Protein Based drugs Flashcards
Protein Composition
What type of chain and what is it made up out of?
How many naturally occuring types?
What are 4 ways their chemical makeup varies?
What are the 4 protein structure types?
What are those made up of?
Examples of post-translational modifications and degradation of proteind in vivo
7 things
Protein Stability
Which state is more stable? Unfolded or Folded? Numerically how much more stable?
4 points pertaining to this?
- How many Hydrogen bonds?
- What about small proteins?
- What is only marginally stable?
- Unfolding?
Protein stability refers to?
Protein folding
Driving force based on what sequence?
4 points? Vs. What other point?
- Collapse?
- What interactions?
- What bonding?
- This list is not?
Vs.
- Protein and water? Entropy?
Protein Folding
We say that it cannot be a? What paradox?
What about the timescale of protein folding?
Therefore? 3 points
- What type of folding and what type of intermediates?
- What do solvent interactions do?
- What type of proteins in vivo
Introduction
Recombinant proteins made from different cell lines leading to? AS in what are the 3 types of organisms used for protein things
3 cell types used
Proteins are Sensitive what 4 things are they sensitive to? What makes them not work
Formulation Turning molecules into medicine 4 things
- What do you do for clinical admin?
- What do you need to figure out when the pt is taking it?
- How lng can it last?
- Friendly to who?
Monoclonal antibodies picture
What is the difference between Small Drugs and Large biologics in terms of how they are made up
Monoclonal antibody structure
2 portions?
Important physical characteristics 5
- How heavy?
- How many AAs?
- Domain?
- Sugar?
- Type of molecule?
Dynamic Behavior of Immunoglabulins
What region connects Immunoglubulin fragments? 2 parts of this?
What is between V and C domains?
2 types of motions
Sidechain?
Ven Diagram
Preformulation Characterization:
Determine Degradation Pathways and Physiochemical Stability Profile
4 parts
The end thing in the middle is?
Examples of Protein drug Heterogeneity?
3
Question is what makes the proteins vary non hemogenous
Protein Degradation pathways In Vitro
Chemical Pathways 8
Just know the differences between the two
Physical Pathways 4 and 4 subs in last one
Examples of Chemical Degradation Pathways
5 and examples within those
Examples of Chemical Degradations pathwzys
Protein?
Protein Met Oxidation
Protein Trp oxidation
Physical degradation pathways of protein therapeutics
5 things and these cause what 2 things?
What is the solution to the problem?
Protein Aggregation
Model of Multi state process of Non-Native Protein aggregation
What is the best and most effective form of the protein?
Because of this what do you want to prevent?
The goal is to keep the protein in as mich of the monomer form as possible or to have it readily be reversed back into the monomer so the drug can still be active
Protein Physical Stability and Aggregation
Two general categories:
Two roles
Role of conformational stability?
2 points
Role of Colloidal Stability 2 points?
What happens as a consequence of attractive intermolecular forces?
What influences proximity?
Stresses Affecting Protein Physical Stability two general categories
Role of environmental stresses?
Role of solution conditions?
Effect of environment stresses and solution conditions on: what 4 things?
Factors influencing Immunogenicity of Therapeutic Proteins
Picture of a bunch of stuff
What is formulation development for protein drugs?
- Drug at the appropriate?
- Excipients to ensure?
- Primary?
- For admin?
- What type of manufacturing process?
- Develop what methods?
- Define what conditions?
Goals for Formulation
The protein needs to be stable how do you do that? 2
What factors do you need to consider with parenteral forms? 4 things
Why are delivery devices important? and why? what type of things can happen? 2 reasons
Developing a Stabilizing formulation is Essential
Start with formulation considerations
4 things in the middle
Then you end with?
Protein stabilization using excipients divided into what two things?
Chemical Class
and MOA
Protein stabilization using Excipients
Chemical class 7
MOA 6
Mechanism of Protein stabilization by certain solvent additives
Examples of stabilizing Solvent Additives 3
Common view? Stabilization properties are not due to? 2 other things
Mechanism of Protein Stabilization by Certain Solvent additives
When sucrose is preferntially excluded from the surface of proteins what happens?
Which type of protein has more surface area?
According to Le Chats principles?
What do proteins do to overcome thermodynamically unfavorable conditions?
Non- Ionic surfactant minimizing?
What is an example of this?
Formulation stresses affecting protein aggregation
3 roles
Role of: Formulation varriables, interfaces, and processing
Formulation stresses affecting protein aggregation
Role of Formulation variables 3 things
- Different Classes of?
- Protein?
- Multi-use?
Role of interfaces 3 things with examples
- Liquid to
- Liquid to
- Liquid to
Role of Processing 3 things with examples
- Operations?
- Keeping something still?
- When you are giving it
Drug Labels: Selected sections that comment on Storage and Stability
- Simponi must be?
- Do not use beyond?
- Do not?
- Do not?
- Simponi is provided in?
- Simponi doesnt contain?
- When should you not use the solution?
Sterile prep of protein drugs and IV Admin
Sterile processing during manufacturing of protein drugs usually involves?
Sterile handling may involve? 2 things
Stability within?
Route of Admin for FDA approved mABs
So what types of routes are most common
IV, Sub Q, other
most to least
IV delivery and protein stability
Setup varies in 4 ways
- ___ and ___ rate
- Size of
- __
- __
IV bags 2
Different? and Different types of?
Admin kits 2
Different types of? and Different?
Examples of Variables to Consider during IV admin of Protein Therapeutic DRugs
What I just said but examples
Regulatory Guidelines
ICH-M4Q
USP797
Address proper reconsitution
Compatibility of Protein drugs during IV admin
3 things
- Manufacturers test for compatibility so carefully review dosing and admin instructions to know:
- What to use
- And the need for?
- Need to know what it looks like?
- Need to know?
Compatibility of Protein drugs with other delivery devices (PUMPS)
- Reports of adsorption of protein to tubing in IV infusion: 3 things
- What could the compatibility affect? 2 things
- Considerations should be followed just like?
3
Compatibility of New formulations designed for at home use
2 brand names
One is Lyapholized and one is a solution
What are some issues that at home use can cause for stability
Examples of commercial products high protein concentration SUBQ delivery 6
Whats the point to developing High Concentration mAb formulations?
Sub Q admin typically requires?
- mAb range?
- How is the SubQ injection limited?
- How is at home use facilitated?
What are 5 pharmaceutical challenges involved?
- If it will disolve
- If it is too?
- Realistic?
- Stability in?
- _____ related to 2nd point
Stability challenges to Develop [high] liquid mAbs in prefilled syringes
2 things
- Proteins in what type of formulation?
- These are usually?
- Solubility limite? mg/ml
- 3 issues
- Compatability of ___ protein formulation with?
- Componenets of?
- Silicone and Tungten
- What type od device?
Reversible self association of mAbs at high protein concentration
What are the interactings between the mAb monomers that allow them to be reversible?
3 one is obvious
Example 1 of mAb RSA
Example 1 continued
Why do we care about RSA od therapeutics? Big ass chart
