Pharmaceutical medicine
Si-Jin van de Vorst
Contents
Introduction ........................................................................................................................................... 3
Drug design and discovery - D. Copmans ........................................................................................... 4
High throughput screening – part 1 ..................................................................................................... 5
Hit to lead – part 2 ............................................................................................................................... 7
Pharmaceutical development - G. Van den Mooter............................................................................ 9
Clinical drug development – J. De Hoon ........................................................................................... 15
Part 1 ................................................................................................................................................. 15
Part 2 ................................................................................................................................................. 17
Part 3 ................................................................................................................................................. 18
Part 4 ................................................................................................................................................. 22
Part 5 ................................................................................................................................................. 23
Special populations (top-down)– K. Allegaert .................................................................................. 25
Pharmacometrics ................................................................................................................................. 28
PBPK (bottom-up)- P. Annaert .......................................................................................................... 28
MIDD- E. Dreesen ............................................................................................................................ 29
Guidelines and regulations in clinical research- J. De Hoon ........................................................... 31
Small molecules and biologicals- D. Bamps ...................................................................................... 32
Vaccine development- L. Delang ........................................................................................................ 35
Regulation concerning MA- M. Casteels ........................................................................................... 38
Regulatory authorities for registration (MA/VHB) ........................................................................... 38
Process of MA – role of national agencies in the EU/EMA .............................................................. 38
CTD – Common Technical Document .............................................................................................. 39
Definition of innovation? .................................................................................................................. 39
Orphan medicines and “orphan designation” .................................................................................... 39
Recent evolutions: CMA–AT–RMP .................................................................................................. 39
Marketing and risks ........................................................................................................................... 40
Pharmacovigilance- K. Sierens and I. Spriet .................................................................................... 40
Pre-registration/GCP-requirements ................................................................................................... 40
Data Safety Monitoring Board (DSMB) ........................................................................................... 41
Post-registration................................................................................................................................. 42
Reimbursment- F. Arickx.................................................................................................................... 43
Drugs and society- I. Spriet ................................................................................................................ 45
Part I .................................................................................................................................................. 45
1
, Part II ................................................................................................................................................. 46
Medical Department- D. Vander Mijnsbrugge ................................................................................. 48
Closing remarks ................................................................................................................................... 49
2
,Introduction
EMA (European Medicines Agency) or FDA (Food and Drug Administration, USA) give
recommendations for authorisation of new medicines.
• PRIME= priority medicine
o Medicines with high unmet need
o Quicker approval/review
• Orphan medicine
o Treat certain rare medical conditions
• ATMP= Advanced Therapy Medicinal Product
• Biosimilars versus generics
The types of medicines approved have changed over the years:
• 1st wave small molecules
o Screen large numbers of compounds
o Defined chemical synthesis and identical copies can be made
o Relatively simple and well-defined and stable
o Cave: off-target effects/toxicity
o E.g. statins
• nd
2 wave Biologicals
o Produced through biotechnology in a living system where the active substance is
derived from
o Large complex molecules
o Designed for target
o Fewer off-target effects, but risk of anti-drug antibodies
o E.g. PCSK9-inhibitors
• rd
3 wave oligonucleotides
o Genetic medicine
o Treats/modulates underlying cause
o Included siRNA, gene therapy, etc.
o Often rare diseases/genetic causes
o E.g. ATMPs
Drug life cycle
FIH test (first in humans) to go from preclinical to clinical. To go to clinical, they need to be approved
by Investigational New Drug (IND, USA) or Clinical Trial Application (CTA, EU). Submit protocol
3
, and info into Clinical Trial Information System (CTIS, made by EMA) and go to the ethics
committee and local Competent Authority.
For approval for marketing, they need to submit a Common Technical Document (CTD) to show the
risk/benefit of the drug. Additionally, they submit a Marketing Authorisation (Application) (MA,
EU) or New Drug Application (NDA, USA).
When approved, reimbursement and commercialisation are the next steps. Reimbursement depends on
how much the country is willing to pay.
Throughout the whole process, the quality standards, guidelines, ethical standards and regulations
need to be followed.
Drug design and discovery - D. Copmans
Before a study starts, it will ask three questions:
• Strategically: Is it desirable to do?
• Scientifically/technically: Can it be done?
o Models, (validated) targets?
o Compounds? Patents?
o First-in-class, fast follower, best-in-class, me-too?
▪ First class=certain target (first drug)
▪ Fast follower= second or third drug for a certain target → turns into me-too
drug
▪ Best-in-class= is better than the current drugs for a certain target
• Operational: Can we do it?
The clinical situation is often a clear and detailed picture, but non-clinical proxy is often distorted and
does not always resemble the clinical situation. To have the most accurate picture, different models are
developed.
Thus, the aim of drug discovery and design is to identify pharmacologically active molecules for
which there are clear indications and that will reach the target in sufficient amounts to exert their
desired effect without toxicity.
4
Si-Jin van de Vorst
Contents
Introduction ........................................................................................................................................... 3
Drug design and discovery - D. Copmans ........................................................................................... 4
High throughput screening – part 1 ..................................................................................................... 5
Hit to lead – part 2 ............................................................................................................................... 7
Pharmaceutical development - G. Van den Mooter............................................................................ 9
Clinical drug development – J. De Hoon ........................................................................................... 15
Part 1 ................................................................................................................................................. 15
Part 2 ................................................................................................................................................. 17
Part 3 ................................................................................................................................................. 18
Part 4 ................................................................................................................................................. 22
Part 5 ................................................................................................................................................. 23
Special populations (top-down)– K. Allegaert .................................................................................. 25
Pharmacometrics ................................................................................................................................. 28
PBPK (bottom-up)- P. Annaert .......................................................................................................... 28
MIDD- E. Dreesen ............................................................................................................................ 29
Guidelines and regulations in clinical research- J. De Hoon ........................................................... 31
Small molecules and biologicals- D. Bamps ...................................................................................... 32
Vaccine development- L. Delang ........................................................................................................ 35
Regulation concerning MA- M. Casteels ........................................................................................... 38
Regulatory authorities for registration (MA/VHB) ........................................................................... 38
Process of MA – role of national agencies in the EU/EMA .............................................................. 38
CTD – Common Technical Document .............................................................................................. 39
Definition of innovation? .................................................................................................................. 39
Orphan medicines and “orphan designation” .................................................................................... 39
Recent evolutions: CMA–AT–RMP .................................................................................................. 39
Marketing and risks ........................................................................................................................... 40
Pharmacovigilance- K. Sierens and I. Spriet .................................................................................... 40
Pre-registration/GCP-requirements ................................................................................................... 40
Data Safety Monitoring Board (DSMB) ........................................................................................... 41
Post-registration................................................................................................................................. 42
Reimbursment- F. Arickx.................................................................................................................... 43
Drugs and society- I. Spriet ................................................................................................................ 45
Part I .................................................................................................................................................. 45
1
, Part II ................................................................................................................................................. 46
Medical Department- D. Vander Mijnsbrugge ................................................................................. 48
Closing remarks ................................................................................................................................... 49
2
,Introduction
EMA (European Medicines Agency) or FDA (Food and Drug Administration, USA) give
recommendations for authorisation of new medicines.
• PRIME= priority medicine
o Medicines with high unmet need
o Quicker approval/review
• Orphan medicine
o Treat certain rare medical conditions
• ATMP= Advanced Therapy Medicinal Product
• Biosimilars versus generics
The types of medicines approved have changed over the years:
• 1st wave small molecules
o Screen large numbers of compounds
o Defined chemical synthesis and identical copies can be made
o Relatively simple and well-defined and stable
o Cave: off-target effects/toxicity
o E.g. statins
• nd
2 wave Biologicals
o Produced through biotechnology in a living system where the active substance is
derived from
o Large complex molecules
o Designed for target
o Fewer off-target effects, but risk of anti-drug antibodies
o E.g. PCSK9-inhibitors
• rd
3 wave oligonucleotides
o Genetic medicine
o Treats/modulates underlying cause
o Included siRNA, gene therapy, etc.
o Often rare diseases/genetic causes
o E.g. ATMPs
Drug life cycle
FIH test (first in humans) to go from preclinical to clinical. To go to clinical, they need to be approved
by Investigational New Drug (IND, USA) or Clinical Trial Application (CTA, EU). Submit protocol
3
, and info into Clinical Trial Information System (CTIS, made by EMA) and go to the ethics
committee and local Competent Authority.
For approval for marketing, they need to submit a Common Technical Document (CTD) to show the
risk/benefit of the drug. Additionally, they submit a Marketing Authorisation (Application) (MA,
EU) or New Drug Application (NDA, USA).
When approved, reimbursement and commercialisation are the next steps. Reimbursement depends on
how much the country is willing to pay.
Throughout the whole process, the quality standards, guidelines, ethical standards and regulations
need to be followed.
Drug design and discovery - D. Copmans
Before a study starts, it will ask three questions:
• Strategically: Is it desirable to do?
• Scientifically/technically: Can it be done?
o Models, (validated) targets?
o Compounds? Patents?
o First-in-class, fast follower, best-in-class, me-too?
▪ First class=certain target (first drug)
▪ Fast follower= second or third drug for a certain target → turns into me-too
drug
▪ Best-in-class= is better than the current drugs for a certain target
• Operational: Can we do it?
The clinical situation is often a clear and detailed picture, but non-clinical proxy is often distorted and
does not always resemble the clinical situation. To have the most accurate picture, different models are
developed.
Thus, the aim of drug discovery and design is to identify pharmacologically active molecules for
which there are clear indications and that will reach the target in sufficient amounts to exert their
desired effect without toxicity.
4
