biopharm exam 2 - biologics

storage temperature

vaccine potency (effectiveness) is strongly affected by

cold temperature (2-8°C)

most vaccines are stored at _______

potency

storing vaccines at too high a temperature can decrease _______

true

T/F: freezing can decrease potency

a weak response or no response

loss of potency may result in _____

cold chain

______ must be maintained to ensure vaccine quality

true

T/F: we should use separate dedicated refrigerator and freezer units 'if possible'

false (freeze-thaw cycling)

T/F: it is ok to use frost-free freezers for vaccines

true

T/F: we should not store any vaccine in a dormitory-style or bar-style combined refrigerator/freezer unit under any circumstances

0.5°C

document storage temperature with a logger unit in each refrigerator and freezer with accuracy of _______

middle level shelves

we should keep products in original package on _______

true

T/F: we can fill the top and bottom shelves and door shelves with water bottles to maintain temperature after door is opened and closed

-do not freeze the diluent (only vaccine product/vial)

-do not store items directly under the cooling vent

-leave space between the products in freezer to allow cold air circulation

CDC advice for frozen products

weekly

when maintaining the temperature log, we should review the data ______ to identify any problems.

shortest expiration time

use the vials with the _______ first to maintain fresh supplies.

true

T/F: if offs-site delivery is necessary, deliver in a portable freezer with temperature logging device

primary structure

______ is the amino acid sequence of an individual peptide chain

covalent bonds

primary structure is maintained by _______ between amino acids.

secondary structure

_______ describes regions of alpha helix, beta sheet, or random coil configurations

false (non-covalent bonds)

T/F: secondary, tertiary, and quaternary structure is primarily maintained by covalent bonds.

tertiary structure

______ is the overall 3-D configuration of individual peptide chains

non-covalent

________ include hydrogen bonds, ionic bonds, and van der waals or hydrophobic interactions

quaternary structure

________ is the overall 3-D configuration of a protein composed of 2 more individual peptide chains.

normal (native)

the ______ conformation is required for protein drug activity.

quaternary

_______ means a specific tertiary or quaternary structure of a peptide or protein

denature

______ means to change the 2°, 3°, and/or 4° structure of a protein to an unnatural or inactive conformation.

aggregate

_____ means to stick together due to non-covalent interactions between molecules

false (may be reversible or irreversible)

T/F: denaturation and aggregation are irreversible

potency

irreversible changes decrease the _________ of the product.

amino acids; 3° and 4°

protein denaturation can lead to aggregation by exposing _________ that are normally hidden in the interior of the _________ structure

albumin

egg white contains mostly the protein ______ in water.

false (irreversible)

T/F: heating albumin causes a reversible change in the protein structure

stability

______ means the extent to which a product maintains its original characteristics over time during storage.

false

T/F: a stable product changes over time

destructive changes

an unstable product exhibits _______ over time.

-physical state

-storage temp

-solution pH

-protein concentration in solution

-concentration of additives

-preparation procedures

protein stability depends on several factors

denaturation and aggregation

Freezing, storing the product at too high a temperature, or causing foaming in a protein can lead to _________.

freezing

_______ is the crystallization of water molecules out of the solution

true

T/F: during freezing, the dissolved solutes remain in the liquid phase

decreases; increases

during the process of freezing, the liquid volume ______ and the concentration of all solutes _______.

cyroconcentration

_______ means the increase in dissolved solute concentration that occurs during freezing of an aqueous solution.

cryoconcentration in monoclonal antibody

the following image is showing

peptide bonds; 1°; irreversible

protein molecules can be sheared by adjacent ice crystals as they grow during freezing. this breaks ______ in the protein chain. ______ structure is destroyed. this is _______

true

T/F: increasing solute concentration alters non-covalent interactions

increases

protein concentration ______ due to decrease in liquid volume.

true

T/F: denaturation and aggregation may be reversible or irreversible when the product thaws

additive

repeated freezing and melting produce _________ destructive effects.

frost-free

_______ freezers cause freezing-melt cycling

-20°C

frozen products should be maintained at ________

0°C

frost-free freezers periodically heat the cooling coil above _____ to remove ice from coils.

true

T/F: products inside the freezer may approach 0°C and partially melt with each heating cycle then re-freeze when the temperature returns to -20°C

how long the product is stored

the number of melt-freeze-melt cycles a product is exposed depends on _______

cryoconcentration

each cycle exposes some of the drug in the vial to _______

true

T/F: effects on product quality are additive with each melt-freeze-melt cycle

cryoprotectant

protein products that are shipped and stored frozen usually contain a

cryoprotectant

a _________ is an excipient to maintain protein structure during the industrial freezing procedure

industrial freezing

______ is much faster and much gentler on protein structure than you do in the pharmacy.

false

T/F: it is okay melt and then refreeze and administer a protein product that are shipped and stored frozen.

false

T/F: with a cryoprotectant, it is impossible to destroy the protein structure with the slow freezing used in the pharmacy.

kinetic energy

higher temperature causes all dissolved molecules to have higher ________

weak noncovalent bonds; secondary, tertiary, and quaternary

higher kinetic energy can overcome ________ responsible for __, ___, and___ structure.

true

T/F: conformation changes can occur when the temperature is too high

increase; oxidation and hydrolysis

chemical reaction rates ______ with temperature. resulting is faster _____ and _____.

sulfur-containing; aromatic amino acids

______ and _____ are more susceptible to degradation.

false (may change all levels)

T/F: chemical degradation may change only some levels of protein structure.

primary

change in an amino acid, even if chain does break is a change in _____ structure

true

T/F: change in primary structure may cause a change in higher level structure

irreversible

chemical change is generally _______

true

T/F: chemical degradation may induce denaturation and/or aggregation

false

T/F: products that are shipped and stored at refrigerated temperature is okay to use if frozen.

stored frozen until use

products that are shipped and stored frozen are designed to be

light

products that are shipped and stored at refrigerated temperature should be protected from

20-25°C; 15°C and 30°C

controlled room temperature is ________ with brief excursions allow between ______ as long as that do not adversely affect product quality

-protected from heat and light

-stored at stated temperature range

products that are shipped and stored at room temperature should be

foam

_____ is air or gas bubble in a liquid mixture

gas

the foam volume is mostly _____

liquid solution

the bubble wall is composed of the _______

surfactants

foams are stabilized by ______ in the liquid phase.

surfactant

a ____ is a chemical compound the concentrations at interfaces.

interface

the ______ is a bubble is where the gas an liquid phases meet.

surfactants

most proteins behave as ______ in aqueous solution

protein molecules at the gas-liquid interface experience __________ as compared to protein molecules dispersed liquid phase.

volume of foam produced

the extent of protein damage is proportional to the

vigorous agitation

_____ promotes foaming

parenteral administration

_______ is administered for most proteins

large

biologics typically have ______ molecular weights

false (very slowly)

T/F: proteins diffuse very fast across GI mucosa

-stomach pH

-proteases in gastric and pancreatic secretions

Proteins degrade when given orally due to ______ and ______

-IV

-IM

-SC

-intranasal

-inhalation

common routes of administration for biologics

solution

drug molecules must be in ________to distribute through the body

blood or lymph vessels

proteins given by IM or SC injection can be take up into _______ or ______

slower

rate of protein uptake into capillaries is _______ as protein size increases.

clefts; fenestra

protein molecules can enter capillaries through _____ and ______

fenestra

_____ or holes in endothelial cell structure

intercellular gaps

______ where endothelial cells meet

intercellular cleft

this is showing

fenestra

this image is showing

return extracellular fluid to the blood

one function of lymph system is to ______

true

T/F: lymph vessels have larger gaps in their walls than capillaries

false (more quickly)

T/F: protein molecules can be taken up more slowly into lymph vessels than capillaries