PHARMACEUTICAL MEDICINE
1. INTRODUCTION
DEFINITION
Medical discipline = speciality for medical doctors
→ includes discovery, development, evaluation registration, monitoring and medical
aspects of marketing of medicines for the benefit of patients and the health of the
community.
Pharmaceutical medicine is responsible for ensuring and maintaining standards in the
discipline and curriculum for higher medical training to equip specialists with the
comprehensive skills and competence increasingly demanded by the industry for the
public good
AUTHORIZATION & ADMINISTRATION OF DRUGS
EMA = European medicines agency
→ authorization for new medicines
In the last decade, the total number of drug approvals has generally increased, with some
peak years
→ most approvals are new molecular entities (NMEs)
PHARMACEUTICAL CLASSES
1st wave: small molecules
→ Chemically synthesized and can easily enter cells to interact with specific
biological targets
→ Ex. statins (= cholesterol lowering)
→ Screen large numbers of compounds
→ Small molecule drugs are typically discovered through large-scale
screening of chemical libraries
→ Off-target effects/toxicity
→ A major challenge with small molecules is their potential to bind to
unintended targets, leading to side effects or toxicity
2nd wave: biologicals (= monoclonal antibodies)
→ Drugs derived from organisms
→ Designed by target specific action to the target
→ Fewer off-target effects
→ NO trial & error
→ Biggest advantage: frequency is much lower, you don’t need to take the drug that
often, so therapy compliance is much better
→ Ex. PCK9-inhibitors
3rd wave: genetic medicines
→ ATMP = Advanced Therapy Medicinal Product
→ Treats or modulates underlying cause
1
, → No off target effects
→ Often for rare diseases or genetic causes
→ mRNA based vaccines induce the endogenous production of non-self-proteins by
administering “synthetic” mRNA…
Endogenous expression of a “viral” antigen to which an immune response is
induced
→ So not only used for the inhibition of proteins, but also for the induction
→ Ex. siRNA
THE DRUG LIFECYCLE
Drug discovery:
Target selection
Target validation
Search for & selection of an NME
THREE LIFE PERIODS
1) Early development
→ Testing of the compound
→ Costs money investment needed to
get a drug on the market
2) Middle phase
→ Sales of the compound
→ Income = return of investment (ROI)
→ Hopefully bigger than spent
money in early development
3) Late phase
→ No more market exclusivity
→ After 20 years (patent expires)
→ Declined sales due to copies of the drug coming to the market
DRUG DEVELOPMENT
Exploratory phase = early development = non-clinical research, phase I & phase II
trials
→ Looking for the potential of the drug
→ Proving that the drug does what it is supposed to do & checking if it is safe
Confirmatory phase = late development = phase III & phase IV trials
→ Confirming what was found in early development
Pre-clinical or non-clinical development:
Non-clinical ADME
Toxicology & safety testing
Clinical development:
Phase I = exploring the safety of the drug in healthy people
Phase II = exploring the efficacy in a small group of patients
Phase III = confirming safety & efficacy in a large group of patients
2
,3
, First-in-human (FIH) test = trial for the first time in humans
→ Approval from authority needed
→ Clinical Trial Application (CTA) in Europe
→ Request admitted in Clinical Trial Information System (CTIS)
→ All clinical trials need to be submitted through 1 central directive
→ Clinical trial Regulation (CTR)
Post-approval phase = approval for marketing
→ Common Technical Document (CTD) = summary of all the risk found in the
clinical trials
→ Through a Marketing Authorization (MA) in Europe
→ Through a New Drug Application (NDA) in US
→ Reimbursement & commercialization need to be established
→ Through pharmacovigilance, post-marketing surveillance & society
Guidelines:
Quality standards & guidelines during early phase
o Good Laboratory Practice (GLP)
o Good Clinical Practice (GCP)
o Good Manufacturing Practice (GMP)
o Good Documentation Practice (GDP)
Ethical standards during clinical trials
o Nuremberg code
o Declaration of Helsinki
Regulations during post-approval phase
o CTR
o Medical device regulation (MDR)
o In vitro diagnostic regulation (IVDR)
o Belgian law on experiments
4
1. INTRODUCTION
DEFINITION
Medical discipline = speciality for medical doctors
→ includes discovery, development, evaluation registration, monitoring and medical
aspects of marketing of medicines for the benefit of patients and the health of the
community.
Pharmaceutical medicine is responsible for ensuring and maintaining standards in the
discipline and curriculum for higher medical training to equip specialists with the
comprehensive skills and competence increasingly demanded by the industry for the
public good
AUTHORIZATION & ADMINISTRATION OF DRUGS
EMA = European medicines agency
→ authorization for new medicines
In the last decade, the total number of drug approvals has generally increased, with some
peak years
→ most approvals are new molecular entities (NMEs)
PHARMACEUTICAL CLASSES
1st wave: small molecules
→ Chemically synthesized and can easily enter cells to interact with specific
biological targets
→ Ex. statins (= cholesterol lowering)
→ Screen large numbers of compounds
→ Small molecule drugs are typically discovered through large-scale
screening of chemical libraries
→ Off-target effects/toxicity
→ A major challenge with small molecules is their potential to bind to
unintended targets, leading to side effects or toxicity
2nd wave: biologicals (= monoclonal antibodies)
→ Drugs derived from organisms
→ Designed by target specific action to the target
→ Fewer off-target effects
→ NO trial & error
→ Biggest advantage: frequency is much lower, you don’t need to take the drug that
often, so therapy compliance is much better
→ Ex. PCK9-inhibitors
3rd wave: genetic medicines
→ ATMP = Advanced Therapy Medicinal Product
→ Treats or modulates underlying cause
1
, → No off target effects
→ Often for rare diseases or genetic causes
→ mRNA based vaccines induce the endogenous production of non-self-proteins by
administering “synthetic” mRNA…
Endogenous expression of a “viral” antigen to which an immune response is
induced
→ So not only used for the inhibition of proteins, but also for the induction
→ Ex. siRNA
THE DRUG LIFECYCLE
Drug discovery:
Target selection
Target validation
Search for & selection of an NME
THREE LIFE PERIODS
1) Early development
→ Testing of the compound
→ Costs money investment needed to
get a drug on the market
2) Middle phase
→ Sales of the compound
→ Income = return of investment (ROI)
→ Hopefully bigger than spent
money in early development
3) Late phase
→ No more market exclusivity
→ After 20 years (patent expires)
→ Declined sales due to copies of the drug coming to the market
DRUG DEVELOPMENT
Exploratory phase = early development = non-clinical research, phase I & phase II
trials
→ Looking for the potential of the drug
→ Proving that the drug does what it is supposed to do & checking if it is safe
Confirmatory phase = late development = phase III & phase IV trials
→ Confirming what was found in early development
Pre-clinical or non-clinical development:
Non-clinical ADME
Toxicology & safety testing
Clinical development:
Phase I = exploring the safety of the drug in healthy people
Phase II = exploring the efficacy in a small group of patients
Phase III = confirming safety & efficacy in a large group of patients
2
,3
, First-in-human (FIH) test = trial for the first time in humans
→ Approval from authority needed
→ Clinical Trial Application (CTA) in Europe
→ Request admitted in Clinical Trial Information System (CTIS)
→ All clinical trials need to be submitted through 1 central directive
→ Clinical trial Regulation (CTR)
Post-approval phase = approval for marketing
→ Common Technical Document (CTD) = summary of all the risk found in the
clinical trials
→ Through a Marketing Authorization (MA) in Europe
→ Through a New Drug Application (NDA) in US
→ Reimbursement & commercialization need to be established
→ Through pharmacovigilance, post-marketing surveillance & society
Guidelines:
Quality standards & guidelines during early phase
o Good Laboratory Practice (GLP)
o Good Clinical Practice (GCP)
o Good Manufacturing Practice (GMP)
o Good Documentation Practice (GDP)
Ethical standards during clinical trials
o Nuremberg code
o Declaration of Helsinki
Regulations during post-approval phase
o CTR
o Medical device regulation (MDR)
o In vitro diagnostic regulation (IVDR)
o Belgian law on experiments
4
