Biopharmaceuticals Flashcards
1
Q
Biopharmaceuticals
A
- Medical drugs or diagnostics produced using a biological process or biotechnology
- Often called “large molecules”
- Include proteins, peptides, DNA/RNA, and antibodies
2
Q
First Modern Product
A
- Genentech’s Humulin: human insulin made from recombinant DNA launched in 1982
3
Q
First Recombinant Vaccine
A
- Hep B was launched in 1986
- Produced from yeast
4
Q
Initial Protein Drugs
A
- Derived from human or animal blood or tissues (anti-venoms from snakes, insulin from animal pancreases)
- These methods didn’t allow for large scale production so recombinant methods developed
5
Q
Recombinant Methods
A
- Specific for each protein produced but similar general pathway:
1) isolate the gene responsible for protein synthesis
2) insert gene into DNA from yeast or bacteria cell
3) grow yeast or bacteria with the protein being expressed/grown by the yeast or bacteria
4) isolate the protein from the cells
6
Q
Delivery/Use of DNA/RNA is Difficult in Practice
A
- Replace a mutated gene with a healthy copy
- Inactivating a mutated gene
- Introducing a new gene into the body
7
Q
Delivery/insertion of DNA/RNA is key
A
- Viral vectors, bacterial vectors, ex vivo delivery, LPN, etc.
- Focus is to get the material where it is needed and enable insertion
8
Q
Current Antibodies
A
- Monoclonal antibody used to treat multiple cancers (i.e. lung, bladder, cervical, melanoma, etc.)
- Requires biomarker screening to confirm genetic make up of tumor
- Cost: $150,000/year +
9
Q
Biopharmaceutical Formulation
A
- Formulation is much more limited than small molecules
- Biopharmaceuticals can undergo both chemical degradation and physical degradation
- Both must be considered in formulation
10
Q
Physical Degradation
A
- De-naturing
- Fragmenting
- Aggregating
- Absorption to surfaces
11
Q
Formulation Techniques (5)
A
1) pH control
2) Temperature control
3) Adsorption/Aggregation
4) Mixing
5) Solubility increase
12
Q
1) pH Control
A
- Formulate at or near physiological pH
- Often require buffer as protein purification typically uses a counter ion that changes pH of final formulation
13
Q
2) Temperature Control
A
- Specific for each biopharmaceutical
- High temperature can de-nature
- Low temperature can inactivate or require heat shock prior to use
14
Q
3) Adsorption/Aggregation
A
- Biopharmaceuticals are often ‘sticky’ and require surfactant at a low concentration to minimize adsorption to containers or container
- Surfactants also decrease the incidence of aggregation
15
Q
4) Mixing
A
- Limited to techniques that can be used
- –stir bar/mild agitation works well
- –sonication, heat, and intense agitation often de-nature or fragment biopharmaceuticals
16
Q
5) Solubility Increase
A
- Often not an issue as most biopharmaceuticals are soluble in aqueous medias
- Limited number of excipient that can be used
- –cosolvents often de-nature
- –surfactants work well at low concentrations
- –complexing agents usually don’t result in sufficient increase in solubility w/o significant concentrations of complexing agent
17
Q
Biopharmaceutical Delivery
A
- Due to gastric pH and gastric enzyme’s oral delivery is not possible
- Primarily given as an injectable (subQ), nasally, oral inhalation or topically
18
Q
Inhalation Biopharmaceuticals
A
- Inhalation delivery of large molecules has shown promise
- Cyclosporine & Insulin
- Inhalation delivery of biopharmaceuticals has shown similar plasma concentration profiles as injectable drug delivery
19
Q
Inhalation Insulin
A
- Inhalation formulation of insulin mitigated many of the formulation issues above including: pH, ionic strength, mixing, solubility
- Allowed formulation to focus on temperature stability and inhalation delivery
