Biopharmaceuticals: prof. Delputte
WHAT ARE BIOPHARMACEUTICALS?
For example EPO, insulin, vaccines, mAb,…
1. Protein-like structures
2. Oligonucleotides
3. Sugars / glycans
a. Usually not used: too complex & usually low
affinity to targets: side effects
4. Cell-typing
a. Isolate cells from patients, treat them and inject them again
Biopharmaceuticals are VALUABLE. You can have novel innovative therapies for significant unmet
medical needs. It is a radically new approach. 1/3 – ½ of all drugs in development are
biopharmaceuticals.
- NME = new molecular entity = when a small molecule goes into development
- NBE = new biological entity
Advantages !!!
Inherently highly specific for the target
Minimum risk for non-mechanism based toxicity and safety
Capable of increasing growth factors, hormones, enzymes…
Can modulate protein/protein interactions that cannot be targeted by small molecules
Applicability in multiple therapeutic areas and for multiple targets
Value
o Larger profits for companies
o Therapeutic value
Definition
Small molecules are usually taken orally, while biopharmaceuticals are mostly administered IV.
The term biopharmeuticals is widely used, but is hardly ever defined by its users, definitions of
biopharmaceuticals in common use vary greatly.
- Pharmaceutical: involves chemical (non-biological) medicinal products manufactured using
chemical sources and processes.
- Biopharmaceutical: involves inherently biological products with manufacture involving
biological sources and processes
= Everything that living organisms can make: proteins, nucleic acids, glycans, viruses, bacteria,
vaccines, cell-based therapies…
Problem of antisera / antibodies = we make antibodies against the antibodies of the horse.
Antivenom usually only works once. Also biologicals are unstable and difficult to store.
, Insulin was already discovered in 1921. People would extract bovine insulin and inject it in humans.
This had a lot of problems in efficacy and purity. Next with chromatography it was possible to purify
the insulin more. The major breakthrough however was done by Genentech: they manipulating
bacteria and produced insulin in bacteria with the same AA as in humans. Insulin thus used to be a
natural product and in the end became a biotechnological product.
NATURAL PRODUCT VS BIOTECHNOLOGICAL PRODUCT
The development of human growth hormone, insulin and RBC stimulating agents occurred decades
ago. These could be easily produced in bacteria or other simple organisms.
- Natural products are difficult to make in large quantities: you can only extract as much insulin
as you have in the pancreas. Also very expensive and difficult to purify = old biologicals
o Immune responses against the old biopharmaceuticals
o Batch to batch variability & lower purity
o Safety
o Low quantities available
- Biotech products allows to make much more pure products. It is easier to purify and it is
cheaper. Made by recombinant technology = new biologicals
Updated definition: everything that is made from a living source (cell) and is the result of
biotechnological intervention. But this is not complete yet because what about antisense
oligonucleotides, scaffolds, RNA interference, amino acids…
SYNTHETIC BIOLOGY
- Biopharmaceutical because it mimics biological molecules
- Drugs because they are almost always synthetic
Insulin is made recombinantly but it can also be made fully synthetically. Chemical synthesis is quite
expensive though, and you might consider it not to be a biopharmaceutical anymore. DNA used to be
made in bacteria but it can be made now synthetically. You can then also not consider it being a
biopharmaceutical anymore.
It is not about what it is but how it has been made!
Updated definition: Large complex molecules that are made from a living source (cell) and are the
result of (biotechnological) intervention/manipulation.
DIFFERENCES BIOPHARMACEUTICALS & PHARMACEUTICALS
Complexity & variability make it difficult to make a generic biopharmaceutical. For regulatory filing
you have to show the molecule and structure is the same each time. BUT each time you use AB they
will probably have the same AA sequence (not always), but you will have some differences:
aggregates, different PTM, disulphide bridges, glycans… You can’t undoubtly describe the product.
You just need to show it has the same functionality. (Also difficult for intellectual property).
WHAT ARE BIOPHARMACEUTICALS?
For example EPO, insulin, vaccines, mAb,…
1. Protein-like structures
2. Oligonucleotides
3. Sugars / glycans
a. Usually not used: too complex & usually low
affinity to targets: side effects
4. Cell-typing
a. Isolate cells from patients, treat them and inject them again
Biopharmaceuticals are VALUABLE. You can have novel innovative therapies for significant unmet
medical needs. It is a radically new approach. 1/3 – ½ of all drugs in development are
biopharmaceuticals.
- NME = new molecular entity = when a small molecule goes into development
- NBE = new biological entity
Advantages !!!
Inherently highly specific for the target
Minimum risk for non-mechanism based toxicity and safety
Capable of increasing growth factors, hormones, enzymes…
Can modulate protein/protein interactions that cannot be targeted by small molecules
Applicability in multiple therapeutic areas and for multiple targets
Value
o Larger profits for companies
o Therapeutic value
Definition
Small molecules are usually taken orally, while biopharmaceuticals are mostly administered IV.
The term biopharmeuticals is widely used, but is hardly ever defined by its users, definitions of
biopharmaceuticals in common use vary greatly.
- Pharmaceutical: involves chemical (non-biological) medicinal products manufactured using
chemical sources and processes.
- Biopharmaceutical: involves inherently biological products with manufacture involving
biological sources and processes
= Everything that living organisms can make: proteins, nucleic acids, glycans, viruses, bacteria,
vaccines, cell-based therapies…
Problem of antisera / antibodies = we make antibodies against the antibodies of the horse.
Antivenom usually only works once. Also biologicals are unstable and difficult to store.
, Insulin was already discovered in 1921. People would extract bovine insulin and inject it in humans.
This had a lot of problems in efficacy and purity. Next with chromatography it was possible to purify
the insulin more. The major breakthrough however was done by Genentech: they manipulating
bacteria and produced insulin in bacteria with the same AA as in humans. Insulin thus used to be a
natural product and in the end became a biotechnological product.
NATURAL PRODUCT VS BIOTECHNOLOGICAL PRODUCT
The development of human growth hormone, insulin and RBC stimulating agents occurred decades
ago. These could be easily produced in bacteria or other simple organisms.
- Natural products are difficult to make in large quantities: you can only extract as much insulin
as you have in the pancreas. Also very expensive and difficult to purify = old biologicals
o Immune responses against the old biopharmaceuticals
o Batch to batch variability & lower purity
o Safety
o Low quantities available
- Biotech products allows to make much more pure products. It is easier to purify and it is
cheaper. Made by recombinant technology = new biologicals
Updated definition: everything that is made from a living source (cell) and is the result of
biotechnological intervention. But this is not complete yet because what about antisense
oligonucleotides, scaffolds, RNA interference, amino acids…
SYNTHETIC BIOLOGY
- Biopharmaceutical because it mimics biological molecules
- Drugs because they are almost always synthetic
Insulin is made recombinantly but it can also be made fully synthetically. Chemical synthesis is quite
expensive though, and you might consider it not to be a biopharmaceutical anymore. DNA used to be
made in bacteria but it can be made now synthetically. You can then also not consider it being a
biopharmaceutical anymore.
It is not about what it is but how it has been made!
Updated definition: Large complex molecules that are made from a living source (cell) and are the
result of (biotechnological) intervention/manipulation.
DIFFERENCES BIOPHARMACEUTICALS & PHARMACEUTICALS
Complexity & variability make it difficult to make a generic biopharmaceutical. For regulatory filing
you have to show the molecule and structure is the same each time. BUT each time you use AB they
will probably have the same AA sequence (not always), but you will have some differences:
aggregates, different PTM, disulphide bridges, glycans… You can’t undoubtly describe the product.
You just need to show it has the same functionality. (Also difficult for intellectual property).
