Transcript compounding of sterile products - LaGuardia Community College

Aseptic Technique and USP 797
 Definitions
 Asepsis is the state of being free from the presence of
pathogenic microorganisms.
 Septicemia is the presence of microorganisms in the
blood
 Septic shock is the condition of overwhelming infection
of the blood by septicemia.
 Aseptic technique strives to maintain surgical asepsis.
(meaning complete sterility and lack of endotoxin )
USP 797 rules
 United States Pharmacopeia 797 chapter on
compounding of sterile products (CSP) was
published in the 27th revision to USP on January 1st,
2004
 USP 797 is applicable to all facilities where
compounded sterile products (CSP) are made, stored
and sent to the patient
 USP 797 applies to the aseptic technique used to make
CSPs as well as the environment in which it is done
Issues addressed by USP 797
 Aseptic techniques used to prepare CSP
 Evaluation of personnel in USP 797 standards
 Growth medium testing (media fill test with soy/casein)
 Fingertip testing
 Cleanroom and antiroom construction
 Class of BSC
 Air cleaness, defined as ISO5 or in old terminology
class 100
Microbial Risk Levels in USP 797
 Low risk CSP
 Made under ISO5 conditions
 Involves aseptic transfer of manufacturer based sterile products using
sterile equipment (i.e Needles and syringes) to compound IV
admixtures.
 Does not involve open systems and no more than 3 components
 Medium Risk CSP
 More than three components are a part of the IV admixture (i.e TPN’s)
 CSP don’t contain antimicrobial preservative and product is given over
more than 2 days
 Complex preparation involved
 High Risk CSP
 Compounding of manufactured ingredients that are non sterile and
then performing terminal sterilization
 Performing compounding in conditions outside ISO5
Risk Levels and Expiration Dating
 Low Risk CSP
 48 hrs at room temperature
 14 days under refrigeration
 45 days frozen state
 Medium Risk CSP
 30 hrs at room temperature
 7 days at refrigeration
 45 days at a frozen state
 High Risk CSP
 24 hours at room temperature
 72 hours refrigerated
 45 days at a frozen state.
Hospital Compounding
 For the most part you may be preparing only low or
medium risk CSP’s
 Example of a low risk CSP
 Making a 250 ml SVP with 1.25 gram of vancomycin under
ISO5 conditions
 Example of a medium risk CSP
 Compound a triple mix TPN with additional additives of
insulin, multiple vitamin injections, and other electrolytes
 Example of high risk CSP
 Compounding a sterile ophthalmic solution from a
manufactured product that is not sterile and passing solution
through a 0.22 micron filter several times
Air Quality and Cleanness
 ISO stands for international organization for
standardization
 ISO was formed in 1947 in Geneva Switzerland
 Provides different levels of air quality cleanness
 ISO 5 means no more than 100,000 particulates that
are 0.1 micrometer or larger per cubic meter of air. By
contrast, room air is classified as ISO9 which is no
more than 1,000,000,000 particulates per cubic meter.
(a ten thousand fold difference)
Anteroom
 Usually consists of a storage area, an area for records,
computers and printers, an buffer area for gowning
 Has ISO class 8 standard (not restrictly required)
 Has a sink equipped with surgical scrub soap
(Chlorhexidine), and has handfree or pedal activated water
systems
 Has the following characteristics:
 Smooth walls with panels locked and sealed
 Vinyl covered floor with seals heated together
 Joints and junctures between walls and ceilings must be
chauked with no visible cracks.
Clean Room





The room where the LAFW hoods are located
Means same physical characteristics as anteroom
Has ISO class 8 standard
No sinks and floor drains
If facility only compounds low and/or medium risk CSPs
the clean and ante rooms need not be separated. Area
immediately next to LAFW hoods is called buffer area
 If all risk levels are compounded clean and ante rooms
must be separated.
 Must be maintained as a positive room air pressure
environment if separated.
Structure of USP 797 defined
Cleanroom
Cleanroom:
Positively pressured,
Houses BSC
Vinyl flooring
ISO 8 environment
Negatively pressured for
chemo or hazardous
drugs
Anteroom
Vinyl flooring
Maybe ISO 8
environment
Contains sink for hand
hygiene
Gowning apparel
REST OF THE
PHARMACY
Maintaining of ante and
Cleanrooms
 Cleaning requirement
 BSC or LAFW = beginning of shift, before each preparation, 30
minutes into the procedure, when surface is visible contaminated
 Cleaning of all floor surfaces daily from the buffer area outwards,
from the clean room out to anteroom.
 Countertops: daily
 Cleaning and disinfection of all shelving surfaces at least monthly
 Walls, Ceilings: monthly
 Documentation of such maintained
 Cleaning solvent required by USP for ISO5 and countertops:
 Isopropyl Alcohol USP 70%
Laminar Air Flow Hoods and
Workbenchs
 LAFH and workbenchs are designed to blow parallel sheets of sterilized clean
air over a work surface
 The hood is usually washed and disinfected with 70% isopropranol by a
pharmacist at the beginning and end of the shift. Washing is from top to
bottom of the hood and back to front in the direction of laminar flow.
 HEPA filters remove over 99% of particles, including microorganism 0.3
microns or larger. When cleaning the HEPA filter grill do not spray the filter
always spray the sterile gauze pads and clean the surface of the grill
 If the HEPA Laminar flow hood is turn off for any reason then it must be turn
on for at least 30 minutes before commencing any IV preparation.
 Horizontal Laminar Flow Hood: the HEPA filter is at the back of the hood and
blows laminar air towards the operator
 Vertical Laminar Flow Hoods: the HEPA filter is on the top of the hood and
laminar air flow sheets are blown to the work surface and not to the operator
 Also called a biological safety cabinet
 Must be recertified every 6 months
Biological Safety Cabinets
 Class I open system that draws air from the cleanroom
 Class II air is recirculated through vents in the front and
back and passed though a HEPA filter on the top of the
cabinet back down to the worksurfaces.
 Four types A, B1, B2, and B3
 Type A is not vented to the outside
 Type B1,B2,B3 all provide some or all exhaust to the facility’s
external vent system.
 Class III are completely enclosed system under negative
pressure which are vented. Manipulation by the operator
are with a gloved apparatus through the front of the
cabinet
Biological Safety Cabinets
Preparing to make an IV product
 Enter the antiroom with slow and deliberate movement.
Remove jewelry and tie back loose hair.
 PPE (Personal Protective Equipment) Procedure Order
 Put on shoe coverings (booties)
 Put on head cap
 Put on lint free surgical mask
 Wash hands up to the elbows for 30 seconds and rinse hands
first allowing water to drip down to elbows
 Don lint free surgical coverall (Bunnysuit)
 Don powder free sterile latex gloves
 Enter cleanroom
When in the cleanroom
 Before placing the drug product, IV bag, etc in the BSC
 Clean the BSC



From top to bottom
From the inside outside direction
Clean with 70% isopropyl alcohol
 Clean the surface of all IV vials, IV bags with 70%
isopropyl alcohol
 Sterilize gloves or replace
 Remove all caps to vials. Swab each vial with alcohol





swab from back to front once with swab.
Swab medication port of the IV bag that you will use.
All products should be 6 inches inside the hood.
Arrange materials in such as way as to not block any of
the laminar flow air currents.
Once inside the hood, your hands should not leave the
inside of the hood. If they do you will need to sanitize
your gloves before returning to the hood area.
Always remember not to touch critical areas
 The following are critical areas which must not be
touched.
 All parts of the needle.
 The hub of a luer lok syringe
 The ribs of the piston of the syringe.
 The injection port of the IV bag.
 The rubber entry port of the vial
 Remember, touch is the number one cause of product
contamination.
 Human skin harbors many organisms: Staphylococci,
Streptococci, Actinobacter, Candida, Tricophyton
Rubrum fungi, Pseudomonas, etc.
 Contaminated IV products can cause bacteremia and
fungemia, septic shock and death.
 I will demonstrate aseptic technique in class with
reference to drug manipulation.
The Finished products
 If you are a pharmacy technicians that will be performing
IV admixtures. Always leave the following item for the
RPH to check:
 All vials used in the process
 All syringes used in the process drawn back to the volume you
used.
 All information recorded in the IV prep log book: Patient’s
name, medical record number, drugs, concentrations,
volumes used, lot number and manufacturer’s expiration.
 Assigned a pharmacy expiration date (usually 24 hours at
room temperature)
A great reference to use to determine drug-drug, drug-IV
solution compatibilities is a book called, Trissel’s
Handbook on Injectable Drugs®
Common causes of physical and chemical incompatibilities
are:
 Drugs mixed in low pH solutions, like D5W
 Drugs mixed in hypertonic solutions, like D5WNS
 Drugs mixed in incorrect IV mediums. Such drugs are not
compatibility in the PVC container of an IV bags; these drug
are mixed in glass IV containers. A class example is
nitroglycerin which is used for patients with acute MI.
 Drugs mixed with other drugs that “complex” each other.
Type of Parenteral Products
 Injections are products that are already mixed into
solutions. Solutions are pH buffered, sterile, pyrogen free
with methylparabens, benzyl alcohol preservatives
 Packaged in
 Vials
 Ampules
 Single doses Vials
 Have no preservatives
 Once open, use and discard
 Multiple Doses Vials
 Have preservatives
 Once open 28 days exp
Courtesy of :http://www.hospira.com/en/products_and_services/drugs/FENTANYL_CITRATE
Type of Parenteral Products
 For Injections : products that are lyophilized powders
that require addition of water to form a solution a
given concentration. Usually these products are single
dose
Courtesy of :http://www.hospira.com/en/products_and_services/drugs/CEFTRIAXONE
IV Labeling
 Labeling rules are governed by the state, non governmental
agencies guidelines (JCAOH, USP797)
 Include the following:








Patient’s name, location in institution, MRN
Drug and strength
Base fluid
Name of other additives and quantities of
The intended time of administration of drug
Rate of administration if LVP (or hang time if SVP)
Prep by field and Verified by field
Product expiration field
 In addition a nursing label may be attached detailing:
 When product was “hung” (i.e. started)
 By whom the product was hung
IV products that require special
handling
 Some IV products require special handling and
precautions
 These drugs are loved to be tested by PTCE
 Paclitaxel (Taxol®) requires non PVC IV tubing
 Nitroglycerin Injection requires glass container for IV
and non PVC IV tubing
 Nitroprusside Injections requires the same as
nitroglycerin and the IV tube must be covered by a light
resistant material to prevent from light degradation
 Lipid Emulsion also require non PVC, non DHEP IV
tubing
Parenteral Therapy
 Intravenous Therapy (IV) involves injecting a medication





directly into the blood via venous access devices
IV products must be sterile and pyrogen free with no
particulate matter in the solution
Intramuscular Injection (IM) involves injection into the
large belly of a muscle
Subcutaneous Injection (SubQ) involves injection in the
hypodermis of the skin
Epidural Injection involves injection next to the dura mater
of the spinal cord
Intrathecal Injection involves injection into the
subarchnoid space of the meninges
 ALL THESE PRODUCTS MUST BE STERILE AND
PYROGEN FREE
 IN ADDITION EPIDURAL AND INTRATHECAL
INJECTION MUST BE PRESERVATIVE FREE IN
ADDITION TO STERILITY
Preservative free is required for
epidural injections
Coutesy of:
http://www.drugs.com/pro/duramorph.htm
l
Type of IV Therapy
 IVP or Intravenous push involves insert a needle and
syringe directly in a VAD (vascular access device)
 IV Infusion
 Large Volume Parenteral involves a large volume of fluid
given IV over a long period of time (1,000 ml)

Often called a “drip” with given continuously
 SVP or a small volume parenteral is a small volume of fluid
(50 ml to 100 ml) given IV over a short period of time (10
minutes or so)

Often called an intermittent infusion
 IVPB, intravenous piggyback is a type of SVP that is infused
along with a LVP
Source: wikimedia commons page
Venous Access Devices
 Catheters that are inserted into the antecubital vein and is
called a peripheral line
 The catheter is usually made of Teflon (a material that does
not trigger phlebitis)
 Entry into the vein is evident with blood in the flash back
chamber
 The hub of the catheter is a female connection that is made to
receive a connection called a male luer lok connection
 Often a short tube with a access port called a heparin or saline
lock is attached to the hub of the catheter to provide a port to
inject IV therapy
 http://www.youtube.com/watch?v=s-vTzQkUQd8
 A larger catheter that is inserted into the larger vein of
the neck (commonly the subclavian vein) is commonly
called a “central line”
 Central Lines are used to deliver TPN, and larger
volumes of hypertonic fluids rapidly. Also it is meant
to deliver vasopressor agents in the ICU
 Types of Central Catheters


Hickman Lines are tunneled to the jugular vein under the skin
and is used to deliver chemo and other potent drugs.
Broviac lines are similar and used in children
Primary IV Infusion Sets
 These infusion sets are made of PVC and DHEP and
meant to carry the fluid from an IV bag to the hub of a
IV catheter or a saline/Heparin lock
 This tube consists of a piercing pin, drip chamber, an
in line filter and several Y site IV ports for the
administration of the secondary IV fluids through a
piggyback system
 Used to deliver a LVP over several hours
Secondary IV administration sets
 Secondary IV administration sets are used to deliver
smaller volumes of drug containing fluids of about 50100 ml
 In general this tube has a piercing pin, drip chamber,
and a roller clamp and male luerlok. In general this
tubing has no Y site ports
 The connection is attached to the Y site of a primary
line
INFUSION SET UP
1 liter of NS or D5W
Addition port
Administration set port
Drip chamber
http://www.youtube.com/watch?v=N0rCuC2XE1U
Intravenous Solutions and tonicity
 IV solutions that are “isotonic” to plasma have the same tonicity as plasma (300
mOsmoles/L) and cause no shift in body fluid compartments
 0.9 % Na CL is “normal saline” and has a tonicity of 300 mOsmoles/L
Vascular
Compartment
Interstitial
Compartment (fluid
around organs)
Intravenous Solutions and tonicity
 IV solutions that are “hypertonic” to plasma have the higher tonicity than plasma and
cause a shift in body fluid compartments from the Interstitial space to the vascular
compartment causing this compartment to become volume over loaded with heart
failure and increase pressure on the brain
 3% NaCl (1000 mOsmole/L)
 14% NaCL (5,000 mOsmole/L)
 23.4 % NaCL (8,000 mOsmole/L)
Interstitial
Compartment
(fluid around
organs)
Vascular
Compartment
Intravenous Solutions and tonicity
 IV solutions that are “hypotonic” to plasma have the lower tonicity than plasma and
cause a shift in body fluid compartments from vascular space to Interstitial compartment
but also fluid shifts into red blood cells causing them to burst and triggering a hemolytic
anemia
 0.225 % NaCL
 Free sterile water
Interstitial
Compartment
(fluid around
organs)
Vascular
Compartment
Intravenous Solutions
 Normal saline (0.9%) is one of the most common because its isotonic
with plasma. Isotonic means equal to it in terms of “tonicity”. i.e.
plasma has a tonicity valve of about 290 mOsm. Normal saline or NS is
about 300 mOsm.
 Tonicity of a solution determines if bodily fluid shifts will occur
 Dextrose 5% in water (D5W) is the second most common type.
Consists of glucose or dextrose in water to make it 285 mOsm (isotonic)
 D5WNS is a combination of the two and is used when some calories in
the form of glucose is needed. Hypertonic (580 mOsm about) but it is
Ok to use.
 3 % Saline (NaCL) is only used to treat certain brain conditions. Very
hypertonic and can cause death if used improperly
 23.4% saline (NaCL) used only in certain rare conditions and in small
volumes. Will cause death if used improperly (remember Emily Jerry?)