Transcript PARENTERALS: COMPOUNDING STERILE FORMULATIONS

CHAPTER 9
PARENTERALS: COMPOUNDING
STERILE FORMULATIONS
CHAPTER OUTLINE
• Compounding Sterile
Formulations
• Special Considerations
• Regulatory Oversight
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LVP Solutions
SVP Solutions
Special Solutions
Administration Devices
Laminar Flow Hoods
Biological Safety Cabinets
Clean Rooms
• Aseptic Techniques in Hoods &
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Cabinets
Working with Vials
Working with Ampules
Syringes & Needles
Filters
Quality Assurance & Infection
Control
Parenteral Incompatibilities
Units of measurement
Review
SPECIAL REQUIREMENTS OF STERILE
FORMULATIONS
• Sterile
– NOT a relative term
– Free from bacteria and other microorganisms
• No particulate material
• Pyrogen–free
• Stable for its intended use
• Many require physiological pH
• Many require osmotic pressure similar to blood
REGULATORY OVERSIGHT OF STERILE
COMPOUNDING
• Compounding is regulated by state boards of
pharmacy.
• USP (United States Pharmacopeia – a non-profit
organization) has federal authority to set
compounding and manufacturing standards.
– USP chapters < 1,000 are enforceable by the FDA.
• Some states accept USP standards as the state’s
regulations. But some states have different
regulations.
REGULATORY OVERSIGHT OF STERILE
COMPOUNDING
• Chapter <795> deals with nonsterile compounding.
• Chapter <797> deals with sterile compounding.
– CSP – compounded sterile preparation
– The intent is to prevent harm and fatality resulting
from
 microbial contamination
 excessive bacterial endotoxins
 large errors in the strength of correct ingredients
 and the presence of incorrect ingredients.
COMPOUNDING STERILE FORMULATIONS
• Injectables
– IV, IM, SC, ID
• Ophthalmic
• Intranasal
• Otic
• Inhalation
TYPES OF STERILE INTRAVENOUS
SOLUTIONS – LVPs
• Large-volume parenterals (LVPs) : > 100 ml
– Correct electrolyte imbalance
– Vehicle for administering other drugs
• Available in plastic bags and glass bottles
• Common LVP solutions:
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–
–
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Dextrose 5% in water
0.9% NS (sodium chloride) solution
Ringer’s solution
Lactated Ringer’s solution
TYPES OF STERILE INTRAVENOUS
SOLUTIONS - LVPs
 Ports
Administration port
Medication port
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TYPES OF STERILE INTRAVENOUS
SOLUTIONS - SVPs
• Small volume parenterals (SVPs): < 100 ml
– primarily used for delivering medications
– ampules, prefilled syringes, single or multidose vials
• Additive - a drug that is added to a parenteral
solution
• Admixture - the resulting solution when a drug is
added to a parenteral solution
TYPES OF STERILE INTRAVENOUS
SOLUTIONS - SVPs
• Ready-to-mix systems
– Add-Vantage®
– Add-a-Vial®
– Mini-Bag Plus®
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TOTAL PARENTERAL NUTRITION (TPN)
SOLUTIONS
• Nutritional support to patients who are unable to take
in adequate nutrients
• Contains macro- and micronutrients
– Macronutrients: dextrose and protein
– Micronutrients: electrolytes, vitamins, and trace
elements
– Lipid emulsion: fatty acids and calories
• Available in 2 or 3 liter sizes
• Administered via the subclavian vein over 8-24 hours
DIALYSIS SOLUTIONS
• Dialysis - the passage of small particles
through membranes byosmosis
• Peritoneal dialysis – a solution placed into
and emptied from the peritoneal cavity to
remove toxic substance from the body
– hypertonic
– administered several times a day
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IRRIGATION SOLUTIONS
• Sometimes called “splash” solutions
• Container size: > 1,000 ml, designed to empty
rapidly
• Surgical irrigation solutions - bathe and moisten
body tissue, dressing, or wash instruments
• Urological irrigation solutions - maintain tissue
integrity or remove blood to maintain a clear field
of visi on
ADMINISTRATION DEVICES –
ADMINISTRATIONS SETS
 IV administration set
• device used to deliver IV fluids to patients
• have many variations.
• Flow rate control
– clamp on administration set
– drip chamber
– controller
– combination controller/pump
– volume control chamber
ADMINISTRATION DEVICES – POSITIVE
PRESSURE PUMPS
• Cassette pump
– for ambulatory patients
• Syringe pump
– very useful in neonatal, infant, and critical care
applications
• Peristaltic pump
– micro-pulses
– uses tubing that is reinforced with silastic insert
• Elastomeric pump
– balloon-like reservoir
ADMINISTRATION DEVICES – PIGGYBACKS,
HEPARIN LOCKS
• A piggyback is a SVP admixture that is administered through an
existing IV line.
– Usually over a short time, from 30 minutes to 1 hour
• Heparin Locks
– Used if no primary LVP is available
– Heparin is used to fill tubing, preventing blood clots.
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publisher.
LAMINAR FLOW HOODS (LFH)
• Enclosed work area designed to establish and
maintain an ultraclean work area
– Air is pushed through a high efficiency particulate air
(HEPA) filter that removes 99.97% of particles > 0.3 µm.
– Air flows over work surface at a uniform velocity
(i.e., laminar flow) of 80-100 ft./min.
– USP Chapter <797> requires LFH to be ISO Class 5
environments.
• no more than 3,520 particles ≥ 0.5 µm
• Both horizontal and vertical designs
LAMINAR FLOW HOODS (LFH) –
HORIZONTAL HOOD
HEPA filter
air out
laminar flow viewed
from above
intake filter
air in
blower
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LAMINAR FLOW HOODS (LFH) – VERTICAL
HOODS
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BIOLOGICAL SAFETY CABINETS
• Designed differently than laminar flow hoods
• Protects personnel and the environment
• Class II, Type A1 cabinets are recommended for
preparing chemotherapy agents.
CLEAN ROOMS
• Sterile compounding must be housed in an area
isolated from the main traffic – a clean room.
• Need an ISO Class 7 environment
– no more than 352,000 particles ≥ 0.5 µm per cubic
meter of air
– have unrestricted air flow
– only designated personnel in space
• If the clean room is ISO Class 5 environment,
LFH/biological safety cabinets are not required.
ASEPTIC TECHNIQUES
• Sum total of methods and manipulations required to
minimize the contamination of CSPs
• Can’t say this loudly enough: Working in a LHF or biological
safety cabinet does not, by itself, guarantee the sterility of
CSPs. ASEPTIC TECHNIQUES MUST ALSO BE USED.
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Publishing Company. May not be copied, re-used,
reproduced, or re-transmitted without express
written permission from the publisher.
PREPARING LHF (AND BIOLOGICAL
SAFETY CABINETS)
• Turn the hood “on” at least 30 minutes
before use.
• Maintain a designated clean area around
the hood.
• Thoroughly clean the hood.
– Use the correct cleaning order for the interior
surfaces of the hood.
ASEPTIC TECHNIQUE – COLLECT SUPPLIES
• Gather all the necessary materials for the
operation and make sure they are
– not expired
– free from particulate matter such as dust
– and have no leaks -- check by squeezing plastic
solution containers
• Only essential objects and materials
necessary for the product preparation
should be placed in the LFH.
ASEPTIC TECHNIQUE – GROWING AND
HAND WASHING
• All jewelry should be removed from the hands
and wrists.
• Put on lint-free garments and barrier clothing.
– Note: there is a proper sequence for dressing.
• Wash hands and forearms thoroughly.
– use antibacterial soap
– work soap under fingernails
• interlace fingers
• wash up to elbows
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re-used, reproduced, or re-transmitted without express written permission from the
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ASEPTIC TECHNIQUE – WORKING IN A LFH
• Work without interruptions.
• Place nonsterile objects downstream from
sterile objects inside the LFH.
• Place larger objects toward the front of the LFH
away from the HEPA filter.
• Do not eat, drink, talk, or cough in the LFH.
ASEPTIC TECHNIQUE – WORKING IN A LFH
• Plan a work area at least 3 inches from the
back and 6 inches from the front of the LFH.
– Make sure nothing obstructs the flow of air
from the HEPA filter over the work area.
– Nothing should pass behind a sterile object and
the HEPA filter in a horizontal airflow hood or
above a sterile object in a vertical airflow hood.
• Swab with an alcohol wipe all surfaces that
require puncture. Use a new wipe with
each surface.
WORKING WITH VIALS
• Two types of vials used to make admixtures
– for drugs already in a solution
– for drugs in a lyophilized powder that must be
dissolved in a dilute to make a solution.
• To withdraw a solution from a vial
– Introduce a volume of air into the vial equal to
the volume of solution to be removed .
– Draw the solution into a syringe and remove air
bubbles.
– Remember that the plunger and the tip of the
syringe are sterile and must not be touched.
CORING
• Coring is when a needle damages the rubber closure of a
parenteral container causing fragments of the closure to fall
into the container and contaminate its contents.
• To prevent coring
– Place the vial on a flat surface and position the needle point
on the surface of the closure at about a 45° angle.
– Put downward pressure on the needle while gradually
bringing the needle to an upright position (90° angle).
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AMPULES
• An ampule is a single-dose-only drug container.
• Gently tap the top of the ampule to bring the
medication to the lower portion of the ampule.
• Clean the neck with an alcohol swab; then grasp
the ampule between your thumb and index finger
at the neck while keeping the swab still in place.
• Forcefully snap the neck away from you.
AMPULES
• To withdraw solution from an ampule, tilt
the ampule to about 20° down and use a
filter needle or filter straw to remove the
solution.
• Position the needle or straw on the shoulder
area of the ampule. Place the beveled edge
against the side of the ampule.
SYRINGES AND NEEDLES
• Basic parts of a syringe
– barrel - tube that is open at one end and
tapers into a hollow tip at the other end
– plunger - piston-type rod with a slightly
cone-shaped stopper that passes inside
the barrel
– tip - attachment point for a needle
• Common types: Slip-Tip®, Luer-Lock®,
and Eccentric tips®.
• Available in sizes from 1 ml to 60 ml.
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from the publisher.
SYRINGES AND NEEDLES
• Basic parts of a needle
– hub – at one end of the needle;
attaches to the syringe
– shaft – long stem of the syringe
– bevel – angled end of the syringe forming a
point
• Needles are made of stainless steel or aluminum.
– Needle lengths range from 3/8” to > 3 inches.
– Needles come in gauges ranging from 27 to 13
(higher the gauge number, the smaller the
lumen size).
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from the publisher.
FILTERS
• Two types of construction
– depth filters – twisting channels through the filter
material
– membrane filters – small pores of a uniform size in
filter material
• Found in many types of packaging
– round plastic holder
– flat plastic holder such as a final filter
– inside a needle such as a filter needle
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from the publisher.
FILTERS
• Depth filter – filters a solution either pulled
into or expelled out of a syringe
– but not both ways with the same filter
• Membrane filters – filters only a solution
expelled out of a syringe
QUALITY ASSURANCE (QA) - FACILITIES
• USP Chapter <797> requires every compounding
facility has to have a QA program.
• Environmental Quality and Infection Control Plans
– certification of ISO class
– monitoring of airborne particulates and
microbiologicals.
– cleaning and sanitizing compounding areas.
– hazardous materials regulations.
QUALITY ASSURANCE (QA) –
COMPOUNDING OPERATIONS
• Proper preparation of product
• Inspection and final check of product
– container integrity and leaks
– product cloudiness, particulates, color
• Sharps disposal
– Sharps are objects that might puncture or cut the skin
of anyone who handles them.
– Containers should be easily identified, leak proof,
puncture proof, and be able to be sealed permanently.
PARENTERAL INCOMPATIBILITIES
• Incompatibilities
– drug and drug incompatibility
– drug and IV solution incompatibility
– drug and parenteral container incompatibility
• Characteristics of incompatibilities
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color change
hazy appearance
precipitations
gas evolution
chemical degradation
PARENTERAL INCOMPATIBILITIES – HOW
TO MINIMIZE
• Use solutions promptly after preparation.
• Minimize the number of drugs that are added at
one time.
• Check references or package inserts if additives
– will result in a very high or very low solution pH
– contain calcium, magnesium, or phosphate salts
– contain acetate or lactate
PARENTERAL INCOMPATIBILITIES –
CONTRIBUTING FACTORS
• pH (degradation, precipitation)
• Light (degradation)
• Temperature (stability)
• Dilution (proper concentration may avoid
incompatibility)
• Buffer capacity (change pH)
• Time (degradation)
PARENTERAL INCOMPATIBILITIES –
CONTRIBUTING FACTORS
• Filters
– Inline filters cause 90% reduction in nitroglycerin.
• Solutions
– Amphotericin B is not compatible in NS.
• Chemical Complexation
– Calcium reduces tetracycline activity.
– Needles or filters containing aluminum should not be used
with Cisplatin-AQ.
• Plastics
– Some drugs may bind to plastics.
– Plasticizers can leach out of plastics – may bind to some
drugs.
UNITS OF MEASUREMENT
• Molarity
– A mole is the number of grams numerically equal to the
molecular weight of the drug.
• Osmole
– Equal to the molecular weight of the drug divided by the
number of ions formed when a drug dissolves in solution.
• Osmole = molecular weight
# of ions
UNITS OF MEASUREMENT
• Equivalent
– Equal to the molecular weight of the drug divided by the
valence of the ions formed when a drug dissolves in
solution.
• Equivalent weight =
molecular weight
valence
• Percentage weight per volume (w/v)
– Refers to drug’s weight per 100 ml if drug is a solid
– Refers to drug’s volume per 100 ml if drug is a liquid.
• Solid: % =
weight (gm)
100 ml
• Liquid: % =
volume (ml)
100 ml
UNITS OF MEASUREMENT
• International Units (IU)
– Drug potency varies between biological sources.
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penicillin
insulin
heparin
vitamins