Pharmaceutical Medicine
Jan de Hoon
Master Biomedical Sciences KUL
By Karel Noppe
Table of Contents
1 Introduction
2 Drug design and discovery: part 1
3 Drug design and discovery: part 2
4 Pharmaceutical development
5 Clinical drug development: part 1
6 Clinical drug development: part 2
7 Clinical drug development: part 3
8 Clinical drug development: part 4
9 Clinical drug development: part 5
10 Special populations: part 1
11 Special populations: part 2
12 PBK modelling
13 Guidelines & regulations
14 Model-informed drug development
15 Small molecules & biologicals
16 Vaccine development
17 Pharmacovigilance
18 Health systems
19 Pricing & reimbursement
20 MA CTD
21 Drugs and society: part 1
22 Drugs and society: part 2
23 The medical department
24 Closing remarks
,Chapter 1: Introduction to
Pharmaceutical Medicine
Prof. Jan de Hoon | KU Leuven / University Hospitals Leuven | 2025–2026
What is Pharmaceutical Medicine?
Definition — Pharmaceutical Medicine
Pharmaceutical Medicine: the medical scientific discipline concerned with the
discovery, development, evaluation, registration, monitoring, and medical aspects
of marketing of medicines for the benefit of patients and public health.
• Aim of the discipline: providing a competent workforce to enable faster access to
better medicines for patients worldwide (ECPM/Front Pharmacol 2020; 11:282).
• Sits at the intersection of clinical pharmacology and pharmaceutical medicine;
involves medicine, pharmacy, regulation, and industry.
• Core activities: NCE/NME/NBE discovery; preclinical evaluation; clinical evaluation;
regulatory submission; marketing; post-marketing surveillance.
◦ NCE: New Chemical Entity; NME: New Molecular Entity; NBE: New Biological
Entity.
• Fundamentally interdisciplinary: requires collaboration across medical, pharmacy,
regulatory, and industry teams.
Why Pharmaceutical Medicine Matters — Market Context
• Top product forecasts 2025 (Nature Reviews Drug Discovery, January 2025):
dominated by biologicals — mAbs and peptides.
◦ Key therapeutic areas: oncology (e.g. Keytruda, anti-PD1 mAb, ~$31B),
inflammation/immunology (Dupixent, Skyrizi), obesity/metabolic (Ozempic,
Mounjaro, Wegovy, Zepbound).
◦ Illustrates the shift from small molecules to large-molecule biologicals as
dominant class.
• 2024 EMA approvals: included PRIME medicines (priority review), orphan
medicines, ATMPs, and biosimilars.
• 2024 FDA approvals (Nature Reviews Drug Discovery): classified as NMEs and BLAs
across multiple therapeutic areas including oncology, CNS, and rare diseases.
Three Waves of Pharmaceutical Innovation
• 1st wave — Small molecules (~1900s): classical symptomatic drugs;
enzyme/receptor inhibitors; small, synthetically produced; oral bioavailability; Lipinski
Rule of Five applies.
• 2nd wave — Monoclonal antibodies (mAbs) (~1980s onwards): large biologicals;
highly specific; parenteral administration; violate Rule of Five.
, ◦ Example: PCSK9-targeting mAbs (alirocumab, evolocumab) for LDL-cholesterol
lowering — block PCSK9, allowing more LDL-R recycling in hepatocytes →
increased LDL uptake (NEJM 2020; 383:711).
• 3rd wave — siRNA / mRNA / ATMPs (~2000s–present): nucleic acid-based therapies
and advanced therapy medicinal products.
◦ siRNA example: inclisiran — silences PCSK9 gene via RNAi, twice-yearly
injection for LDL lowering (NEJM 2017; 376:4 and NEJM 2020; 382:1507).
◦ mRNA example: SARS-CoV-2 mRNA vaccines (Comirnaty) — induce
endogenous production of non-self antigen (spike protein) to elicit immunity;
landmark 3rd-wave application.
• The waves are on the move: ATMPs (gene therapies, cell therapies, tissue-
engineered products) are the emerging frontier.
Pharmaceutical Classes of Drugs
• Small molecules: low MW (<500 Da); synthetically manufactured; oral route possible;
metabolised by CYPs; covered by Rule of Five.
• Biologicals: large, complex molecules derived from biological systems; includes
mAbs, fusion proteins, enzymes, hormones.
• Monoclonal antibodies (mAbs): IgG-based; target-specific; mechanisms include
ligand blockade, receptor blockade, ADCC, CDC; naming suffix tells origin (-omab
murine → -ximab chimeric → -zumab humanised → -umab fully human).
• Vaccines: prophylactic/therapeutic immune stimulation; traditional (live-attenuated,
inactivated) and next-gen (mRNA, viral vector, subunit).
• Peptides: intermediate between small molecules and biologicals; examples: GLP-1
agonists (semaglutide/Ozempic).
• Nucleic acid-based therapies: siRNA, antisense oligonucleotides (ASOs), mRNA
therapeutics; gene silencing or replacement.
• ATMPs — Advanced Therapy Medicinal Products: gene therapy products
(modifying patient's genes), somatic cell therapy products, and tissue-engineered
products; regulated under specific EMA framework.
The Full Drug Life Cycle
• Overview of sequential stages:
◦ 1. Discovery: target identification/validation; hit finding; lead optimisation.
◦ 2. Preclinical / non-clinical development: in vitro and in vivo safety (GLP
studies); pharmaceutical development (formulation); ADME/PK profiling.
◦ 3. Clinical development: Phase I (FIH, safety, PK) → Phase II (efficacy, dose-
finding, PoC) → Phase III (confirmatory, large RCT).
◦ 4. Regulatory submission & approval: CTD (Common Technical Document) →
MAA (EU/EMA) or NDA/BLA (US/FDA) → Marketing Authorisation.
◦ 5. Post-approval / Phase IV: pharmacovigilance; PSUR; signal detection; RMP;
reimbursement; commercialisation.
◦ 6. Generic / biosimilar entry: after patent expiry; generics for small molecules,
biosimilars for biologicals.
, • IND / CTA: required before clinical trials can start in the US (IND = Investigational New
Drug, FDA) and EU (CTA = Clinical Trial Application, national/CTIS).
• The life cycle is also a pharmaceutical reward system: financial return is structured
around IP exclusivity periods and policy incentives — a key theme throughout the
course.
Good Practice Standards (GxP)
• GLP — Good Laboratory Practice: standards for non-clinical (preclinical) safety
studies; ensures data quality and integrity; mandatory for regulatory toxicology studies.
• GMP — Good Manufacturing Practice: standards for manufacturing pharmaceutical
products; ensures consistent quality, purity, and safety of drug substance and drug
product.
• GCP — Good Clinical Practice: international ethical and scientific quality standard for
designing, conducting, recording, and reporting clinical trials (ICH-GCP E6).
• GDP — Good Documentation Practice: standards ensuring accuracy, completeness,
and traceability of records throughout drug development and distribution.
• These standards apply at different stages of the life cycle: GLP during preclinical, GMP
throughout manufacturing, GCP during clinical trials.
Ethical Foundations of Clinical Research
• Nuremberg Code (1947): arose after WWII Nazi medical experiments; established 10
principles including voluntary informed consent, avoidance of unnecessary harm,
freedom to withdraw.
• Declaration of Helsinki (WMA, first 1964; current version 2024): physician-led
ethical principles for medical research involving humans; expanded to vulnerable
populations, post-trial access, registry obligations.
◦ Controversial additions around 2000: mandatory placebo vs. best available
treatment; post-trial obligations; continued access after study.
• ICH-GCP (ICH E6): harmonised international standard operationalising Helsinki
principles; mandatory framework for clinical trials globally.
• Together these form the ethical scaffold underpinning all clinical research: informed
consent, independent ethics review, benefit–risk balance, and protection of research
subjects.
Key Regulatory Terminology
• EMA: European Medicines Agency (Amsterdam); centralised EU regulatory authority;
responsible for scientific evaluation, supervision, and safety monitoring of medicines in
EU.
• FDA: Food and Drug Administration (USA); equivalent US authority; issues INDs,
NDAs, BLAs.
• FAMHP / FAGG: Federal Agency for Medicines and Health Products (Belgium);
national competent authority; processes national MAs, monitors pharmacovigilance
locally.
• CTA: Clinical Trial Application (EU) — submitted before clinical trials begin; now via
CTIS (Clinical Trials Information System) portal for pan-EU single submission.
Jan de Hoon
Master Biomedical Sciences KUL
By Karel Noppe
Table of Contents
1 Introduction
2 Drug design and discovery: part 1
3 Drug design and discovery: part 2
4 Pharmaceutical development
5 Clinical drug development: part 1
6 Clinical drug development: part 2
7 Clinical drug development: part 3
8 Clinical drug development: part 4
9 Clinical drug development: part 5
10 Special populations: part 1
11 Special populations: part 2
12 PBK modelling
13 Guidelines & regulations
14 Model-informed drug development
15 Small molecules & biologicals
16 Vaccine development
17 Pharmacovigilance
18 Health systems
19 Pricing & reimbursement
20 MA CTD
21 Drugs and society: part 1
22 Drugs and society: part 2
23 The medical department
24 Closing remarks
,Chapter 1: Introduction to
Pharmaceutical Medicine
Prof. Jan de Hoon | KU Leuven / University Hospitals Leuven | 2025–2026
What is Pharmaceutical Medicine?
Definition — Pharmaceutical Medicine
Pharmaceutical Medicine: the medical scientific discipline concerned with the
discovery, development, evaluation, registration, monitoring, and medical aspects
of marketing of medicines for the benefit of patients and public health.
• Aim of the discipline: providing a competent workforce to enable faster access to
better medicines for patients worldwide (ECPM/Front Pharmacol 2020; 11:282).
• Sits at the intersection of clinical pharmacology and pharmaceutical medicine;
involves medicine, pharmacy, regulation, and industry.
• Core activities: NCE/NME/NBE discovery; preclinical evaluation; clinical evaluation;
regulatory submission; marketing; post-marketing surveillance.
◦ NCE: New Chemical Entity; NME: New Molecular Entity; NBE: New Biological
Entity.
• Fundamentally interdisciplinary: requires collaboration across medical, pharmacy,
regulatory, and industry teams.
Why Pharmaceutical Medicine Matters — Market Context
• Top product forecasts 2025 (Nature Reviews Drug Discovery, January 2025):
dominated by biologicals — mAbs and peptides.
◦ Key therapeutic areas: oncology (e.g. Keytruda, anti-PD1 mAb, ~$31B),
inflammation/immunology (Dupixent, Skyrizi), obesity/metabolic (Ozempic,
Mounjaro, Wegovy, Zepbound).
◦ Illustrates the shift from small molecules to large-molecule biologicals as
dominant class.
• 2024 EMA approvals: included PRIME medicines (priority review), orphan
medicines, ATMPs, and biosimilars.
• 2024 FDA approvals (Nature Reviews Drug Discovery): classified as NMEs and BLAs
across multiple therapeutic areas including oncology, CNS, and rare diseases.
Three Waves of Pharmaceutical Innovation
• 1st wave — Small molecules (~1900s): classical symptomatic drugs;
enzyme/receptor inhibitors; small, synthetically produced; oral bioavailability; Lipinski
Rule of Five applies.
• 2nd wave — Monoclonal antibodies (mAbs) (~1980s onwards): large biologicals;
highly specific; parenteral administration; violate Rule of Five.
, ◦ Example: PCSK9-targeting mAbs (alirocumab, evolocumab) for LDL-cholesterol
lowering — block PCSK9, allowing more LDL-R recycling in hepatocytes →
increased LDL uptake (NEJM 2020; 383:711).
• 3rd wave — siRNA / mRNA / ATMPs (~2000s–present): nucleic acid-based therapies
and advanced therapy medicinal products.
◦ siRNA example: inclisiran — silences PCSK9 gene via RNAi, twice-yearly
injection for LDL lowering (NEJM 2017; 376:4 and NEJM 2020; 382:1507).
◦ mRNA example: SARS-CoV-2 mRNA vaccines (Comirnaty) — induce
endogenous production of non-self antigen (spike protein) to elicit immunity;
landmark 3rd-wave application.
• The waves are on the move: ATMPs (gene therapies, cell therapies, tissue-
engineered products) are the emerging frontier.
Pharmaceutical Classes of Drugs
• Small molecules: low MW (<500 Da); synthetically manufactured; oral route possible;
metabolised by CYPs; covered by Rule of Five.
• Biologicals: large, complex molecules derived from biological systems; includes
mAbs, fusion proteins, enzymes, hormones.
• Monoclonal antibodies (mAbs): IgG-based; target-specific; mechanisms include
ligand blockade, receptor blockade, ADCC, CDC; naming suffix tells origin (-omab
murine → -ximab chimeric → -zumab humanised → -umab fully human).
• Vaccines: prophylactic/therapeutic immune stimulation; traditional (live-attenuated,
inactivated) and next-gen (mRNA, viral vector, subunit).
• Peptides: intermediate between small molecules and biologicals; examples: GLP-1
agonists (semaglutide/Ozempic).
• Nucleic acid-based therapies: siRNA, antisense oligonucleotides (ASOs), mRNA
therapeutics; gene silencing or replacement.
• ATMPs — Advanced Therapy Medicinal Products: gene therapy products
(modifying patient's genes), somatic cell therapy products, and tissue-engineered
products; regulated under specific EMA framework.
The Full Drug Life Cycle
• Overview of sequential stages:
◦ 1. Discovery: target identification/validation; hit finding; lead optimisation.
◦ 2. Preclinical / non-clinical development: in vitro and in vivo safety (GLP
studies); pharmaceutical development (formulation); ADME/PK profiling.
◦ 3. Clinical development: Phase I (FIH, safety, PK) → Phase II (efficacy, dose-
finding, PoC) → Phase III (confirmatory, large RCT).
◦ 4. Regulatory submission & approval: CTD (Common Technical Document) →
MAA (EU/EMA) or NDA/BLA (US/FDA) → Marketing Authorisation.
◦ 5. Post-approval / Phase IV: pharmacovigilance; PSUR; signal detection; RMP;
reimbursement; commercialisation.
◦ 6. Generic / biosimilar entry: after patent expiry; generics for small molecules,
biosimilars for biologicals.
, • IND / CTA: required before clinical trials can start in the US (IND = Investigational New
Drug, FDA) and EU (CTA = Clinical Trial Application, national/CTIS).
• The life cycle is also a pharmaceutical reward system: financial return is structured
around IP exclusivity periods and policy incentives — a key theme throughout the
course.
Good Practice Standards (GxP)
• GLP — Good Laboratory Practice: standards for non-clinical (preclinical) safety
studies; ensures data quality and integrity; mandatory for regulatory toxicology studies.
• GMP — Good Manufacturing Practice: standards for manufacturing pharmaceutical
products; ensures consistent quality, purity, and safety of drug substance and drug
product.
• GCP — Good Clinical Practice: international ethical and scientific quality standard for
designing, conducting, recording, and reporting clinical trials (ICH-GCP E6).
• GDP — Good Documentation Practice: standards ensuring accuracy, completeness,
and traceability of records throughout drug development and distribution.
• These standards apply at different stages of the life cycle: GLP during preclinical, GMP
throughout manufacturing, GCP during clinical trials.
Ethical Foundations of Clinical Research
• Nuremberg Code (1947): arose after WWII Nazi medical experiments; established 10
principles including voluntary informed consent, avoidance of unnecessary harm,
freedom to withdraw.
• Declaration of Helsinki (WMA, first 1964; current version 2024): physician-led
ethical principles for medical research involving humans; expanded to vulnerable
populations, post-trial access, registry obligations.
◦ Controversial additions around 2000: mandatory placebo vs. best available
treatment; post-trial obligations; continued access after study.
• ICH-GCP (ICH E6): harmonised international standard operationalising Helsinki
principles; mandatory framework for clinical trials globally.
• Together these form the ethical scaffold underpinning all clinical research: informed
consent, independent ethics review, benefit–risk balance, and protection of research
subjects.
Key Regulatory Terminology
• EMA: European Medicines Agency (Amsterdam); centralised EU regulatory authority;
responsible for scientific evaluation, supervision, and safety monitoring of medicines in
EU.
• FDA: Food and Drug Administration (USA); equivalent US authority; issues INDs,
NDAs, BLAs.
• FAMHP / FAGG: Federal Agency for Medicines and Health Products (Belgium);
national competent authority; processes national MAs, monitors pharmacovigilance
locally.
• CTA: Clinical Trial Application (EU) — submitted before clinical trials begin; now via
CTIS (Clinical Trials Information System) portal for pan-EU single submission.
