* Beyond-Use Date (BUD)
*
“The date or time after which a compounded
sterile preparation (CSP) shall not be stored or
transported. The date is determined from the
date or time the preparation is compounded”
*
Southwestern Clinical Seminar
March 7-9, 2014
* Have Fun
* Review <797> Pharmaceutical Compounding
* Hand Sanitizer
* Math Review
* What is 797 about?
* Prevent harm to patient
* Outlines conditions and practices to reduce
exposure to:
* Microbial contaminations
* Excessive bacterial endotoxins
* Variability in intended strength
* Unintended chemical & physical contaminants
* Quality of ingredients in compounding sterile
preparations (CSP)
*
*
*As per the FDA
* Microbial Contamination Risk Levels
“Compounding does not include mixing, reconstituting,
or similar acts that are preformed in accordance with
the directions contained in approved labeling provided
by the product’s manufacturer and other manufacturer
directions consistent with the labeling”
(e.g. amoxicillin 250mg/5ml suspension)
* Low-Risk Level CSP
* Medium-Risk Level CSP
* High-Risk Level CSP
*Arizona Board of Pharmacy
* Current Good Manufacturing Practices
*
- CFR 21 210 - 211
*
* Medium-Risk Level CSP
* Low-Risk Level CSP
* Compounded and aseptic manipulation entirely
within ISO Class 5 or better air quality using only
sterile ingredients, products, components and
devices
* Only transfer, measuring & mixing NOT more than
3 commercially manufacture sterile products &
NOT more than two entries into any one sterile
container or package (eg bag, vial)
* Multiple individual or small does of sterile products are
combined or pooled to prepare a CSP that will be
administered either to multiple patients or to one
patient on multiple occasions.
* Process includes complete aseptic manipulations other
than the single-volume transfer
* Process requires unusually long duration, such as that
required to complete dissolution or homogeneous
mixing
*
*
* Medium-Risk Level CSP
* Low-Risk Level CSP cont’
* Manipulations are limited to aseptically opening
ampuls, penetrating disinfected stoppers on vials
with sterile needles and syringes and transferring
sterile liquids in sterile syringes to sterile
administration device, package containers of
other sterile products and containers for storage
and dispensing
* Proper storage before administration
* Exposed to controlled room temperature not more
than 30 hours
* Not more than 9 days at cold temperature and for 45
days in solid frozen state between -25 degrees and -10
degrees
* Examples
* TPN – manual or automated
* Filling reservoirs of injections and infusion devices
with more than three sterile drug products and
evacuations of air from those reservoirs before the
filled devices is dispensed
* Transfer of volume from multiple ampuls or vials into
one or more final sterile containers.
*
* Low-Risk Level CSP cont’
* Proper storage before administration
* Exposed to controlled room temperature not more than 48
hours
* Not more than 14 days at cold temperature and for 45 days in
solid frozen state between -25 degrees and -10 degrees
* Examples
* Single-volume transfers of sterile forms from ampuls (sterile
filtered), bottles, bags and vials using sterile syringes with
sterile needles, other administrations devices and other
sterile containers.
* Simple aseptic measuring and transferring with not more
than three packages of manufactured sterile products,
including an infusion or diluent solution to compound drug
admixtures and nutritional solutions
*
*
* High-Risk Level CSP
* Nonsterile ingredients, including manufactured products
not intended for sterile routes of administration (e.g. oral)
are incorporated or a nonsterile device is employed before
terminal sterilization.
* Exposure to air quality worse than ISO Class 5 for more
than 1 hour
* For example:
* Sterile contents of commercially manufactured
products
* CSPs that lack effective antimicrobial preservatives
* Sterile surface of devices and containers for the
preparation, transfer, sterilization and packaging of
CSPs
*
* High-Risk Level CSP
* Proper storage before administration
* Exposed to controlled room temperature not more than 24 hours
* Not more than 3 days at cold temperature and for 45 days in solid
frozen state between -25 degrees and -10 degrees
* Examples
* Dissolving nonsterile bulk drug and nutrient powders to make
solutions that will be terminally sterilized
* Exposing the sterile ingredients and components used to prepare and
package CSPs to room air quality worse than ISO Class 5 for more
than 1 hour
* Measuring and mixing sterile ingredients in nonsterile devices before
sterilization is performed
* Assuming, without appropriate evidence or direct determination,
that packages of bulk ingredients contain at least 95% by weight of
their active chemical moiety and have not been contaminated or
adulterated between uses
* Bacteriostatic
* Defined as - Agent that stops bacteria from
reproducing
* Hand sanitizer works as Antiseptic Agents per CDC
Antimicrobial spectrum and Characteristic of Hand-Hygiene Antiseptic Agents*
Source- MMWR Recommendations & Reports 10/25/2002 / 51(RR16);45
*
*
Summary of Risk Levels
Risk
Levels
CSP
ISO
Class
Transfer,
measuring &
mixing
Manipulation
limits
Storage /BUD
Low
Class 5
ore than 2 entries
into one product
<48hrs room temp
From ampuls,
vials via syringes 14 day cold
to admin device 45 days frozen
Medium
Class 5
Multiple doses
combined to
admin multiple
occasions
Multiple
transfers
<30hrs room temp
3 day cold
45 days frozen
High
Class 5
Nonsterile
ingredients, use
of non sterile
device
Exposure to <
class 5 > 1 hr
<24hrs room temp
3 day cold
45 days frozen
* Alligations
* Using Alligations as A Math Technique
*
* Using alligations to solve problems that involve
* Hand Sanitizer
diluting or concentrating liquids
* Review the steps
* Review Additives
* Demonstrations
The Problem:
The Lab has 500ml bottle of 99% Isopropyl Alcohol in Carbomer
Suspension. You have been asked to prepare a concentration of 66%
(v/v) final volume 60ml. H2O is the diluent. How much of the 99%
(v/v) Isopropyl Alcohol in Carbomer Suspension & how much water
is needed to make 66% (v/v) Isopropyl with a final volume of 60ml.
*
*
2.
* Use the following five steps:
1.
2.
Determine “Haves” & “Wants.”
The Problem:
Determine whether diluting or concentrating a
liquid.
a)
If diluting, find the diluent. It’s either 0% or some %
lower than the wanted %.
b)
If concentrating, find the pure drug. It’s either 100%
or some % higher than the wanted %.
Determine “Haves” & “Wants.”
The Lab has 500ml bottle of 99% Isopropyl Alcohol in Carbomer Suspension. You
have been asked to prepare a concentration of 66% (v/v) final volume 60ml. H20 is
the diluent. How much of the 99% (v/v) Isopropyl Alcohol in Carbomer Suspension
& how much water is needed to make 66% (v/v) Isopropyl with a final volume of
60ml.
Answer:
Have - 99% Isopropyl Alcohol in Carbomer Suspension & Water as diluent
concentration = 0%.
Want: 66% (v/v) Isopropyl, final volume of 60ml.
*
*
3.
* Continuation steps 3-5:
3.
Set up “grid system” and fill in the values in the
“H” (Haves) & “W” (Wants) columns. Perform
diagonal subtractions.
4.
Set Ratio Proportions using values from “U/P/R”
(use, parts, ratio) column.
5.
Calculate out the ratio proportions.
Set up “grid system” and fill in the values in the “H”
(Haves) & “W” (Wants) columns. Perform diagonal
subtractions.
Review of Step 2:
Have - 99% Isopropyl Alcohol in Carbomer Suspension & Water as diluent
concentration = 0%.
Want: 66% (v/v) Isopropyl, final volume of 60ml.
H
W
U/P/R
66 Parts of 99%
99%
66%
*
1.
Determine whether diluting or concentrating a
liquid.
a)
If diluting, find the diluent. It’s either 0% or some %
lower than the wanted %.
b)
If concentrating, find the pure drug. It’s either 100%
or some % higher than the wanted %.
33 Parts of H2O
0%
99 Total wanted
4.
*
Set Ratio Proportions using values from “U/P/R”
(use, parts, ratio) column.
Using r/p (ratio proportions) to determine the amount (X) of 99% Isopropryl
66
99
=
X mL
60 mL
Answer: Want to dilute a solution. Diluent is water.
The Problem:
The Lab has 500ml bottle of 99% Isopropyl Alcohol in Carbomer Suspension. You
have been asked to prepare a concentration of 66% (v/v) final volume 60ml. H20 is
the diluent. How much of the 99% (v/v) Isopropyl Alcohol in Carbomer Suspension
& how much water is needed to make 66% (v/v) Isopropyl with a final volume of
60ml.
What is the% of water? Answer: 0%.
*
Using r/p to determine the amount (Y) of water
33
99
=
Y mL
60 mL
*
5.
Calculate Out the ration proportions
Using r/p (ratio proportions) to determine the amount (X) of 99% Isopropyl
66 = X mL
99
60 mL
(99)(X) = (66)(60 mL)
X = 40 mL
99% Isopropyl in
Carbomer Suspension
Using r/p to determine the amount (Y) of water
33
99
=
Y mL
60 mL
(99)(Y) = (33)(60 mL)
Y = 20 mL of water
*
This is the proof:
The definition of 99%(v/v) Isopropyl = 99 mL pure alcohol
100 mL total volume
Have:
40 mL of 99%(v/v) Isopropyl
99 mL
=
100 mL (TV)
X mL
40 mL
X = 39.6 mL
of pure Isopropyl in
Carbomer Suspension
and we have 20 mL of water added for TV of 60 mL
39.6 mL
60 mL
X 100 = X%
66% Isopropyl in
Carbomer Suspension
& H2O (60 mL TV)
*
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*