Nowadays patients and physicians can have access to three types of drugs: a originators, a generic or a biosimilar. Those drugs have different regulatory systems that apply in Europe; moreover the biosimilars regulation is evolving and may change. Regulation is an important factor that can give more confidence to patients and healthcare professionals. As a consequence, biosimilaires will grow.

1. Masters of Science in International Strategy and Influence
SKEMA Business School, School of Knowledge Economy and Management
France, China, United States and Brazil
REGULATORY ISSUES ON THE DEVELOPMENT OF
BIOSIMILARS
Research Question:
Which regulatory framework could foster the market development of biosimilars
in Europe? And which strategic positioning for the originators
manufacturers?
Student: Joseph Pategou
Tutor: Healthcare expert at Boston Consulting Group
Co-Tutor: Dr. Benjamin LEHIANY, Research Associate Polytechnic School Paris and
Scientific Director, MSc. International Strategy & Influence
Year: 2014 – 2015

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TABLE OF CONTENT
Acknowledgement ............................................................................................................................3
Executive summary ..........................................................................................................................4

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ACKNOWLEDGEMENT
I want to thank all those who gave me their help and their support during my
scholarship and in the preparation of my graduation memory.
First, I want to thank in France, the LEEM, the GEMME, the Association France
Colon, the Maison des MICI, the French Society of Cardiology, the French Society of
Rheumatology, the French National Society of Gastroenterology and IMS Paris for their trust
and availability.
In Great Britain, I thank the Medicines and Healthcare Products Regulatory Agency,
the Association of the British Pharmaceutical Industry, National Institute for Health and Care
Excellence, the British Society for Rheumatology and IMS London for their support and
availability.
I want to thank the Italian Federation of Cardiology, the Confederation of the three
Italian Societies of Gastroenterology and the European Federation of Crohn's & Ulcerative
Colitis Associations for their valuable assistance on regulation in Italy.
I am grateful to the Drug Commission of the German Medical Association and the
German Society of Rheumatology.
Thanks to the European Medicines Agency, European Generic Medicines Association
and European Biosimilars Group for the incredible support they have given me in the
realization of this research.
I express my gratitude to Professor Benjamin Lehiany and the Boston Consulting
Group for allowing me to work on this exciting subject.
My sincere acknowledgment to my family for their encouragement.
I also wish to thank the teaching staff of Skema Business School for the teachings and
support.

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EXECUTIVE SUMMARY
Nowadays patients and physicians can have access to three types of drugs: a
originators, a generic or a biosimilar.
Those drugs have different regulatory systems that apply in Europe; moreover the
biosimilars regulation is evolving and may change. Regulation is an important factor that can
give more confidence to patients and healthcare professionals. As a consequence,
biosimilaires will grow.
Therefore the question we shall ask ourselves is
Which regulatory framework could foster the market development of biosimilars in
Europe? And which strategic positioning for the originators producers?
To bring the most accurate answer to this question, we will study the regulation
framework in France, Germany, Italy and United Kingdom.
I. METHODOLOGY
To understand the regulatory issues on the development of biosimilars in France,
Germany, Italy and United Kingdom:
We first determined the main differences between generics and biosimilars using mainly
secondary data, focusing on regulation and market trends.
Then, we concentrated on regulation of biosimilars, by doing 22 interviews of 4 types of
organizations (Authorities, National and European pharmaceutical unions, Learned Societies
and patient associations); we established a questionnaire of 10 questions based on five main
topics:
 Naming  Labelling
 Clinical trials /extrapolation  Switching/ substitution
 Quotas/ tenders
All interviewees received the same questions; we made cross analysis between countries and
actors in order to draw the best lessons.
Finally, we looked which strategic positioning could have a originators producer to face
biosimilars and to maintain its position in the market by studying 13 companies.

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II. EMPIRICAL CONTEXT : COMPARISON BETWEEN
GENERICS AND BIOSIMILARS
Biosimilars and generics are drugs which enter the market at the end of the originators
patent; our observations help us to see the main differences in terms of regulation and market
trends between these two types of drugs.
Generics have simple chemical structures and are considered to be identical to their
reference medicines. In comparison, a medicine which is developed to be similar to an
existing biological medicine is a biosimilar (see table 19).
Table 19: Comparison of difference and common points between biosimilars and generics-
Structure
KEY POINTS BIOSIMILARS GENERICS
Nature Drug extracted from a biological
environment
Chemical drug
Molecular size Up to 270,000 Da 100 to 200 Da
Development Comparative studies Bioequivalence studies
Duration of development 5-7 years(500 patients) 2-3 years (20-50 patients)
Cost of the development 200-300 million dollars 2-4 million dollars
On regulation, we observed dissimilarity, for example the Marketing Authorization of
generics is mainly based on bioequivalence studies or for biosimilars on comparative study
(see table 7).
Table 7: Comparison of difference and common points between biosimilars and generics-
Regulation
KEY POINTS DIFFERENCE IDENTICAL
Naming
x
Labelling x
Substitution x
Quotas and tenders x
Marketing authorization x
Moreover, biosimilars regulation is part of important debates in many countries,
compared to generics drugs.

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Eight major world markets accounting for 84% of their global sales drive the generics
(United States, Germany, France, Britain, Canada, Italy, Spain and Japan). The first market is
the United States with 42% of global sales (global sales $123.85 billion in 2010 and will reach
$231.00 billion in 2017).
When you talk about biosimilars, the EU is the most advanced market, accounting for
80% of global spending (Global market: $2.6 billion in 2016 to $25 billion in 2020). We
observed 19 biosimilars in Europe representing 6 actives substances. In terms of volume and
value, Germany is the largest; followed by France, Italy and the United Kingdom.
All these elements clearly show us that between these two drugs we have different
market trend (see table 13)
Table 13: Comparison of difference and common points between biosimilars and generics-
Market trend
KEY POINTS DIFFERENCE IDENTICAL
The leading countries x
Market value x
Number of product x
Production cost x
III. RESULTS AND ILLUSTRATION
Those 22 interviews we made helped us understand the position of Authorities,
National and European pharmaceutical unions, Learned Societies and patient associations in
four European countries (France, Germany, Italy and the United Kingdom).
On a topic like naming, the role of regulation, substitution, market shares, price
evolution of the originators and biosimilars, we have a global consensus between actors.
Positions are more variable between actors on regulatory issues such as summary of
product characteristics, interchangeability and extrapolation.
We made an historical benchmark of 13 companies from 2000 to 2015. And observed
10 levers, which were taken by originators manufacturers facing biosimilars and generics
competition.

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 Price  Prescription
 Patent  Market saturation
 Legal action  New market
 Cooperation  Environmental strategy
 Product  Brand strategy
Some of these levers seem to be used in the context of biosimilars and others in presence of
generics (see table 18).
Table 18: Comparison of levers used by originators producer to face biosimilars and generics
competition
Levers Biosimilars Generics
Price X X
Patent X X
Legal action X X
Cooperation X X
Product X X
Prescription - X
Market saturation - X
New market X -
CONCLUSIVE DISCUSSION
The research on France, United Kingdom, Italy and Germany allows us to understand
the regulation of biosimilars and the issues regarding this new type of drug.
One of the lessons is the fact that the regulation of biosimilars is not clear and still in
discussion in many countries, on topics like naming, role of regulation, substitution, summary
of product characteristics, extrapolation and interchangeability.
Our interviews helped us to have a clear vision on those topics:
For the naming system, the World Health Organization suggests a four-letter code
attached at the end of every drug name.

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Concerning the label (SmPC) of a biosimilar, it must be in concordance with the label
of the reference product.
In term of extrapolation, biosimilars have the possibility to be used in several
indications like the reference product.
Regarding the substitution of biosimilars by pharmacists, there is a global consensus
on the fact that it is impossible and not allowed at the moment. But in some countries
discussions are in place to allow substitution by pharmacists, for example in France.
One of the hottest topics on biosimilar regulation, interchangeability is still in
discussion. Germany and United Kingdom have accepted the principle of interchangeability
unlike Italy and France who have refused this principle.
The economic situation in OCDE countries is an important element that biosimilars
and originators manufacturers need to bear in mind. Due to the economic crisis, the total
spending of health is declining since 2009 in several countries.
According to the Panorama health 2013 of the OECD, it is essential in this context that
countries make their health systems more productive, more efficient and more affordable.
The countries have sought to reduce spending by lower prices of medical goods,
particularly pharmaceuticals, and by budgetary restrictions and wage cuts in the hospital
sector.
For example, in France and Germany the costs in percentage of GDP evolved from
10% to 12% between 2000 and 2008, then decreased to reach 11% of the GDP in 2011.