wyjolab €5 MOpening of a new production unit and creation of two control and development laboratories

2013

Main investments announced by the regional pharmaceutical industry since 2010

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3.2. The pharmaceutical industry: an industrial sector which is more resistant than other industrial sectors in the Centre region

Financial indicators of the pharmaceutical industry

Financial indicators of the pharmaceutical industry

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10REGIONAL PHARMACEUTICAL

INDUSTRY REGIONAL INDUSTRY

AS A WHOLE NATIONAL PHARMACEUTICAL

INDUSTRY

Margin 23% not provided 31%

Economic rate of return2 10% 9% 17%

Financial rate of return3 11% 8% 18%

Value added rate 47.4% not provided 28.9%

Self-financing rate 159% 115% 266%

Investment rate 15% not provided 12%

Productivity €84,000 per FTE €66,000 per FTE €138,000 per FTE

2 The economic rate of return measures the ability of the company to achieve a result by using all of its means. 3 The financial rate of return measures the ability of the company to remunerate its partners.

Steadily growing up to 2000, employment in the pharmaceutical industry increased considerasly in the Centre region between 2000 and 2005, while industrial employment in the region has been decreasing significantly and steadily since the 1990s.

From 1990 to 2004, the regional pharmaceutical sector

was even more dynamic than the national pharmaceutical

industry, with a significantly higher growth in employment

(for example, + 13.5% in 2004 in the Centre versus + 2% in

France). However, in 2005, the increase in the number of

jobs contracted, stagnating from 2010 onwards.

Production operator posts, owing to the automation of production

lines and production volumes, are overall decreasing in number.

Pharmaceutical sales representatives and preclinical and

clinical development posts are also affected.

Temporary employment picks up in the pharmaceutical industry

Temporary employment is considered a leading indicator

of the development of the labour market. In the event of

an increase, it announces an imminent recovery of stable

employment, and if it falls, it is a sign of companies' uncer-

tainty as to the future of their operations.

Industrial companies in the region have heavily reduced

their use of temporary posts since 2009. 3,900 posts in

total were cut in 2012.

The pharmaceutical industry has not been spared and

the effects of the crisis have also impacted temporary

employment since 2009 (- 14% compared to 2008). However,

the use of temporary positions picked up in 2011 and 2012.

The number of temporary job contracts signed in the region's

pharmaceutical industry totalled 18,478 in 2012, up 1.7% in

a year, versus - 2.2% at national level.

Solid financial results: a successful sector at regional level

Compared to the region's industry as a whole, the pharma-

ceutical industry is a financially more successful sector. It is

more profitable than the region's industry as a whole, with

better economic and financial margins and profitability.

The self-financing rate also shows a greater ability to finance

investments from private funds in the pharmaceutical sector.

The sector also generates more wealth, with higher apparent

productivity than that of the region's industry.

Lastly, the share of equity brought to the balance sheet

shows greater financial autonomy in the pharmaceutical



industry than in the region's industry as a whole (57%

compared to 46%).

Lower salaries in the Centre region that at national level Owing to the high percentage of labourers, (51.2% of regional

pharmaceutical employment compared to 36% at national

level), the remuneration of employees in the pharma-

ceutical industry of the Centre region is significantly lower

than at national level. The average salary is higher that the average salary in regional industry (19,000 euros), but it is significantly lower than the average salary in the French pharmaceutical industry (26,600 euros per year in the Centre region, compared to 32,500 euros in France).

Moreover, although there are fewer management positions,

they are also less well paid in the Centre region (45,200

euros versus 51,800 euros at national level). This is also

the case for the intermediate professions (27,200 euros

versus 30,600 euros).

One in five postes to be replaced by 2022The pharmaceutical industry continues to recruit, notably

to replace retired employees, although the sector is less

affected that the rest of industry: 20% of jobs are filled

by people over the age of 50, versus 25% in industry as

a whole.

Taking into account new conditions for receiving a full-rate

pension, almost 2,000 posts could be freed up by 2022 in

the Centre region, half of which by 2016.


and employers


More than one product in four exported by the Centre region is a pharmaceutical product

In 2013, the Centre region produced almost 18% of national

exports of pharmaceutical products. These exports repre-

sented 27.6% of regional exports. Pharmaceutical exports

are also at the top of the list of products imported by the

region (17.4% of regional imports). They constitute 12.6% of

national pharmaceutical imports.

Although at a much lower level than their long-term average

in 2010 and 2011, exports and imports of pharmaceutical

products have been increasing since 2012. The balance of

trade remains largely positive and stable, at around 2 billion

euros.

Intra-group trade boosts foreign business

In 2013, over 80% of regional laboratories' foreign sales

were made in Europe: Belgium is the No.1 buyer, with more

than 1.8 billion euros of imported pharmaceutical products,

followed by Germany (515 million) and Italy. All the same,

Japan came in 5th place for international sales.

The Centre region buys essentially from European labora-

tories (82.5%). However, imports are less spread out than

exports. Overwhelmingly topping the list of suppliers is Ireland,

who in 2013 supplied over 66% of pharmaceutical products

to the region. Indeed, Irish exports of medicines doubled in

one year. This leadership is explained by the presence in the

country of 18 of the 20 leading pharmaceutical companies

in the world, drawn by the low corporate tax rate. Moreover,

while the country has been hit very hard by the economic

crisis, the pharmaceutical industry creates jobs, invests and

represents more than 50 billion in exports.

The importance of intra-group trade should be noted, i.e. trade between subsidiaries of the same group, which is more substantial in the pharmaceutical industry than in industry as a whole.

3.3. Pharmaceutical products lead regional exports



0

500

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2500

3000

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2013201220112010

Regional trade of pharmaceutical products since 2010, in thousands of euros (not including basic pharmaceutical products)

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The Centre region's main trading partners in 2013

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MAIN CUSTOMERS, in % MAIN SUPPLIERS,

in %66,1 % Ireland

12,5 % United States

5,7 % Germany

3,1 % Italy

2,3 % China

2 % Denmark

1,7 % Spain

1,6 % United Kingdom

0,7 % Belgium

0,5 % Poland

3,8 % Other countries

35,3 % Belgium

10 % Germany

6,1 % Italy

4,1 % United Kingdom

4,1 % Japan

3,9 % Spain

3,6 % Russia

2,3 % Greece

2,1 % Poland

1,8 % Ireland

26,7 % Other countries



The pharmaceutical industry is characterised by the large

amount of R&D activity that it carries out, whether this

be integrated or outsourced. It is the leading sector for

research in the Centre region, representing 1/5th of R&D

expenditure of all of the region's companies.

Outsourcing research

Outsourcing clinical research is a practice which is booming:

the search for savings and the desire to transform certain

fixed costs into variable costs are driving laboratories to

refocus on activities which are considered strategic. Thus,

laboratories devote almost a third of their R&D budget to clinical research outsourcing contracts. CROs - Contract

Research Organizations - are rapidly extending their

influence.

In Baugy, in Cher, where it has 90 employees, the Centre

d’Etudes et de Recherche Biologique (Centre for Biological

Research and Studies - CERB) is a contracted preclinical

research laboratory. It offers the pharmaceutical industry

all of the studies required in toxicology and pharmacology

for entry into phase 1 of clinical trials of new molecules.

The CERB is more specifically specialised in cardiovascular

pharmacology, telemetry, electrophysiology and central

nervous system pharmacology.

As for the CRO Key-Obs, it offers the pharmaceutical industry

testing of molecules with specific animal models, notably for

neurodegenerative diseases and alcoholism. The company

has developed tools for the fine-grain analysis of their

behaviour, their motor function and even their memory. The

laboratory employs 14 people in Orléans in Loiret.

CRO Artimmune carries out research in the fields of allergy

and inflammation. Its activity is mainly oriented towards

respiratory pathologies. With in vivo study models - animal

models of human pathologies and transgenic mice models -

Artimmune offers a scientific consulting service and conducts

studies into immunopharmacology for the pharmaceutical

industry and public research in the field of respiratory

diseases.

Public research

Public research is carried out in the laboratories of the

Universities of Tours and Orléans and at the Orléans branch

of the CNRS (French National Scientific Research Centre).

Research at the Tours Faculty of Pharmacy extends to the

field of medical imaging, biopharmaceuticals, cancerology

and more specifically the study of autism in partnership

with the Inserm (French National Institute for Medical

Research).

Public-private partnerships: The CERs - Centres for Studies and Researchthe CERs were created at the University of Tours in 2005.

Their goal: to link a university laboratory to a regional company to conduct shared research projects. Among the

3.4. Pharmacy, the leading sector for research in the Centre region



Sour

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The public research laboratories (non-exhaustive list)

LABORATORY OF THE UNIVERSITY OF ORLÉANS

ICOAInstitute of Organic and Analytical Chemistry

• Mission: identification of new bioactive models suitable for therapeutic and cosmetic use

TOURS FACULTY OF PHARMACY LABORATORIES

3 INSERM units• Imaging and Brain • Morphogenesis and antigenicity of HIV and Hepatic Viruses • Nutrition, Growth and Cancer

1 INRA unit • Infectiology and Public health

2 CNRS units • Institute for Physiology and Cellular biology • Genetics, Immunotherapy, Chemistry and Cancer

4 laboratories recognised by the Ministry for Research

• Plant biotechnology and biomolecules • Dendritic cells, Immunointervention and Transplants • Nano-medicines and nanoprobes • Therapeutic and molecular innovation

PUBLIC LABORATORIES

CNRS - INEMMolecular and Experimental Immunology and Neurogenetics / Orléans

• Study of respiratory diseases, autism and genetics

CNRS – CBMCentre for Molecular Biophysics / Orléans

• Research into anti-cancer agents and the design of molecular and cellular vectors enabling treatment to be delivered to cells

six existing structures, the CERP is devoted to a niche area:

molecular imaging. A 2.5 million euro project has been set

up with Cyclopharma, a laboratory specialised in nuclear

medicine and radiopharmaceuticals.

Integrated research in laboratories

Major laboratories have chosen the Centre region to develop

their R&D activities:

• In Orléans, Servier laboratories installed their global

platform for galenic and biopharmaceutical innovation

and research in 2008, which employs some fifty researchers,

thus completing the R&D centre already in place, comprising

300 researchers.

The mission of this galenic institute is to study the way in

which to transform an active ingredient into a medicine

and to give it the most suitable and effective format for

patients. It is equipped with technological tools which are

specially designed for the laboratory, such as a computer-

assisted control unit, a powder mixer and high performance

microscopes.

• The Ipsen group's centre of excellence for development

in Dreux brings together two activities - pharmaceutical

development and industrial development. Pharma-

ceutical development acts on chemical and biological

entities and concerns the nature and the substance of

medicines, their mode of manufacture and the method

used to control the manufacturing process. The Dreux

industrial site specialises in the production of oral formats

in sachets and solutions. In 2012, the site produced over

1 billion sachets, 700 million tablets and capsules and 3

million vials.

THE DRUGS INDUSTRY IN THE CENTRE REGIONSo

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Dedicated training courses for the pharmaceutical industry

A great many different roles, and consequently many training

courses, provide access to working in the drugs industry, from

the CAP (Certificate of Professional Aptitude) to the bac+6

(baccelauréat + 6 years' studies) and beyond. In addition to

training courses linked to production, training linked to R&D

and quality are increasingly in demand.

According to the Need for Labour survey carried out by Pôle Emploi (National Agency for Employement), almost 40% of companies in the region had recruitment projects for 2012.

The Centre region is home to several establishments providing

access to training courses for roles in the pharmaceutical

industry, notably the IMT, the FBS France Business School

(formerly Tours ESCEM), the Tours Faculty of Pharmacy and

the CNAM Centre (National School of Engineering and

Technology).

Benefiting from its proximity to major laboratories, the

GRETA Eure-et-Loir has also implemented several training

courses for roles in the pharmaceutical industry.

3.5. Training resources in line with the profession's needs

The IMT, the Institute of businesses and Technologies, one of the main training pools for the national pharmaceutical industryCreated in 1980 in Tours (Indre-et-Loire), the IMT Group

is today the leading centre in France in the field of training

for roles in the Health Industries (pharmaceuticals and

cosmetics). Its training courses go from level V (CAP) to

level II (Bac+3).

The posts of technical operator (OTPCI), technician (TPI)

and advanced technician (TSPI) in industrial pharmacy

and cosmetics are available in on-going training and by

the VAE (Validation of Prior Experience). Since September

2010, a new level II training course (Technician Specialised

in Industrial Bioproduction) has been offered, and since

2013, a new training course in maintenance (TSMEB) has

been available.

The IMT Group also offers courses which lead to qualifi-

cations, falling within the Forward Planning of Employment

and Skills (GPEC), and accompany the professional deve-

lopment of employees of pharmaceutical, cosmetics and

veterinary companies.

Its fields of expertise are quality (BPF, FDA, ISO, procedures,

qualification), quality control, logistics, production (dosage

forms, manufacturing process, packaging) and maintenance

(heats attendant, metrology training).



Training courses devoted to heath care biotechnology

In the Centre region, there are several training courses

specifically focussing on the study of biotechnology:

• The IMT, the Institut des Métiers et Technologies (Insti-

tute of Occupations and Technologies), offers a Technician

Specialised in Industrial Bioproduction (TSBI) training

course accessible for people with a scientific Bac+2 or who

can provide proof of equivalent professional experience.

• The Lycée Jacques Monod, in Loiret, offers a Biotechno-

logy BTS which enables the graduate to work in either

research or production. The technician applies biological,

biochemical and biophysical techniques to produce

substances which can be used in the pharmaceutical,

cosmetics or agri-food businesses.

• The Lycée d’Enseignement Général et Technologique

Agricole (LEGTA) in Vendôme (Loir-et-Cher) offers a BTSA

Anabiotech (agricultural, biological and biotechnological

analyses) which trains advanced laboratory technicians

over two years.

• The Lycée Grandmont de Tours (Indre-et-Loire) offers

a Bac STL - Biotechnology: the activities and teachings

dispensed are linked to the biotechnology sector and

focused on industrial production (agri-food, pharmaceu-

tical, cosmetic), services (health, research, water quality,

bio-industrial quality), and environment (health, ecology).

The University of Tours offers a Masters in Biology, health,

Food, specialism "Biotechnology and law", which has the

special feature of being directed at two categories of

students: legal practitioners and scientists. These students

gain further knowledge enabling them, for example, to

prepare patent applications or to manage the regulatory

element of biotechnological activity.

As for the University of Orléans, it offers two Biological

sciences Masters - Specialism Biochemistry-Molecular

biology and Biotechnology, one intended for professionals

and the other for research purposes.

The Bio3 Institute: a new training body in 2015Launched by the government, the Universities of Tours and

of Orléans, the IMT Group and the CROUS (Regional Centres

for University and School Affairs), the Bio3 Institute will be

dedicated to work-linked training courses for production

roles for biopharmaceuticals and biocosmetics. It is the

only project in France which exclusively focuses on training

in bioproduction, biocontrol and bioregulation of pharmaceu-

tical and cosmetic products produced by biotechnology.

Production, research, maintenance, regulation, etc. the

Bio3 Institute will deal with biotechnologies and cosmetic

bioactives in all their forms. 20 innovative training courses

with a focus on apprenticeships will be offered.

The Bio3 Institute will be set up on the new Tours university

site in Indre-et-Loire.


, and named up until re-

cently French Institute for

Cosmetic bioactives and

Biopharmaceuticals (IFBC)


The Centre region benefits from the presence of a profes-sional association, the GRÉPIC, and a national pharmaceutical production cluster, Polepharma.

Created in 1981, the GRÉPIC, Regional Grouping of Industrial

Pharmaceutical Establishments of the Centre region, plays

an organisational and uniting role in the pharmaceutical

sector in the Centre region. Based in Indre-et-Loire, the

Association under Law 1901 covers the Centre region and

also the neighbouring départements (Maine-Loire, Sarthe,

Yonne and Nièvre). It has some fifty members (pharma-

ceutical laboratories, CMOs, depositories, etc.).

Each year, the GRÉPIC, along with the LEEM4 and the ANSM5,

organises the Printemps de la Production Pharmaceutique

(Spring of Pharmaceutical Production) in partnership with

the IMT. These events now feature among the most important

dates of the year for the profession.

Polepharma, the national pharmaceutical production cluster

Created in 2002, Polepharma unites more than 160 members:

pharmaceutical laboratories, suppliers throughout the value

chain (from chemistry to distribution), training centres,

Universities, R&D centres, etc. Located in 4 regions (Centre,

Haute and Basse Normandie and Ile-de-France), Pole-

pharma is the leading pharmaceutical production basin

in Europe, representing almost 30,000 jobs and 53% of

pharmaceutical production in France.

The cluster's role is to stimulate the economic and industrial

development of players in the pharmaceutical sector by

means of measures promoting Competitiveness, Inno-

vation and Dynamism of the Network (cross-visits between

laboratories and suppliers, professional clubs and joint

stands at international reference fairs with the support of

Centréco). Made legitimate by its regional presence and how

representative it is, Polepharma is a source of proposals to

public authorities in terms of industrial health policy.

3.6. Cluster and professional association accompany regional companies

4- LEEM: French Federation of Pharmaceutical Companies5- ANSM: National Medicines Safety Agency



The Centre region is home to 15 establishments specialising

in health care biotechnology, and also establishments specia-

lising in various industrial domains, notably environmental

protection and the agri-food sector.

Among them is Glycodiag which has 7 employees in Chevilly

in Loiret. The start-up, which has a platform dedicated to

applied glycoanalysis, operates in various fields - pharma-

ceutical, cosmetic and veterinary research, the agri-food

sector, and the environment. Its technology is used to

discover new therapeutic models and new markers.

Bertin Pharma, subsidiary of Bertin technologies, offers

services including the formulation of drugs, their evolution

in the body, the analytical development of investigational

medicines, as well as the manufacture of assay kits for

bioanalysis.

As a reminder, in 2008, the company bought the Orléans

(Loiret) company Biotec Centre, specialised in clinical

studies and pharmacokinetic, metabolism and bioanalysis

services.

Set up in Tours, the biotechnology business VitamFero

specialises in antiparasitic vaccinology. It notably designs

new veterinary vaccines for the prevention of ovine toxo-

plasmosis. Created in 2005, and acknowledged the same

year at the French National Innovative Business Creation

Competition, Vitamfero (10 employees) is currently working

on several projects in animal health and also in human

health. The company has many R&D partnerships with,

among others, British company Imaxio, Canadian company

Sirona Biochem and Merial, the biotech division of Sanofi.

In regard to production establishments, very few are oriented

towards the manufacture of biotechnology products. These

include Novo Nordisk (insulin), Recipharm (recombinant

hormone) and Leo Pharma (heparin). However, it should be

noted that these establishments do not manufacture active

ingredients, but package them.

Research of the CBM focussed on biological macromolecules

The CBM, Centre for Molecular Biophysics, is an intramural

unit of the CNRS, contracted with the University of Orléans.

It was founded in 1967 to set up collaboration between

chemists, biologists and physicists, with a research focus

on understanding the specific properties of biomacromo-

lecules. Its researchers seek insight into the structure,

dynamics and interactions of biomacromolecules, at

different levels: in vitro, in silico, in cellulo and in vivo. 130

people contribute to the various projects on DNA repair,

proteins linked to immunology and the structure of mole-

cules of living things.

3.7. Focus on biopharmaceuticals in the Centre region


2726 - The pharmaceutical industry in the Centre region

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CENTRECOEconomic development and promotion agency for the Centre-Loire Valley region37 avenue de Paris

45000 Orleans – France

Tel.: +33 – (0)238 79 95 40

Email: [email protected]

Websites: www.centreco.regioncentre.fr /

www.investinloirevalley.com

Documents

The pharmaceutical industry in the Centre-Loire Valley … · 15 Bayer DE 16.2 1.9 +26.6 ... Brazil, Russia, Egypt, Pakistan, Romania and ... 8 - The pharmaceutical industry in the