DEMO’s investment in Biotechnology – Development and Production of Monoclonal Antibodies

1. 11th Clinical Research Conference
DEMO’s investment in Biotechnology
–
Development and Production of Monoclonal Antibodies
Γιώργος Βαρδαμίδης
Quality Assurance Manager
Biotechnology Operations

2. Contents
DΕΜΟ Pharmaceutical
Investments of DEMO in Biotechnology
Biological Pharmaceutical Products
Manufacturing Process of Monoclonal
Antibodies (mAbs)
Bio - Academy
Biosimilar Development and Clinical
Studies

3. 1
2
3
Specialized in the Development
and Production of Injectables
Ranked #1 in hospital sales in Greece
(in terms of sold units)
Ranked #1 in exports of branded products
Ranked #1 in production facilities for injectables

4.  4 Manufacturing Plants
 25 Production Lines
 20 Packaging Lines
 The first manufacturing plant in Greece filling injectables in plastic ampoules
 The largest pharmaceutical manufacturing complex of Southeastern Europe with a global reach
Total area exceeding 66.000m2

5. New Countries 2021: Νepal, Paraguay
78,8%
Of the company’s annual production
is exported to international markets
“Active” in 96 countries as of 31.5.2016
Own branded products in 85 countries
2.926 approved products,
527 products under approval

6. Internationally Recognized
Quality Accreditations
• Officially Approved Supplier of the United Nations, UNICEF,
World Health Organization, Medicines Sans Frontiers, International Co
mmittee of the Red Cross
• Approved by PIC/s countries (Europe, Switzerland, Canada, Australia)
• Approved by the Korean-FDA
• Approved by Brazilian Drug Agency (ANVISA)
• Approved by GCC (Health Minister’s Council for Cooperation
Council States) – Gulf countries
• Many other health authorities of non-EU countries
(China, Jordan, South Africa MCC, Egypt, Turkey, Yemen, etc)
EU cGMP certified (current Good Manufacturing Practices)
ISO-9001, ISO-13485, ISO 14001:2015, ISO 45001:2018

7. 1.214 Employees
*December 2022
53% 47%
0
200
400
600
800
1000
1200
2011 2012 2013 2014 2015 2016 2017 2018 2019 2020 2021 2022
963
928
1.025
1.214*
As a result of expansion in new markets along with the investments performed
during the last decade DEMO has created and keeps creating job openings and
career opportunities

8. NEW INVESTMENT PLAN 2021-2027: 356 million €
1. State of the art facility for the development of monoclonal antibodies and a BioAcademy, Attica
2. 4 units for the production of raw materials and 6 units to produce final products, Tripoli
3. Modern R&D laboratories, Thessaloniki
4. Expansion of production in Krioneri, Attica

9. Fully equipped with state of the art production scale
machinery and instrumentation
Total Area > 2.000 sq.m.
1 Fully Trained Personnel
Continuous recruitment of Scientists
Collaboration with Academia
2
State of the Art Pilot plant to produce
biopharmaceuticals

10. Fully equipped with state of the art lab scale machinery
and instrumentation
Total Area > 1.000 sq.m.
1 Fully Trained Personnel
Continuous recruitment of Scientists
Collaboration with Academia
2
State of the Art R&D and
QC Laboratories

11. Biologic Drugs
• Biotechnological drugs, also known as biological drugs, are a special category of drugs that are made exclusively from
living organisms in contrast to conventional small molecule drugs which are chemicals that can be produced through
chemical synthesis.
• Monoclonal Antibodies :
• Able to recognize and attach to specific antigens
• Able to circulate in plasma for long time

12. Development and Manufacturing Process of mAb​
OVERVIEW​
Cell Line Develo
pment and Cell
Banking
Process Develo
pment
Manufacturing Fill & Finish
Analytical Analytical

13. Bioprocess Flow Diagram

14. Pharmaceutical Features​ Questions to Answer​
Identity​ Is the Protein that I have the one I want ?​
Content/​
Purity​
How much Target Protein is there?/ What else is there and in what Quantity ?​
Activity​
How active is the product with regard to a defined pharmaceutical property in
the biological system ?​
Appearance​ What does the product look like ?​
Stability​
How do these five preceding parameters change time or varying physical
conditions ?​
Biosimilarity​ All the above tested in comparison to the reference product​

15. QC Batch Release Assays
Safety Bioburden
Safety Endotoxin
General Appearance (colour and clarity)
General pH
General Concentration
Identity Peptide Mapping
Identity IEF/cIEF
Purity SDS-PAGE/CE-SDS
Purity SEC-HPLC
Potency Cell Based Assay
Potency Antigen Binding
Impurities HCP
Impurities Residual Protein A
Analytical Methods – Quality Control

16. Fully equipped with state of the art lab scale machinery
and instrumentation
Total Area > 1.000 sq.m.
1 Recruitment of new scientists from Universities and
training on the production of biologics under GMP
Collaboration with Academia
2
Establishment of Bio - Academy

17. Biosimilar Development and Clinical Studies
Source: European Medicines Agency
• Biosimilar Development is comparative and
progresses in a step – wise manner.
• In vitro studies compare the protein structure
and biological function between the biosimilar
and its reference medicine.
• The non-clinical and clinical data needed to
approve a biosimilar are different from those
needed for a biological medicine with a new
active substance.
• By demonstrating biosimilarity, the biosimilar
relies on the safety and efficacy experience
gained with the reference medicine.

18. Biosimilars Are Not Generics
Biosimilars and generic drugs are both versions of original brand-name medicines that may offer patients more affordable
treatment options. There are, however, important differences:
• Generic drugs are usually chemically
synthesized while biological products,
including biosimilars, are generally
manufactured from living sources.
• Because the active ingredients of generic
drugs generally are smaller and simpler,
they are usually easier to copy.
• Biologics generally cannot be copied
exactly, because the product (e.g.,
monoclonal antibody) contains a mix of
many slight variations of a given protein
that occurs during its production from
living sources, which introduces inherent
variation.
FDA Level 1_Slides_Foundational Concepts_v3

19. Our Ιmpact
New Pilot Plant and R&D facilities dedicated for the development
and manufacturing of biopharmaceuticals
DEMO SA will invest 100 million € in the next 10 years for the
development and production of monoclonal Antibodies (Biosimilars)
produced in mammalian cell lines
New Job Openings including High Skilled Professionals
Contribution to Brain Gain
Aim to enhance Collaboration with Academia in Greece
Need for Clinical Studies for the mAbs which will be developed and
produced at the DEMO facility.

20. Thank you!