433 - Midterm 1 Flashcards
Compounded Sterile Products
CSPs
Sterile Drugs
Injections
Irrigations
Pulmonary Inhalations
Opthalmics
Implants
What type of Pressure?
Airflow is flowing INWARD (into hood or room)
and
vented to the outside
NEGATIVE PRESSURE
Required for Hazardous drug prep.
Buffer Area at least < Iso 7
Ante area that opens into NEG-ressure room < iso 7
What ISO must be the CRITICAL AREAS ?
(hood / closest to sterile drugs)
ISO 5
When to CLEAN the PEC?
primary Engineering Control = Hood / isolator
Iso Class 5
Beginning of each Shift
Before & after a batch
After Spills
Anytime CONTAMINATION is suspected
How often do we clean
Counters / Work surfaces / Floors
DAILY
How often do we clean?
Walls / Ceiling / Shelves
MONTHLY
BSC = Chemo Hood
Type of Hood
NEGATIVE PRESSURE hood
used to prepare Hazardous CSPs
Isolators = Glove Boxes
Type of Hood
Completely enclosed type of PEC
2 Types:
CAIs = Positive Pressure, for non-hazardous drugs
CACIs (containment)
NEGATIVE pressure for HAZARDOUS DRUGS
IVLFZ
Integrated Verical Laminar Flow Zones
Type of Hood
HEPA FILTER IN CEILING
over stainless steel work tables
“open Architecture”
SVP vs LVP
Small <100mL
Large >100mL
Where are HAZARDOUS DRUGS prepared?
VERTICAL BSC
in
NEGATIVE PRESSURE FASCILITY
USP 800 = Hazardous Drugs
RED SHARPS WASTE
SHARPS = RED
Needles / Syringes
Broken Ampoules / Vials
WITH or WITHOUT drug remaining
Black Waste
Pharmaceutical / Drug Waste
RED BIOLOGICAL WASTE
Blood / Human Products
Yellow Waste
Yellow = HAZARDOUS DRUGS
ALL material that were in the hood while compounding
Outer gown materials too
When can Drug go into general trash?
- *<3%** of drug remaining
- *intact glass can go into general trash**
Broken Glass w/ <3% drug can go into glass trash
More Drug –> Pharmaceutical Black WAste
More drug in glass –> Sharps container
Incompatibility
When 2+ ingredients interact causing an
UNDESIRABLE / ADVERSE AFFECT
VVVV
Product +/- Efficacy
Ex.
Precipitation Reaction
INSTABILITY
When a compound
UNDERGOES DEGRADATION
Ex.
Rotting Food –> no longer edible
TNA
Total Nutrient Admixture = TNA
aka TPN = 3 in 1 infusion
PN + IV Fat Emulsion
IVFE considerations
IV Fat Emulsion = Lipids
Can CRACK with:
freezing or heating
HIGH pH
contact with HIGH CONCENTRATIONS OF DEXTROSE
Seperate Dextrose & lipids
Order of Mixing for TPN
LIPIDS & DEXTROSE SEPERATE!
PROTEIN IN BETWEEN
MULTIPLE VITAMIN NEAR LAST
due to yellow color
- *Phos + Calcium**
- *also Avoid MAG Sulfate (do not DIRECTLY mix)**
Calcium Phosphate Solubility Curve
- *Concentration BELOW the curve = OKAY**
- *Safety Zone Area**
Curve will shift up into the Danger Zone Area
As pH increases (acidic) from AA’s
Physical Incompatibilites
that can lead to PRECIPITATION
Dilution of non-aqueous solutions
Mixing of APIs formulated at VARYING pH
Mixing of SALTS
Charged SURFACTANTS
+ Protein or +Preservative
HYDROSCOPICITY
is also a physical incompatibility
Chemical Incompatibilities
Hydrolysis
Oxidation
Isomerization / POLYmerization
Complexation / Combination
Decarboxylation
Zero Order Reaction
Half Life & Shelf Life
ZERO ORDER
t1/2 = 1/2 A0/k
ts = 1/10 A0/k
DEPENDS ON A0 = Starting Amount
&
LINEAR
First Order Reactions
Half Life & Shelf Life
FIRST ORDER
t1/2 = ln(2) / k
ts = ln(10/9) / k
Starting amount DOES NOT matter
EXPONENTIAL DECAY
Suspensions
Zero or 1st order?
Thought to be First order
but…
ACT AS ZERO ORDER REACTION
API in the solution is going to degrade over time
Water Vs API
STARTING AMOUNT MATTERS
Definition of Half Life
Point when
90%
of API is remaining
Unless therapeutic index is close to 1 & more stringent dosing is needed
Unless TOXIC or differentially active products are produced
Solution
Zero or 1st Order?
FIRST ORDER
doesnt matter the starting amount
Effect of BUFFER Concentration
COULD EITHER INCREASE OR DECREASE
If….
- *Faster degradation = lower shelf life**
- *↑[Buffer] –> ↑K**
vvvvv
INCOMPATIBILITY
pH & Temperature
Chemical Incompatibility
CAN DO EITHER!
Sometimes the Buffer won’t freeze
VVV
Acidic environment –> degrade API –> ↓Shelf Life
Even though we expect dropping temperature to increase shelf life / stop degradation
Antioxidant & Salt Forms
Chemical Incompatabilities
Antioxidants can be ADDED to address incompatibilities
SALT FORMS MATTER
determine the particular shelf life
Charged Molecules
Physical Incompatibilities
Charged Molecules = MUCH MORE SOLUBLE
Sometimes use this to keep API in solution
pH for Phos-Calcium
Physical Incompatibilities
LOWER pH is BETTER
pH controls what Phos-Calcium precipitate is formed
SOLUBILITY CONTROL
mixing is bad –> cause pH imbalance –> precipitation
Preservative + Surfactants
Precipitation
Physical Incompatibility
Charged Surfactants can result in
PRECIPITATION
of exipients or API
High Concentration + Charged States
Protein + Surfactant
PRECIPITATION
Physical Incompatibility
Surfactants MASKS charges on protein
VVV
Allows protein to COME TOGETHER
Charged AA regions = hydrophylic
& hydrophobic regions come together
VVV
PRECIPITATE
Eutetic Mixtures
Physical Incompatibilities
LIDOCAINE + DECANOIC ACID
Solid + Solid –> LIQUID
can use as a positive as well though
HYDROSCOPICITY
is ALSO a physical incompatibility
What Affects
i = Van’t Hoff’s Factor
Influenced by:
MOLALITY which is affected by CONCENTRATION
at a greater Molality (greater concentration)
VVV
i = greater than theoretical value
- *Colligative Properties** of Solutions
- *DEPEND ON WHAT?**
Vapor Pressure lowering
Boiling Point ELEVATION
Freezing Point depression
Osmotic Pressure
RATIO OF:
# of Solute Particles
# of Solvent Molecules (mass of solvent)
in solution
Osmotic Pressure
Pressure that is PUT ON WATER to
Move it from 1 side to another
When is it VITAL to have ISOTONIC products?
PARENTERALS
Opthalmic
IV / SC
Rectal / Vaginal
in contact DIRECTLY w/ cells
Relationship between
Tonicity & Osmolarity
Tonicity is dependent on # of particles in solution
- *TONICITY =/= Osmolarity**
- but is NEARLY equivalent*
Osmolarity & Osmolality
can be used to
PREDICT TONICITY
Colligative Properties
DEPEND ON WHAT?
# of PARTICLES in a SOLUTION
Solubility of
NON-Electrolytes vs ELECTROLYTES
Non-Electrolytes –> one particle
STRONG ELECTROLYTES
VVV
Complete Dissolution
Electrolytes ideally dissociate
upon solubilization based on # of ions in the molecule
Do Electrolytes + Non-Electrolytes
follow IDEAL COLLIGATIVE PROPERTIES?
NO
Electrolytes + non-electrolytes
DO NOT follow IDEAL colligative properties
IsoOsmotic Solutions
can be CREATED by WHICH METHODS?
FREEZING POINT DEPRESSION
NaCl EQUIVALENT
MIXING METHODs
USP 797
Describes the MINIMUM standards to be followed when preparing compounded STERILE human & animal DRUGS
Standards BEYOND USP 797
are defined by the facility
Products that are REQUIRED to follow
USP 797
Anything sterile –> goes INTO BLOOD STREAM
Injections / Irrigations (internal)
Opthalmics / Inhalations (not sprays)
Baths/soaks for LIVE organs / tissues
Implants
Hazardous Drugs = 800
Radiopharmaceuticals = 825
Who DOESN’T have to follow 797?
Non-Hazardous CSPs used WITHIN 1 HOUR
Propietary bag & Vial systems
must be admin IMMEDIATELY after docking/activating
Allergenic Extracts
must STILL proper ASEPTIC TECHNIQUE
ACPH
Recertification every 6 mo or after room changes
Airflow testing
Hepa Filter Integrity
Total particle count
PEC smoke study
Airflow is measured in the # ACPH = Air changes per Hour
OPPOSITE
Iso Class 8 > 20 ACPH
Iso Class 7 > 30 ACPH
Room guage must not read <0.02 inch water pressure
Beyond Use Dates = BUD’s
- *Date & Time** after which admin of product must
- *NOT BEGIN**
“How long the product is STERILE”
Time starts from the time compoinding is INITIATED
Based on risk of developing microbial contamination
BUD =/= Experiation Dat
Low Risk level
BUD = 48 Hours @ room temp
used to determine BUD along with Categories
Iso Class 5 PEC
Pec is also inside ISO Class 7 buffer area
<3 containers // < 2 entries into a container
90% of preps are in low risk
Low Risk w/ 12 hour or less BUD
used to determine BUD along with Categories
- *Iso class 5 PEC**
- *NOT LOCATED IN ISO CLASS 7 AIR**
Sinks should be adjacent to PEC
no hazardous compounding
Medium Risk
BUD = 30 Hours @ room Temp
used to determine BUD along with Categories
Same as low risk
Iso Class 5 PEC
PEC is also in ISO Class 7 buffer area
BATCH OR BULK COMPOUNDING
mixture with > 3 containers // 5 doses from bulk // TPN
High Risk
BUD = 24 hours @ room temp
used to determine BUD along with Categories
Materials exposed to air < Class 5 for > 1 hour
Personnel improperly garbed
Use of non-sterile starting materials
Must be STERILIZED prior to administration
Category 1 CSP vs Cat 2 CSP
KNOW DIS
Cat 1 CSP
- PEC NOT required to be in classified area*
- *<12 hour BUD**
Cat 2 CSP
PEC REQUIRED to be in a CLASSIFIED AREA
= CLEAN ROOM
Non sterile = 1 day BUD
Sterile = 4 Day BUD
SIngle Dose Vial COnsiderations
Punctured OUTSIDE of ISO CLASS 5 air
= use within 1 hour
Punctured INSIDE of Iso Class 5 PEC
use within 6 hours
USP 800 Sterile Compounding
Still follows ALL 797 Guidelines
- *CSTD is RECOMMENDED** during compounding
- *but is REQUIRED during ADMIN**
Buffer Room Guidelines:
- *HVAC –> vented EXTERNALLY**
- *Negative Pressure** (0.01 - 0.03 water column to adj rooms)
Hood Guidelines:
HVAC + Extenal Vent
MINIMUM > Iso Class 5 BSC or CACI (not CAI)
2 gloves, no need for 2 of others
