1st Master Biomedical Sciences
Pharmaceutical Medicine
Overview of open questions 2025
Content
Introduction............................................................................................................................................................ 1
Drug design and discovery .................................................................................................................................... 1
Pharmaceutical development ................................................................................................................................. 2
Clinical drug development ..................................................................................................................................... 6
Special populations .............................................................................................................................................. 14
Pharmacometrics.................................................................................................................................................. 16
Guidelines and regulations in clinical research .................................................................................................... 16
Small molecules and biologicals .......................................................................................................................... 18
Pharmacovigilance ............................................................................................................................................... 19
Vaccine development ........................................................................................................................................... 20
Regulations concerning MA ................................................................................................................................ 21
Reimbursements .................................................................................................................................................. 22
Medical department ............................................................................................................................................. 23
Closing remarks ................................................................................................................................................... 23
Drugs and society ................................................................................................................................................ 24
One (1) of these questions is part of the exam:
Introduction
1. Give an overview of the different pharmaceutical classes of drugs which are available.
a. Small molecules
i. They have a defined chemical synthesis and identical copies can be made
ii. They are relatively simple and well-defined molecules and relatively stable
iii. E.g. statins
b. Biologicals
i. Produced through biotechnology in a living system where the active substance is derived
from
ii. Designed for target therefore more specific and less off-target effects but risk of antidrug
antibodies
iii. They are relatively large and complex molecules
iv. E.g. PCSK9 inhibitors
c. Oligonucleotides
i. Genetic medicine that treats/modulate underlying cause and is used often for rare disease
and/or with genetic causes
ii. Include siRNA, gene therapy etc.
iii. E.g. ATMPs
Drug design and discovery
2. Discuss the strengths and limitations of target-based versus phenotypic drug discovery. Give examples
1ste Master Biomedical Sciences / Pharmaceutical Medicine / questions / version 2025 1
, PDD
Empirical, “holistic” method based on observable characteristics (readouts) of an organism (cell, animal)
• Positive
o Target-agnostic, “target unbiased” approach: knowledge of pathomechanistic details
unnecessary
o Increased chance on first-in-class medication
o In vivo: indirectly ADME tested
o High predictive validity when chain of translatability is present
▪ Chain of translatability: A molecular-level association between the mechanisms that
drive the assay phenotype, the preclinical disease model and the human disease.
• Negative
o No knowledge of target: no way to optimise structure
o Often “low throughput” (in vivo)
• Example: antitumoral assay
o Mouse model: Mice treated with vehicle (control) and one with the compound of interest.
They are then injected with cancer cells. If the compound is well tolerated, the weight of the
animals stays relatively the same. When sacrificed, they weigh the tumour, and if it is lighter,
the compound works better.
TDD
Rational, “molecular” method based on knowledge of pathomechanism. It is used in fundamental biomedical
research→ published data → target.
• Positive
o “High throughput” possible
o MoAbs approach possible
o Rational method: intellectually attractive (evidence based)
• Negative
o Not always validation target
o Question whether it is relevant in the larger context
• Example: kinase assay
o In the enzyme kinase assay, they immobilise a certain polypeptide. Then, ATP and kinase of
interest are added. Phosphorylation occurs, which can be recognised by an antibody labelled
with a colour. No phosphorylation means less colour.
3. Discuss the strengths and limitations of the two different approaches to drug discovery. Give examples
See question 2
Pharmaceutical development
4. Provide an overview of the physicochemical and biopharmaceutical aspects which are being
investigated during the pre-formulation phase as part of the “pharmaceutical profiling” of an API.
Physicochemical characterisation of the API, also in combination with potential excipients
Biopharmaceutical properties (e.g. permeability characteristics)
1. Solubility and in vitro dissolution rate
1ste Master Biomedical Sciences / Pharmaceutical Medicine / questions / version 2025 2
, o Depending on the solubility, the dosage form should be chosen
▪ Solubility can be determined via e.g. FASSIF and FESSIF
▪ Solubility can be influenced by products that increase it e.g. cosolvents
▪ Analytical technique: UV spectroscopy etc.
o Oral availability is determined by solubility in the GI fluids
▪ Nernst-Brunner
• D = diffussion coefficient
• S = surface area
• h = diffusion layer thickness
• (Cs-Ct): concentration gradient, plays on the membrane of the
particle (takes place at the surface of the solvent particle)
2. Ionisation behaviour
o Base vs acidic compounds
o Determination of pKa (acid) and pKb
(base)
▪ S0= intrinsic solubility
▪ S= total solubility
o Ionisation form determines their lipophilic (non-ionized) or hydrophilic state
(ionized)
▪ pH influences the degree of ionisation (pH↑→ solubility↓)
o Possibility to consider salt formation→ lots of medications are salt formations
(improve solubility)
o If solvent is added, it changes polarity
3. Partition/distribution coefficient
o P=[D]l/[D]H2O
o Indication of lipophilicity and hydrophilicity
▪ > 1 lipophilic
o Indication of in vivo absorption (passive diffusion)
o N-octanol is most commonly used solvent
4. Solid state properties of API
o Crystalline (already stable)→ preferential state of matter
o Amorphous (glass)
▪ Higher solubility and dissolution rate
o Chemical stability of solid state or solution
5. Permeability
o API must be absorbed into the system to be active
o Parallel artificial membrane permeation assay (PAMPA)
▪ Donor and acceptor well with an artificial membrane, which is impregnated
with phospholipids+ cholesterol in dodecanol
• How much of the drug is migrating from donor to the acceptor
▪ Pros:
• Cheap
• Simple
• Fast
• High throughput
• No animals
• Different lipid compositions
1ste Master Biomedical Sciences / Pharmaceutical Medicine / questions / version 2025 3
Pharmaceutical Medicine
Overview of open questions 2025
Content
Introduction............................................................................................................................................................ 1
Drug design and discovery .................................................................................................................................... 1
Pharmaceutical development ................................................................................................................................. 2
Clinical drug development ..................................................................................................................................... 6
Special populations .............................................................................................................................................. 14
Pharmacometrics.................................................................................................................................................. 16
Guidelines and regulations in clinical research .................................................................................................... 16
Small molecules and biologicals .......................................................................................................................... 18
Pharmacovigilance ............................................................................................................................................... 19
Vaccine development ........................................................................................................................................... 20
Regulations concerning MA ................................................................................................................................ 21
Reimbursements .................................................................................................................................................. 22
Medical department ............................................................................................................................................. 23
Closing remarks ................................................................................................................................................... 23
Drugs and society ................................................................................................................................................ 24
One (1) of these questions is part of the exam:
Introduction
1. Give an overview of the different pharmaceutical classes of drugs which are available.
a. Small molecules
i. They have a defined chemical synthesis and identical copies can be made
ii. They are relatively simple and well-defined molecules and relatively stable
iii. E.g. statins
b. Biologicals
i. Produced through biotechnology in a living system where the active substance is derived
from
ii. Designed for target therefore more specific and less off-target effects but risk of antidrug
antibodies
iii. They are relatively large and complex molecules
iv. E.g. PCSK9 inhibitors
c. Oligonucleotides
i. Genetic medicine that treats/modulate underlying cause and is used often for rare disease
and/or with genetic causes
ii. Include siRNA, gene therapy etc.
iii. E.g. ATMPs
Drug design and discovery
2. Discuss the strengths and limitations of target-based versus phenotypic drug discovery. Give examples
1ste Master Biomedical Sciences / Pharmaceutical Medicine / questions / version 2025 1
, PDD
Empirical, “holistic” method based on observable characteristics (readouts) of an organism (cell, animal)
• Positive
o Target-agnostic, “target unbiased” approach: knowledge of pathomechanistic details
unnecessary
o Increased chance on first-in-class medication
o In vivo: indirectly ADME tested
o High predictive validity when chain of translatability is present
▪ Chain of translatability: A molecular-level association between the mechanisms that
drive the assay phenotype, the preclinical disease model and the human disease.
• Negative
o No knowledge of target: no way to optimise structure
o Often “low throughput” (in vivo)
• Example: antitumoral assay
o Mouse model: Mice treated with vehicle (control) and one with the compound of interest.
They are then injected with cancer cells. If the compound is well tolerated, the weight of the
animals stays relatively the same. When sacrificed, they weigh the tumour, and if it is lighter,
the compound works better.
TDD
Rational, “molecular” method based on knowledge of pathomechanism. It is used in fundamental biomedical
research→ published data → target.
• Positive
o “High throughput” possible
o MoAbs approach possible
o Rational method: intellectually attractive (evidence based)
• Negative
o Not always validation target
o Question whether it is relevant in the larger context
• Example: kinase assay
o In the enzyme kinase assay, they immobilise a certain polypeptide. Then, ATP and kinase of
interest are added. Phosphorylation occurs, which can be recognised by an antibody labelled
with a colour. No phosphorylation means less colour.
3. Discuss the strengths and limitations of the two different approaches to drug discovery. Give examples
See question 2
Pharmaceutical development
4. Provide an overview of the physicochemical and biopharmaceutical aspects which are being
investigated during the pre-formulation phase as part of the “pharmaceutical profiling” of an API.
Physicochemical characterisation of the API, also in combination with potential excipients
Biopharmaceutical properties (e.g. permeability characteristics)
1. Solubility and in vitro dissolution rate
1ste Master Biomedical Sciences / Pharmaceutical Medicine / questions / version 2025 2
, o Depending on the solubility, the dosage form should be chosen
▪ Solubility can be determined via e.g. FASSIF and FESSIF
▪ Solubility can be influenced by products that increase it e.g. cosolvents
▪ Analytical technique: UV spectroscopy etc.
o Oral availability is determined by solubility in the GI fluids
▪ Nernst-Brunner
• D = diffussion coefficient
• S = surface area
• h = diffusion layer thickness
• (Cs-Ct): concentration gradient, plays on the membrane of the
particle (takes place at the surface of the solvent particle)
2. Ionisation behaviour
o Base vs acidic compounds
o Determination of pKa (acid) and pKb
(base)
▪ S0= intrinsic solubility
▪ S= total solubility
o Ionisation form determines their lipophilic (non-ionized) or hydrophilic state
(ionized)
▪ pH influences the degree of ionisation (pH↑→ solubility↓)
o Possibility to consider salt formation→ lots of medications are salt formations
(improve solubility)
o If solvent is added, it changes polarity
3. Partition/distribution coefficient
o P=[D]l/[D]H2O
o Indication of lipophilicity and hydrophilicity
▪ > 1 lipophilic
o Indication of in vivo absorption (passive diffusion)
o N-octanol is most commonly used solvent
4. Solid state properties of API
o Crystalline (already stable)→ preferential state of matter
o Amorphous (glass)
▪ Higher solubility and dissolution rate
o Chemical stability of solid state or solution
5. Permeability
o API must be absorbed into the system to be active
o Parallel artificial membrane permeation assay (PAMPA)
▪ Donor and acceptor well with an artificial membrane, which is impregnated
with phospholipids+ cholesterol in dodecanol
• How much of the drug is migrating from donor to the acceptor
▪ Pros:
• Cheap
• Simple
• Fast
• High throughput
• No animals
• Different lipid compositions
1ste Master Biomedical Sciences / Pharmaceutical Medicine / questions / version 2025 3
