Texas Tech Pharmacy Course Covers Sterile Compounding

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Course Administered By:

Council For Pharmaceutical Education (ACPE) as a provider of continuing
Pharmaceutical
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STERILE COMPOUNDING AND PREPARATIONS

A Knowledge Based Program for Technicians
By
Jeff Blackburn, MBA Healthcare Administration, C.Ph.T.
ACPE No. 0096-9999-09-020-H04-T

Total number of pharmacy continuing education hours: 6 hours (0.6 CEUs)
Release Date: 4/6/2009

Expiration Date: 4/6/2012
Course Cost:
$19.00 (to be paid at time of testing)
Average time to Complete:
Approximately Six hours including testing
Course Value:
Six Contact Hours
Reading:
52 Pages
Final Exam:
50 Questions
Completion Requirements:
Answer 70% of question correctly

Complete Evaluation
Sterile Preparations
Course Objectives
1. Discuss the role of the C.Ph.T. in sterile compounding.
2. Review sterile preparation formulations.
3. Describe some of the issues related to large volume parenteral solutions.
4. Describe some of the issues related to small volume parenteral solutions.
5. Discuss the equipment and facilities related to sterile preparations.
6. Review the procedures related to sterile compounding.
7. Discuss the procedure related to proper aseptic technique.
8. Review quality control procedures related to sterile preparations.
Table of Contents
I.
Overview of Sterile Compounding and the Role of the C.Ph.T.
II.
Sterile Preparation Formulation
III.
Sterile Preparation Facilities and Equipment
IV.
Laminar Flow Hoods
V.
Perenteral Solutions
a. Large Volume
b. Small Volume
VI.
Uses for Sterile Compounding
VII.
Aseptic Technique
VIII.
Policies and Procedures for Compounding Sterile Preparations
IX.
Packaging
X.
Labeling Sterile Preparation
XI.
Storage
XII.
Quality Control and Maintaining Integrity
I. Overview of Sterile Compounding and the Role of the C.Ph.T.

When drugs need to be injected, any one of several routes can be used to administer the
drug. The most common injectable routes of administration are intravenous (in the vein),
intramuscular (in the muscle), and subcutaneous (in the skin).
The compounding of sterile preparations is an integral part of any health-system setting.
While the majority of perenteral products are prepared using commercially available
medications and diluents solutions, pharmacy departments still perform intravenous
manufacturing. The reasons for this vary greatly, but can include:
Special patient populations such as pediatrics, geriatrics, or the terminally ill (pain
management). For these patients, the appropriate strengths for certain drugs may
not be available.
Some patients might be allergic to the diluents and preservatives in commercially

available products.
Some drugs are unstable and require preparation to be dispensed every few days.
A combination therapy that a prescriber desires, but that is not currently

commercially available.
Intravenous Administration
Intravenous administration of drugs has advantages over other routes of administration
because it provides the fastest route to the bloodstream. There are no barriers like skin or
muscle to absorb the drug first, which allow the most rapid onset of action. If someone
cannot take medication by mouth because he is unconscious or vomiting, then
intravenous administration is the best route. Since the inner lining of a vein is relatively
insensitive to pain, drugs that can be irritating if given by another route can be given
intravenously as a slow rate without causing pain. Drugs that can be diluted to reduce
irritation can be given only intravenously because the tissue and skin around the other
routes of administration cannot accommodate large volumes.
There are two types of intravenous administration. The first is an intravenous injection in
which the prepared medication is drawn up into a syringe and administered immediately.
The amount of medication is usually a small volume pushed through an IV line that is
already in place on the patient.
The second type of administration is an IV infusion. Infusions are given to overcome
dehydration, to build up depleted blood volumes, and to serve as an aid for the
administration of medications. An infusion allows a larger volume to be given at a
constant rate, depending on the drug to be administered. Infusions can be administered
continuously or intermittently. Continuous infusions are used to administer larger
volumes of solutions over several hours at a slow, constant rate. Intermittent infusions
are used to administer a relatively small volume over a shorter time at specific intervals.
The Role of the Pharmacy Technician
The above reasons demonstrate why the need for compounding pharmacists will continue
to grow and why the responsibilities and opportunities for pharmacy technicians are also
increasing. As pharmacists become part of a multidisciplinary, multi-skilled team to
provide quality patient care, they rely more and more on pharmacy technicians.
Technicians have now assumed many of the duties that were once performed by the
pharmacist. Once such duty is drug preparation, specifically, compounding and
intravenous drug preparation.
Pharmacy technicians are actively involved in all aspects of pharmaceutical care. The
Scope of Pharmacy Practice Project1 found that 26% of technicians time is spent in
collecting, organizing, and evaluating information. The second most time-consuming
functions (21%) involve preparing, dispensing, distributing, and administering
medications. Another survey, of Georgia technicians, identified what percentages of
hospital technicians prepare certain sterile dosage forms (Table 1 1).2
Table 1 -1
Percentage of Pharmacy Technicians
Who Participate in Sterile
Compounding by Preparation Type
Sterile Dosage Form
Technician Participation
in Extemporaneous
Compounding %
Unit Dose Inj.
60
Large Volume parenteral 81
Admixtures
TPNs
57
IV piggybacks
85
Chemotherapy
31
Narcotic infusions
38
Pharmacy technicians who engage in pharmaceutical compounding must expand their
compounding knowledge and be trained at a higher skill level to perform the
compounding responsibilities of sterile technique properly and safely.
Summary of the final report of the Scope of Pharmacy Practice project. Am J Hosp Pharm, 1994;51:217982.
2
Anderson RJ. Pharmacy technician survey in the state Georgia. Ga J Hosp Pharm. 1993:7(summer):179.
Pharmacy technicians must possess the following basic requirements to participate in

sterile compounding:
A working knowledge of the policy and procedure manuals for compounding,

dispensing, and delivering sterile products.
Adequate training and adherence to hygienic and aseptic techniques.
Access to sufficient reference materials about sterile products.
Knowledge and awareness of the proper methods to store, label, and dispose of
drugs and supplies.
Awareness of how to conduct sterile compounding in an area separate from other
activities.
Knowledge of established procedures for assigning beyond-use dates that exceed
the manufacturer labeled expiration dates.
The level of difficulty of preparing the compounding prescriptions is determined by the

physical properties of the drug being prescribed and the dosage form desired either by the
prescriber or patient. In some cases compounding will be a simple two-step process,
whereas in others it will require extensive knowledge and many steps to perform.
Sterile compounding is an advanced pharmacy technique that requires proper training of
technicians, in addition to their general education. This course is not designed to take the
place of a formal education either in institutional settings or academic programs. It is
merely a review of compounding practices for pharmacy technicians who are currently
working in this area of the pharmacy or for technicians who would like to know more
about the processes. Like all good continuing education, it is intended to expand your
knowledge and reinforce concepts you already know.
One point which must always be remembered, the pharmacist maintains control
over all pharmacy activities. The ultimate responsibility rests with the licensed
pharmacist.

II. Sterile Preparation Formulations
The objective of formulating and compounding sterile preparations is to provide a dosage

form of a labeled drug, in the stated potency, that is safe to use if administered properly.3
This section will explore the professional standards and operating procedures that should
be followed during formulation and compounding. The components, containers, and
closures also are described, as well as the physiologic and physical norms of preparing
formulations for parenteral and ophthalmic use. Stability, incompatibility of drugs,
sterilization methods, labeling, documentation, and end preparation evaluation is
discussed in later sections.
Federal Regulations
When formulating and compounding sterile preparations, the technician must follow both
state laws and Food and Drug Administration (FDA) regulations. State pharmacy
practice acts and board of pharmacy regulations cover these activities. The FDA also
regulates formulation and compounding under adulteration, misbranding, and new drug
provisions of the Federal Food, Drug, and Cosmetic Act (The Act).
Adulteration
Section 501(a)(2)(B) of the Act states that a drug is adulterated if the methods used in,
or the facilities or controls used for its manufacture, processing, packing or holding do
not conform to current good manufacturing practice.4 Technicians who compound
sterile preparations must meet purported norms (what is implied on the label is true).
Purported norms include identity and strength of ingredients, quality, and purity. Failure
to ensure purported norms renders the preparation adulterated and misbranded.
Professional Standards
Bulk, or unformulated, drug substances and added substances, or excipients, must be
stored in tightly closed containers under temperature, humidity, and lighting conditions
that are either indicated by official monographs or approved by suppliers; also the date of
receipt in the compounding facility must be clearly and indelibly marked on each
package of ingredient. After receipt by the compounding facility, packages of ingredients
that lack a suppliers expiration date cannot be used after on year, unless either
appropriate inspection or testing indicates that the ingredient has retained its purity and
quality for use in compounded sterile preparations.
Turco SJ. Composition. In: Turco SJ, ed. Sterile Dosage Forms, Their Preparation and Clinical
Application, 4th ed. Philadelphia, PA: Lea & Febiger; 1994:1127.
4
Food and Drug Administration. Chap 32, Division of Field Regulatory Guidance. Hospital pharmacies
status as drug manufacturer, FDA Guide 7132.06. Washington, DC: Oct 1, 1980.
Written Procedures
Any technician who formulates and compounds sterile preparations should develop and
comply with the following written procedures.
Pharmacies must have a specifically designated and adequate area (space) for the orderly
placement of equipment and materials to be used in compounding. Compounding of
sterile preparations should be in a separate and distinct area from non-sterile
compounding.5
The technician ensures that the sterile components under his supervision meet acceptable
criteria of stability and sterility by:6
Using the oldest stock first and observing expiration dates.
Storing components under the environmental conditions stated in the individual

monographs and/or in the labeling.
Observing components for evidence of instability. Although chemical

degradation ordinarily cannot be detected by the naked eye, some physical
changes not necessarily related to chemical potency, such as change in color and
odor, or formation of a precipitate, or clouding of solution, may alert the
technician of a stability problem. If a component has undergone a physical
change not explained in the labeling, such a preparation is never to be dispensed.
Observing components for evidence of lack of sterility. The presence of

microbial contamination in sterile components cannot be detected visually, but
color change, cloudiness, surface film, or gas formation is sufficient reason to
suspect possible contamination. Evidence that the integrity of the seal has been
violated should make the component suspect of microbial contamination.
Properly handling and labeling preparations that are repackaged, diluted, or mixed
with other products.
Dispensing the proper container with the proper closure.
Sterile compounding equipment must be appropriate in design, size, and

composition so that surfaces contacting components are not reactive, additive, or
adsorptive. These surfaces should not alter the required safety, identity, strength,
quality, and purity of the components.
National Association of Boards of Pharmacy. Good compounding practices applicable to state licensed
pharmacies. Model State Pharmacy Act and Model Rules of the National Association of Boards of
Pharmacy. http://nabp.net ; accessed September 9, 2003.
6
Standard operating procedure: Certificates of analysis of materials used for pharmaceutical compounding.
Internat J Pharma Compound. 2001 (Mar/Apr): 5:147.
As a technician, your work must be checked by a licensed pharmacist.

Dispensing pharmacist must inspect and approve or reject all formulas,
calculations, substances, containers, closures, and in-process materials.
Technicians who compound batches of parenteral preparations must follow a master

formula sheet to reproduce preparations that meet all purported norms.
Components
Components are any ingredient used in compounding, whether or not they appear in the
final preparation (intermediate ingredients). Whenever available, commercially sterile
components should be used. Commercial ingredients should be made in an FDA
approved facility and meet official compendial requirements (contained in a list). If these
requirements cannot be met, an alternative substance must be used.
Vehicles
Vehicles for most liquid sterile preparations have no therapeutic activity or toxicity.
Rather, they serve as solvents or mediums for the administration of therapeutically active
ingredients. For parenteral preparations, the most common vehicle is water. Vehicles
must meet USP (United States Pharmacopeia) requirements.
Water for Injection
Water for injection is purified by distillation or reverse osmosis and is free of pyrogens
(bacterial substance that can produce fever). Sterile water for injection USP is sterilized
and packaged in single-dose containers not exceeding 1000 ml. Bacteriostatic water for
injection is sterilized and contains one or more bacteriostatic agents in a container no
larger than 30 ml.
Sterile water for inhalation is sterilized and packaged in single-dose containers that are
labeled with the full name. As implied, this component cannot be used to prepare
parenterals. Sterile water for irrigation is sterilized and packaged in single-dose
containers with no added substances. Although this component may be packaged in
containers larger than 1000 ml, it is not intended for parenteral use.
Aqueous Isotonic Vehicles
Aqueous isotonic vehicles are often used in sterile preparations. A common vehicle is
sodium chloride injection, a 0.9% solution (also known as normal saline) that is sterilized
and packaged in single-dose containers no larger than 1000 ml. Bacteriostatic sodium
chloride injection is a 0.9% sodium chloride injection that contains one or more
bacteriostatic agents in a container no larger than 30 ml. Sodium chloride irrigation also
is a 0.9% solution; however, it has no preservatives and may be packaged in a container
larger than 1000 ml.
Other isotonic vehicles include Ringers injection, dextrose injection 5%, and lactated
Ringers injection. None of these components is available in containers larger than 1000
ml.
Water-Miscible Solvents
A water-miscible solvent is a solution that can be thoroughly mixed with water. Several
water-miscible solutions are used as a portion of the vehicle in sterile preparations (cosolvents). These solvents, such as ethyl alcohol, liquid polyethylene glycol, and propylene glycol) dissolve drugs with low water solubility. Preparations compounded with
these components are usually administered intramuscularly.7 Examples of drugs in cosolvent formulations include some barbiturates, antihistamines, and cardiac glycosides.
Nonaqueous Vehicles
Nonaqueous vehicles, such as fixed oils, can be used to formulate parenteral preparations,
USP specifies that fixed oils must be vegetable in origin and odorless and also have no
rancid taste.8 Examples include peanut, cottonseed, corn, and sesame oils. Some
vitamins and hormones can only be solubilized in these oils. Also, oil-based parenterals
can only be given intramuscularly.
Solutes
A solute is a component of a solution. In a solution, the dissolving substance is called the
solvent, whereas the dissolved substance is called the solute. Solute chemicals dissolved
in vehicles should be USP grade or better since their contaminants can:
Alter solubility and compatibility of other solutes

Cause catalytic chemical reactions
Cause toxicity of patients
Solutes may be active ingredient or added substances. Added substances can increase
stability or usefulness if they are harmless in their administered amounts and do not
interfere with therapeutic efficacy.
Antimicrobial Preservatives
If a concentration is considered bacteriostatic (preventing bacteria from growing and
multiplying, but not really killing them) a antimicrobial preservative may be added.
Some preservatives, however, have innate toxicity within these concentrations and are
used mostly in ophthalmics and seldom in injectables. Examples include phenylmercuric
nitrate 0.01%, benzalkonium chloride 0.01%, and phenol 0.5%).
7
Avis KE. Levchuk JW. Chapter 41. Parenteral preparations In: Gennaro AR, ed, Remington: the Science
and Practice of Pharmacy, 20th ed. Baltimore, MD: Lippincott Williams & Wilkins; 2000. p 780-806.
8
United States Pharmacopeial Convention. Chapter 1 Injections. In: United States Pharmacopeia 27th
rev./National Formulary 22nd.
10
Benzyl alcohol (usually 0.9%) is commonly used in injectables. In oleaginous (oily)

preparations, no antimicrobial is highly effective. An antimicrobial agent may be
effective in one formula of ingredients but not in another. To select a preservative, an
appropriate reference should be consulted and its effectiveness should be verified. USP
provides a test for the efficacy of antimicrobial preservatives.
pH Buffers
Buffering agents stabilize a solution against degradation. Buffering agents are
formulated at the lowest concentration needed for stability so that they do not disturb the
bodys natural pH. Acid salts such as citrates, acetates, and phosphates are commonly
used as buffers.
Antioxidants
Antioxidants help to prevent oxidation of the component drug. Oxidation is defined as
the interaction between oxygen molecules and all the different substances. Technically,
however, with the discovery of electrons, oxidation came to be more precisely defined as
the loss of at least one electron when two or more substances interact. Those substances
may or may not include oxygen. This can work to degrade the drug/drugs with in the
solution. The most common antioxidants are the sodium and potassium salts of metasulfite and sulfite ions. However, the choice of salt depends on the pH of the system to
be stabilized. Metabisulfite is used for low pH values, bisulfite for intermediate pH
values, and sulfite for high pH ranges.
Chelating Agents
Chelating agents enhance the effectiveness of antioxidants. They form complexes with
trace amounts of heavy metals, thereby eliminating the catalytic activity of metals during
oxidation. The most commonly used chelating agent is edenate sodium.
Tonicity Agents
The tonicity agents are used to adjust the composition of the formulation to the desired
isotonic range. Some examples include glycerin, mannitol, sorbitol, sodium chloride, and
other electrolytes.
Solubilizers
When performing sterile compounding, technicians must know the solubility
characteristics of drug substances, since they must possess some solubility to elicit a
therapeutic response. Polyethylene glycols 300 and 400, and propylene glycol, glycerin,
and ethyl alcohol frequently are used. However, toxic levels of these solvents must be
avoided as well as amounts that make the preparation too viscous (thick or sticky) for
parenteral use.
11
Emulsifiers
Some drugs are minimally soluble in water. Emulsifiers are used to suspend tiny oil
globules in water to create an emulsion that contains a uniformed concentration of the
active drug throughout the volume of the liquid. One example is a soybean oil and water
emulsion manufactured with egg yolk. An example of an active drug is propofol that is
dissolved in soybean oil which is emulsified into a concentration.
Containers
Containers are defined as that which holds the article and is or may be indirect contact
with the articles. The closure is part of the container.9 All containers for sterile
preparations must be sterile, free of both particulate matter and pyrogens. These
containers should not interact physically or chemically with formulations to alter their
required strength, quality, or purity. Containers must also permit inspection of their
contents.
Single or Multiple Dose Containers
Sterile, single-dose containers are intended for parenteral, inhalation, irrigation, octic, and
ophthalmic administration. Examples are prefilled syringes, cartridges, ampuls, and vials
(when labeled as single-use).
Multiple-dose containers permit withdrawal of successive portions of their contents
without changing the strength, quality, or purity of the remaining portions. Sterile,
multiple-dose containers may be used for preserved parenterals, ophthalmics, and octics.
Glass
Glass is the most popular material for sterile preparation containers. USP classifies glass
as Type I (borosilicate glass), Type II (soda-lime-treated glass), Type III (soda-lime
glass), or NP (soda-lime glass unsuitable for parenteral containers). Different glass types
vary in their resistance to attack by water and chemicals. For pharmaceutical containers,
glass must meet the USP test for chemical resistance. Because most pharmacy personnel
do not have the time or facilities to perform glass chemical interaction studies, they
should use only Type I glass to minimize sterile preparation compatibilities.
United State Pharmacopeial Convention. General notices and requirements. In: United States
Pharmacopeia, 27th.
12
Plastic
Plastic polymers can be used as sterile preparation containers but present three problems:
1. Permeation of vapors and other molecules in either direction through the
container.
2. Leaching of constituents from the plastic into the preparation.
3. Sorption of drug molecules onto the plastic.
Plastics must meet USP specifications for biological reactivity and physiochemicals.
Most plastic containers do not permit ready inspection of their contents because they are
unclear. Most plastics also melt under heat sterilization.
Closures
Rubber closures must be rendered sterile, free from pyrogens and surface particles. To
meet these specifications, multiple washings and autoclavings are required. An autoclave
heats sterilizing solutions above their boiling point to sterilize medical instruments.
Closures are made of natural, neoprene, or butyl rubber. Thus, the rubber sealing of a
vial or the plug in a syringe is a complex material that can interact with the ingredients of
a formula. Rubber closures also are subject to coring. Therefore, you should consult the
literature standards when selecting a rubber closure for sterile preparations.
Parenteral Formulations
Pharmacists and technicians will compound a wide variety of sterile formulations in
different settings. These formulations will include products administered by injection,
such as:
Intravenous (IV) medication is injected directly into the vein

Intramuscular (IM) medication is injected directly into a large muscle
Subcutaneous (SC) also know as hypodermic injection; medication is injected
into the tissue under the skin
Intradermal (ID) medication is injected into the substance of the skin
Intrathecal medication is injected into the spinal canal
Epidural medication is injected through a catheter placed in the epidural
space, which is the outermost part of the spinal canal.
There are also other sterile products, which may be administered by the following routes:
Inhalation medication is inhaled through the mouth

Intranasal medication is inhaled through the nose
Ophthalmic medication administered through the eye
13
Parenteral preparations are classified into six general categories:10

1. Solutions read for injection.
2. Dry, soluble preparations ready to be combined with solvent before use.
3. Suspensions ready for injection.
4. Dry, insoluble preparations ready to be combined with a vehicle before use.
5. Emulsions.
6. Liquid concentrates ready for dilution prior to administration.
Most compounded sterile parenteral preparations are aqueous solutions (first category).
Other categories usually require the equipment and expertise of a licensed pharmacist. In
addition to using appropriate vehicle, solvent, and container, you must ensure that the
final aqueous solution maintains the appropriate physiological and physical norms.
Large Volume Parenteral Solutions
Large-volume parenteral (LVP) solutions are commonly stored in plastic or glass.
Solutions for injection must be sterile, and contamination must be prevented by using
aseptic techniques. LVP solutions are available in a variety of sizes (250 mL, 500 mL,
1000 mL).
Examples of LVP solutions with additives, manufactured in standard concentrations,
include:
Aminophylline
Dopamine
Lidocaine
Nitroglycerin
Potassium
In some cases, the preparation of LVPs by the pharmacist or technician depends on the
drug and intended use. The preparation of LVPs in the pharmacy must always follow
aseptic technique (discussed later). Common examples of LVPs in use include:
Dextrose Injection, USP

Dextrose and Sodium Chloride Injection
10
Avis KE, Levchuk JW. Chapter 41. Parenteral preparations. In: Gennaro AR, ed. Remington: The
Science and Practice of Pharmacy, 20th ed. Baltimore, MD: Lippincott Williams & Wilkins: 2000. p. 780806.
14
Amino Acid Injection

Mannitol Injection, USP
Ringers Injection, USP
Lactated Ringers Injection, USP
Sodium Chloride Injection, USP
These solutions are usually administered by intravenous infusion to replenish body fluids,
electrolytes, or provide nutrition. They are usually administered in volumes of 100 mL to
1 liter amounts (and more) per day by slow intravenous infusion with or without
controlled-rate infusion systems.
When a patient is being maintained on parenteral fluids for several days, simple solutions
providing adequate amounts of water, dextrose, and small amounts of sodium and
potassium generally suffice. When patients are unable to take oral nutrition or fluids for
several days or weeks, solution of higher caloric content may be used (total parenteral
nutrition). These admixtures are very useful for:
Patients receiving chemotherapy

Anorexic patients
Pediatric patients
Small-Volume Parenteral Solutions

Small-volume parenteral (SVP) solutions can be either directly administered to a patient
or added to another parenteral formulation. Additive parenteral solutions are called
admixtures. SVP solutions can be supplied in different forms:
Prefilled syringes
Glass or plastic vials sealed with a rubber closure
Ampules
Plastic minibags or piggybacks
Physiological Norms
When injectable solutions are formulated, every effort should be made to mimic the
bodys normal serum values for pH and tonicity and to create a pyrogen-free preparation.
pH
The term pH is used to describe the degree of acidity of a solution. pH values range from
0 to 14, with values below 7 representing greater acidity of the solution, while values
above 7 represent less acidity or greater alkalinity. A solution having a pH of 7 is neither
acid, nor alkaline; it is considered neutral. Plasma in our body is about 7.4, and solutions
should try to stay around that number, pH is another characteristic that cannot be seen,
but can be tested after it is prepared. Normal human serum pH, a logarithmic measure of
the hydronium ion concentration in solution, is 7.4. Drugs that are acids or bases or their
15
salts sometimes must be buffered to a pH near normal (e.g., 3-8) to prevent pain or tissue
damage.
Tonicity
Another characteristic that also cannot be seen is isotonicity. An isotonic solution has the
same concentration as red blood cells. Isotonic IV solutions minimize patient discomfort
and damage to red blood cells. Stinging caused by either a hypertonic (shrinking of red
blood cells) or hypotonic (swelling of red blood cells) solution is not experienced with an
isotonic solution. IV solutions should be as close to isotonic as possible. A good
reference point to remember is that 0.9 percent sodium chloride injection and 5 percent
dextrose injection are both approximately isotonic.
Any chemical dissolved in water exerts a certain osmotic pressure, which is the pressure
exerted by a solution necessary to prevent osmosis into that solution when it is separated
from the pure solvent (i.e., a solute concentration related to the number of dissolved
particles per unit volume).11 Blood has an osmotic pressure corresponding to sodium
chloride 0.9%; thus, its common name is normal saline. Normal saline is said to be
isosmotic with blood ad other physiologic fluids.
In the medical setting, the term isotonic is used synonymously with isosmotic. A
solution is isotonic with a living cell if no net gain or loss of water is experienced by the
cell and no other change is present when the cell contacts that solution. Very hypotonic
(containing a low concentration of solute relative to another solution) IV preparations can
cause hemolysis (the destruction or dissolution) of red blood cells. Very hypertonic
(contains a high concentration of solute relative to another solution) injections can
damage tissue and cause pain on injection. The greater the volume of solution to be
injected, the closer the parenteral preparation should be to isotonicity.
Pyrogenicity
Pyrogens are contaminants that are unacceptable in final compounded sterile
preparations. Pyrogens are fever-producing endotoxins from bacteria. As large proteins,
pyrogens are not removed by normal sterilization procedures and can exist for years in
aqueous solution or dried form.
The sources of pyrogens in sterile preparations are:
Aqueous vehicles
Equipment
Containers and closures
Chemicals used as solutes
Human touch
11
Reich I, Poon CY. Sugita ET. Chap. 18. Tonicity, osmoticity, osmolality and osmolarity. In: Gennaro
AR, ed. Remington: The Science and Practice of Pharmacy. 20th ed. Baltimore, MD: Lippincott Williams
& Wilkins; 2000. p. 246-62.
16
If sterile water for injection is the vehicle, the risk of pyrogens in water is eliminated.
Equipment, containers, and closures can be decontaminated by dry heat or by washing or
soaking with acids and bases. Touch contamination is most easily prevented with proper
aseptic technique (discussed later).
Physical Norms
Particulates
Parenteral solutions must be free of particulate matter mobile, undissolved solids not
intended for sterile preparations. Examples include lint, cellulose12 and cotton fibers,
glass, rubber, metals, plastics, undissolved chemicals, rust, diatoms, and dandruff.
Sources of particulate matter are:
Vehicles and solutions

Environment
Containers and closures
Personnel
A careful choice of components, containers, and closures can minimize particulate

contamination. Also, filtration can remove particles and bacteria from sterile
preparations.
Stability
Stability of parenteral preparations must be assured so that patients receive the intended
dose. Hydrolytic (decomposition of a chemical compound) and oxidative degradations
are the most common forms of instability but rarely show as cloudiness or color changes.
The rate of hydrolysis13 may be affected by storage temperature or pH of the solution.
Oxidation is affected by temperature, pH, exposure to light, oxygen concentration of the
solutions, and impurities.
Because numerous factors affect the stability of drug molecules, parenterals from bulk
chemicals should use a short beyond the use date. The choice of packaging also is
important for perenteral drug stability.
Impurities
Heavy metals (like lead and mercury) are also to be minimized in sterile preparations.
Heavy metals can be toxic and can catalyze the degradation of active ingredients and
preservatives. Introduction of these impurities is most likely when non-sterile; raw
materials are used in compounding.
12
Cellulose is one of many polymers found in nature. Wood, paper and cotton all contain cellulose.
Hydrolysis is a chemical reaction during which one or more water molecules are split into hydrogen and
hydroxide ions. It is the type of chemical reaction that is used to break down certain polymers, often
increasing the strength or pH.
13
17
III. Sterile Preparation Facilities and Equipment

The following equipment is essential for sterile compounding:
Syringes and needles

Alcohol pads
Large-volume parenteral (LVP) solutions.
Small-volume parenteral (SVP) solutions
Ampules or vials
Laminar airflow hoods
Refrigerators (with thermometers)
Freezers
Sinks with hot and cold water
Automated compounding devices
Disinfectant cleaning solutions
Disposable, lint-free towels or wipes
Disposable gowns, caps, masks, and sterile gloves
Sharp containers
Computer systems
Shelving
Carts
Stainless steel furniture
Laminar Flow Hoods

Sterile products should be prepared in Class 100 environments, which can contain no
more than 100 particles (a small piece or portion of anything, such as microorganisms)
per cubic foot. These particles are 0.5 microns (or larger) in size. Laminar flow hoods
are commonly used to achieve a Class 100 environment.
Laminar flow hoods are designed to reduce the risk of airborne contamination during the
preparation of IV admixtures by providing an ultra-clean environment. The most
important part of a laminar flow hood is a high-efficiency, bacteria-retentive filter,
commonly called a HEPA (high-efficiency particulate air) filter. Room air is taken into
the unit and passed through a pre-filter to remove relatively large contaminants such as
dust and lint. The air is then compressed and channeled up behind and through the
HEPA filter, where virtually all bacteria are removed. The purified air then flows out
over the entire work surface in parallel lines at a uniform velocity. The orientation of the
direction of airflow can be horizontal or vertical. Great care must be exercised to prevent
cross-contamination from one operation to another, especially with horizontal laminar
airflow. Vertical laminar airflow hoods are used to prepare drugs for chemotherapy.
18
Vertical Laminar Airflow Hoods

With vertical flow, room air enters at the top of the unit and is channeled through the
bacteria-retentive filter (which forms the ceiling of the unit) and down vertically across
the work surface area. As with the horizontal flow hood, this type of vertical flow hood
is not suitable for chemotherapy drugs. Although they protect the drug product from
microbial contamination, they do not protect personnel or the environment from the
hazards of the drug agents. These laminar flow hoods blow air across the work surface
toward the operator and into the work environment. Drug particles or aerosols of these
hazardous agents can easily contaminate both workers and the work environment.
Biological Safety Cabinets
Since horizontal laminar-airflow hoods blow air toward the operator, vertical laminar
airflow hoods are preferred when working with hazardous substances. Vertical flow
hoods are part of a family of equipment called biohazard cabinets or biological safety
cabinets. Three types of biohazard cabinets are available:
1. Class I cabinets have a HEPA filter on their exhaust outlet but not for inward
airflow. The protect personnel and the environment but do not prevent
contamination of compounded preparations. This class of hoods has no
application in compounding sterile preparations.
2. Class II cabinets have HEPA filtered inward air for protection of compounded
preparations and HEPA filtered exhaust air to protect personnel. They are
suitable for compounding sterile preparations. Class II cabinets are classified
according to how their exhaust air is vented.
a. Type A cabinet:
i. Maintains a minimum calculated average inflow air velocity of 75
ft/min through the work area access opening.
ii. Has HEPA filtered air from a common plenum (some air is
exhausted from the cabinet and some is supplied to the work area).
iii. May have air exhausted back into the controlled area.
iv. May have positive-pressure-contaminated ducts and plenums.
b. Type B cabinet exhausts some or all air outside the controlled area. These
cabinets are further classified as B1, B2, or B3:
i. B1 cabinet:
1. Maintains an average air velocity of 100 ft/min.
2. Has HEPA filtered down flow air composed largely of
uncontaminated, recirculated inflow air?
3. Exhausts most contaminated air to the atmosphere through
a dedicated duct and HEPA filter
4. Has all contaminated ducts and plenums under negative
pressure?
19
ii. B2 cabinet, sometimes called a total exhaust cabinet, differs from

B1 cabinet in that it:
1. Has all down flow air drawn through a HEPA filter from
the controlled area or outside, not recirculated from the
cabinet.
2. Exhausts all air to the atmosphere after HEPA filtration,
not to recirculation in the cabinet controlled area.
iii. B3 cabinet, sometimes referred to as a convertible cabinet:
1. Has HEPA filtered air that is a portion of the mixed down
flow and inflow air from a common exhaust plenum?
2. Exhausts all air to the atmosphere after HEPA filtration.
3. Can be converted from a Type B to a Type A cabinet if
desired.
3. Class III cabinets are totally enclosed, vented, and gastight units. Operations are
conducted through attached rubber gloves, and the cabinet is maintained under
negative pressure. These cabinets have limited applications in the preparation of
sterile products and are intended for the handling of extremely hazardous
substances
A biological safety cabinet functions by having air taken into the unit at the top, where it
passes through a prefilter to remove large contaminants. Air then passes through a HEPA
filter and is directed down toward the work surface, just as with a vertical laminar flow
hood. The filter forms the ceiling of the work area in the biological safety cabinet and
removes bacteria to provide ultraclean air. Unlike the mechanism in a vertical laminar
flow hood, however, as air approaches the work surface, it is pulled through vents at the
front, back, and sides of the unit. A major portion of the contaminated air is recirculated
back into the cabinet, and a minor portion is passed through a HEPA filter before being
exhausted into the room.
As just described, biological safety cabinets are of two basic types A Class II type A,
which is what we just described above, represents the minimum recommended
environment for preparing chemotherapy agents. Class II, type B biological safety
cabinets have greater intake flow velocities and are vented outside the building rather
than back into the room. This type of safety cabinet is preferred, but he need to vent the
filtered air outside can carry with it a substantial construction cost.
It is important that biological safety cabinets run continuously. If turned off for any
reason, such as for maintenance or changing the HEPA filter, the biological safety
cabinet must be thoroughly cleaned with a detergent, and the exhaust area must be
covered with impermeable plastic and sealed to prevent any contaminants from escaping
the unit.
20
Hood Selection.
Vertical laminar airflow hoods are the preferred choice. These cabinets prevent
cumulative exposure to potentially toxic medications, especially if the staff routinely
compound hazardous preparations for a long time.
When sterile preparations are compounded, aerosols can form and be blown toward the
operator using a horizontal hood. Long-term exposure to cytotoxic agents as well as
other drugs, especially antibiotics, is a great concern. Vertical airflow hoods minimize
such exposure.
The disadvantage of vertical airflow versus horizontal airflow hoods are expense and ease
of use. Class II hoods are more expensive than horizontal hoods and can be very costly
to install due to venting requirements. Furthermore, vertical airflow hoods generally are
more restrictive and may slow workflow.
Laminar Airflow Hood Basics
A laminar flow hood has three basic functions. The first is to provide clean air in the
working area. This is done by passing room air through a bacteria-retentive filter to
provide a continuous flow of clean air in the work area. Second, the constant flow of air
out of the laminar flow hood prevents room air from entering the work area. Last, the air
flowing out suspends and removes contaminants introduced in the work area by material
(such as IV bags, syringes, and drug packaging) or personnel. Thus, the laminar flow
hood provides an environment virtually free of airborne contaminants, in which
procedures can be safely performed.
Laminar flow hoods may be used in the pharmacy to perform the following procedures:
Preparations of IV admixtures
Preparations of ophthalmic solutions
Reconstitution of powdered drugs
Filling unit dose syringes
Preparation of miscellaneous sterile products.
Laminar flow hoods come in various sized and models. One model, called a console
model, sits on the floor. The other common model is called a bench or countertop model,
because it sits on top of the counter, and the space underneath it can be used for storage
space. Both the console and bench models are available with vertical rather than
horizontal airflow.
Laminar airflow hoods are usually kept running continuously. If the hood is turned off, it
is recommended to run for at least 30 minutes before using the work surface area in order
to replace the room air with clean, filtered air. Laminar flow hoods should be inspected
and certified every six months to assure that the HEPA filter is intact, unclogged, and has
no holes in it. The prefilters in the hoods should be changed monthly.
21
It is important for pharmacy technicians to keep their hands within the cleaned area of the
hood as much as possible, and to not touch their hair, face, or clothing. Only materials
essential for preparing the sterile products should be placed in the laminar airflow
workbench or barrier isolator.
Cleaning Laminar Airflow Hoods
Cleaning the laminar airflow hoods may be done with a non-shedding wipe or sponge
dampened with Water for Injection, with or without mild detergent. This should be
followed by:
Seventy percent isopropyl alcohol (or another appropriate disinfecting agent)

should be used to clean all interior working surfaces before each use.
A clean, lint-free cloth should be moved in a side-to-side motion, beginning at the
rear and moving toward the front of the LAH.
The walls of the LAH also must be cleaned from top to bottom with 70 percent
isopropyl alcohol.
This procedure should occur often throughout the compounding period and
whenever the work surface becomes dirty.
Because some materials require water to remove them, these materials may be
first cleaned off with water, followed by the alcohol or other disinfecting agent.
If the LAH has Plexiglas sides, they should be cleaned with warm, soapy water
instead of alcohol.
Spray bottles of alcohol or other disinfecting agents should never be used in the
LAH.
Once it is applied, alcohol should be allowed to air dry.
Needles
A needle consists of two parts: the shaft and the hub. The shaft is the long, slender stem
of the needle that is beveled (diagonal cut) at one end to form a point. The hollow bore
of the needle shaft is known as the lumen. At the other end of the needle is the hub, to
which a syringe can be attached (Figure 3-1).
22
Needle size is designated by length and gauge. The length of a needle is measured in
inches from the juncture of the hub and the shaft to the tip of the point. Needle lengths
range from inch to 3 inch or longer. The gauge of a needle, used to designate the
size of the lumen, ranges from 27, the finest, to 13, the largest. The finer the needle, the
higher the gauge number will be. In some disposable needles, the gauge is designated by
color of the hub. One factor in choosing the needle size is the thickness (viscosity) of the
injectable solution. A fine needle with a relatively small lumen may be acceptable for
most solutions, but a needle with a larger lumen and a smaller gauge number may be
needed for more viscous solutions. Another factor in selecting the proper needle is the
nature of the rubber closure to be penetrated. A fine needle with a smaller lumen may be
preferred for rubber closures that core easily, meaning that part of the rubber closure
gets carried into the drug solution when the needle penetrates the rubber closure.
Needles are sent from the manufacturer individually packaged in paper and plastic
overwraps. Sterility is guaranteed as long as the package remains intact. Therefore,
damaged packages should be discarded. The hub of the needles should not be touched
when removing the over-wrap.
23
A needle shaft usually is metal and is lubricated with a sterile silicone coating for smooth,
easy access into rubber closures. Therefore, needles should never be swabbed with
alcohol or touched. They should be handled by their protective covers only, and these
covers should be left in place until the needles or syringes are used. Used needles should
not be recapped, but rather discarded into a sharps container while still attached to the
syringe.
Filter needles are similar to other needles, except that they have a filter in the hub to catch
any particles from an ampule or vial and are used to vent small-volume vials.
Syringes
The two basic parts of a syringe are the barrel and the plunger (Figure 3-1). The barrel is
a tube that is open at one end, tapering into a hollow tip at the other end. The open end is
extended radically outward to form a rim, or flange, to prevent the barrel from slipping
through the fingers during manipulation.
The plunger is a piston-type rod with a slightly cone-shaped tip that passes inside the
barrel of the syringe. The other end of the plunger is shaped into a flat knob for easy
manipulation. The plunger must be able to move freely throughout the barrel, yet its
surface must be so close to the barrel that the fluid cannot pass between, even when under
considerable pressure.
The tip of the syringe provides the point of attachment for a needle. The tip may be
tapered to allow the needle hub to be slipped over it and held on by friction. When this
method is used, the needle is reasonably secure, but it may slip off if not properly
attached or is considerable pressure is used to inject the solution. Locking devices have
been developed to secure the needle more firmly on the tip of the syringe. These devices
incorporate a collar with a circular internal groove into which the needle hub is inserted.
A half-turn locks the needle in place. This method is especially valuable when pressure
is required.
Graduation lines on the barrel of the syringe indicate the volume of solution inside.
Accurate readings are more easily made if the color of the tip of the plunger is different
from that of the syringe itself. Syringes are disposable and have a capacity range of 1
60 ml. Graduation lines may be in milliliter, depending on the capacity of the syringe;
for example, the larger the capacity of the syringe, the larger is the interval between
graduation lines. Special purpose syringes, such as insulin syringes, have graduation
lines in both milliliters and insulin units to reflect their intended use.
In the selection of an appropriate syringe, as a rule the capacity of the syringe should be
the next size larger than the volume to be measured. For example, a 3 ml syringe should
be selected to measure a 2.3 ml dose, or a 5 ml syringe to measure a 3.8 ml dose. In this
way, the graduation marks on the syringe will be in the smallest possible increments for
the dose measured. Syringes should not be filled more than three-quarters of capacity.
24
Sterile, disposable syringes are discarded after one use and have the same advantages as
disposable needles. Although syringes today are made of plastic because it cost less,
glass syringes can still be bought for drugs that are incompatible with plastic. Syringes
and needles need to be disposed of in a sharp container. Do not recap needles after they
have been used.
Some common doses of frequently used or emergency drugs come in prefilled syringes.
Prefilled syringes eliminate the need to measure doses, thus saving time. Prefilled
syringes are commonly seen in emergency carts or are used in emergency rooms when it
is critical to get the medication to the patient as quickly as possible.
Most prefilled syringes are supplied in a syringe that does not have a plunger. This is to
prevent the drug from accidentally squirting out if pressure were applied to the plunger
when being stored or transferred.
Vials
Injectable medications usually are supplied in vials or ampuls, each requiring different
techniques for withdrawal of the medication. A vial is a plastic or glass container with a
rubber closure secured to its top by a metal ring. Multidose vials contain preservatives
that allow their contents to be used after the rubber stopper is punctured. This stopper
usually is protected by a flip-top cap or metal cover, but most caps do not guarantee
sterility of the rubber closure. Therefore, all vials should be swabbed with 70% isopropyl
alcohol before needle entry and left to dry. The correct technique is several firm strokes
in the same direction over the rubber closure, using a clean, unused portion of a swab on
each pass. The swabbing is effective in two ways:
The alcohol acts as a disinfecting agent.

The physical act of swabbing in one direction remove particles from the vial
diaphragm.
Bottles or trays of isopropyl alcohol should not be used. Because alcohol may harbor
resistant spores, repeated use of non-sterile tray or bottle could promote this problem.
Individually packaged swabs are sterile from the manufacturer.
When vials are pierced with needles, cores or fragments of the rubber closure can form.
To prevent this problem, the needle should be inserted so that the rubber closure is
penetrated at the same point with both the tip and heel of the bevel. This noncoring
technique is accomplished by first piercing the rubber closure with the bevel tip and then
applying lateral (away from the bevel) and downward pressure to insert the needle.
Vials are closed-system containers, since air or fluid cannot pass freely in or out of them.
Therefore, the volume of fluid to be removed from a vial should be replaced with an
equal volume of air to avoid creating a vacuum. But this technique should not be used
with drugs that produce gas when they are reconstituted (e.g., ceftazidime).
25
If the drug within a vial is in a powered form it must be reconstituted first. The desired
volume of the diluent (e.g., sterile water for injection) is injected into the vial. As the
diluent is added, an equal volume of air must be removed to prevent a positive pressure
from developing inside the vial. This procedure may be accomplished by allowing air to
flow into the syringes before removing the needle from the vial. Although most drugs
dissolve rapidly when shaken, a technician must be sure that a drug is completely
dissolved before proceeding.
Ampuls
Ampuls are composed entirely of glass. Once an ampul is broken, it becomes an opensystem, single-use container. Since air or fluid may now pass freely in and out of them,
the volume of fluid removed does not have to be replaced with air.
Before an ampul is opened, any solution visible in the top portion (head) should be
moved to the bottom (body) by one of the following methods:
Swirling the ampul in an upright position.

Tapping the head with ones finger
Inverting the ampul and then quickly swinging it into an upright position.
To open an ampul properly, its neck should be cleansed with an alcohol swab and the
swab should be left in place. This swab can prevent accidental cuts to the fingers as well
as spraying of glass particles and aerosolized drug. The head of the ampul should be held
between the thumb and index finger of one hand, and the body should be held with the
thumb and index finger of the other hand. Pressure should be exerted on both thumbs,
pushing away from oneself in a quick motion to snap the ampul open at the neck.
Ampuls should not be opened toward the HEPA filter of the laminar airflow workbench
or toward other sterile products within the workbench. Extreme pressure may result in
crushing the head between the thumb and index finger. Therefore, if the ampul does not
open easily, it should be rotated so that pressure on the neck is at a different angle.
To with draw medication from an ampul, it should be tilted and the bevel of the needle
placed in the corner space (or shoulder) near the opening. Surface tension should keep
the solution from spilling out of the tilted ampul. The syringe plunger is then pulled back
to withdraw the solution.
The use of a filter needle eliminates glass or paint chips that may have fallen into a
solution from being drawn up into the syringe. Sometimes, a medication (e.g., a
suspension) may need to be withdrawn from an ampul with a regular needle; a filter
needle should then be used to push the drug out of the syringe. In all cases, the same filer
needle should not be used for both withdrawing and injecting, since it will mollify the
filtering effort.
26
IV Bags
Plastic bags are used for diluting a solution and are the most common way of
administering intravenous medications to patients. Plastic bags are available in many
different sizes, with 50, 100, 250, 500, and 1000 ml being the most common. Special
bags for compounding parenteral nutrition are available in 2,000 ml and 3,000 ml sizes.
Some IV bags are made of PVC (polyvinyl chloride). More expensive than plastic bags,
these bags are used for specific drugs (like Taxol) that can adhere to the plastic of the
non-PVC IV bags.
At the top of the bag is a flat plastic extension with a hole to allow it to be hung on an
administration pole. At the other end of the bag are two ports of about the same length.
The administration set port has a blue plastic cover that serves to maintain the sterility of
the port. The cover is easily removed by pulling on it. Once it is pulled off, the sterile
port of the administration set is exposed. Solution will not drip from the plastic bad at
this point because a plastic diaphragm about inch inside the port seals in the liquid.
The spike of the administration set is inserted into the port, puncturing the inner
diaphragm to allow the solution to flow from the flexible plastic bag into the
administration set. When the solution has filled the administration set (this process is
called priming the set), make sure to clamp the administration set so that the solution
does not leak out. Once the inner diaphragm is punctured, it is not resealable.
The other port is the medication port. It is covered by a protective rubber tip.
Medication is added to the solution through the medication port by means of a needle and
syringe. The rubber tip is self-sealing, thus preventing solution from leaking when the
needle punctures the tip. Approximately inch inside this port is a plastic diaphragm
that must be punctured for solution to enter the bag. The inner diaphragm is not selfsealing when punctured by a needle, so the rubber tip must stay attached to the bag.
Graduation marks to indicate the volume of solution infused are located on both sides of
the front of some plastic bags at 25-100 ml intervals, depending on their capacity.
When you place a label on a plastic bag, it does not matter which side of the bag you
place the label; however, many institutions place the label on the printed side of the bag,
beneath the solution name, and offset slightly to one side so that the graduation marks
near the side can still be read. This procedure has the advantage of providing a
convenient cross-check between the actual solution and the name appearing on the
admixture label.
Some IV solutions, such as 5 percent dextrose injection and 0.9 percent sodium chloride
injection, are available in minibags, or piggyback bags. These bags typically hold 50 ml
or 100 ml of solution and are used to administer drugs intermittently rather than
continuously.
The plastic bag system is completely closed to air. It does not depend on air to displace
the solution as it leaves the bag. The bag collapse as the solution is administered, so a
vacuum is not created inside.
27
IV. Aseptic Technique

Sterility
Sterility is the freedom from bacteria and other microorganisms. Solutions to be injected
must be sterile. A product is either sterile or not sterile; products cannot be partially
sterile. Sterility cannot be visibly seen, but proper aseptic technique can maintain the
sterility of solutions, drugs, and supplies during preparation.
While the importance of sterility was first recognized in the late 1800s, the concept of
aseptic technique was not described until years later.14 The need to sterilize solutions and
equipment became accepted in the 1920s and 1930s.15 Moreover, the development of
sterile and pyrogens-free products and their applications continues today.
In the late 1960s improperly manufactured and compounded IV solutions caused a rash
of complications in patients.16 Following these incidents, the National Coordinating
Committee on Large Volume Parenterals (NCLVP) published recommendations for
techniques to compounding sterile preparations for pharmacist and other professionals.
A training manual for IV admixture personnel, largely intended for pharmacy technicians
who prepare sterile products, was first published in 1972. This manual was revised in
1990.
The American Society of Health-System Pharmacists (ASHP) published a videotape and
study guide on aseptic technique. This combination product was the first comprehensive
guide to aseptic technique with practical application to many pharmacy settings. ASHP
and the United States Pharmacopeial Convention (USP) publish guidelines regarding
aseptic technique and further established practice standards for compounding sterile
preparations. ASHPs Manual for Pharmacy Technicians, third edition also includes a
chapter on technician training as it relates to aseptic technique and compounding sterile
preparations.
Aseptic Technique: Overview
Aseptic technique is carrying out a procedure under controlled conditions in a manner
that minimizes the chance of contamination. Contamination can be caused by the
following factors:
Environment controlling the air where the compounding is being performed.

Equipment all objects that come in contact with the drug(s) must be sterile.
Personnel touch contamination is the most frequent cause of contamination.
14
Griffenhagan GB. The history of parenteral medication. BullParenter Drug Assoc. 1962; 16:129.
Masson AH. The early days of intravenous salin. PharmJ. 1976; 217:571-80.
16
Maki DG, Goldmann DA, Rhame FS. Infection control in intravenous therapy. Ann Intern Med.
1973:79:867-87.
15
28
The preparation of sterile drug compounds requires the utmost diligence to ensure final
product integrity and sterility. Sterile products must be prepared with aseptic technique
in a class 100 environment containing no more that 100 airborne particles of a size 0.5
micron and larger, per cubic foot of air. As discussed earlier, such an environment exist
inside a certified horizontal or vertical laminar flow hood, a class 100 clean room, and a
barrier isolator. A barrier isolator is a closed system made up of four solid walls, an airhandling system, and a transfer and interaction compartment.
Aseptic technique refers to the procedures used during preparation that maintains the
sterility of pharmaceutical dosage forms. Sterilization is an essential concept in the
preparation of sterile pharmaceutical products. Its aim is to provide a product that is safe
and that eliminates the possibility of introducing infection.
Sterilization is a process used to destroy or eliminate viable microorganisms that may be
present in or on a particular product or package. The process requires an overall
understanding and control of all parts of the preparation for use of a particular product.
Aseptic technique describes the methods used to manipulate sterile products so that they
remain sterile. Technique is a separate element in compounding of sterile preparations,
independent from equipment and the environment. Proper technique does not eliminate
the need for good equipment and a proper environment. Conversely, good equipment
and an ideal environment do not change the need for a good technique.
Equipment and Environment
The laminar airflow hood workbench (LAFW) is considered critical equipment for good
aseptic technique. Issues related to handling and compounding of cytotoxic agents and
using a biological safety cabinet are not addressed here, because they were discussed in a
previous section.
The critical principle in the use of LAFWs is that nothing should interrupt the airflow
between the high-efficiency particulate air (HEPA) filter and the sterile object. This
aseptic compounding space is referred to as the critical area and any foreign object can
increase turbulence within this area. Contaminants from the foreign object may be blown
or carried onto the sterile injection port, needle, or syringe. Large materials placed within
the LAFW also can disturb the patterned flow of air from the HEPA filter. This zone of
turbulence created behind an object could extend outside the workbench, pulling or
allowing contaminated room air into the aseptic environment.
When laminar airflow is accessible to all sides of an object, the zone of turbulence
extends approximately three times the diameter of that object. When airflow is not
accessible on all sides (e.g., adjacent to a vertical wall), a zone of turbulence may extend
six times the diameter of an object. For these reasons, objects should be at least 6 inches
from the sides and front edge of the workbench, without blocking air vents and without
obstructing airflow. Hands also should not block airflow.
29
The following are general principles for proper operation of LAFWs:

1. All aseptic manipulations should be performed at least 6 inches within the LAFW.
This distance prevents reflected contamination from the technicians body and
back-wash contamination from turbulent air patterns developing at the LAFWroom air interface.
2. A LAFW should operate continuously. If the LAFW is turned off, it should not
be used for a specified time when reactivated, depending on the manufacturers
recommendations (e.g., 30 minutes). This downtime allows all room air to be
purged from the critical area.
3. Before use, all interior working surfaces of the LAFW should be cleaned with
70% isopropyl alcohol or another disinfecting agent and a clean, lint-free nonshedding cloth. Cleaning should be performed from back to front so that
contaminants are moved away from the HEPA filter. Throughout the
compounding period, the LAFW should be cleaned often. Some materials are not
soluble in alcohol and may initially require water for removal. To avoid damage,
Plexiglas sides should be cleaned with warm, soapy water rather than alcohol.
4. Nothing should touch the HEPA filter, including cleaning solution, aspirate from
syringes, and glass from ampuls. Ampuls should not be broken directly toward
the filter.
5. A LAFW should be positioned away from excess traffic, doors, air vents, fans,
and air currents capable of introducing contaminants.
6. Hand and wrist jewelry should not be worn; jewelry may introduce bacteria or
particles.
7. Actions such as talking and coughing should be directed away from the critical
area, and any unnecessary motion should be avoided to minimize airflow
turbulence.
8. Only objects that are essential to compounding sterile preparations should be
placed in the LAFW, no paper, pens, labels, or trays.
9. LAFWs should be tested and certified by qualified personnel every 6 months,
whenever the LAFW is moved, and if filter damage is suspected. Tests can
certify airflow velocity and HEPA filter integrity.
10. Food and drink should not be permitted within the aseptic preparation area
(controlled or critical area).
30
Although the LAFW provides a sterile environment, the strict aseptic technique must be
used to ensure the sterility of the final preparation. The two most critical aspects of
aseptic technique are proper hand washing and use and manipulation of syringes, needles,
vials, and ampuls.
Hand Washing
Touch is the most common means of contaminating a pharmacy-compounded sterile
preparation. Since the fingers harbor bacterial contaminants, hands should be washed
properly.
For nearly 200 years, cleansing hands with an antiseptic agent has been recommended to
prevent transmitting contagious diseases to patients.
Hands must be washed properly, by using the correct technique. Proper hand washing
depends on running water, a cleansing agent, and friction. The hands, fingernails, wrists,
and forearms should be scrubbed under running water, with the fingertips pointing
downward. Soap and friction are applied to the hands and wrist.
Proper hand washing includes the following steps:
1.
2.
3.
4.
5.
6.
7.
8.
9.
Remove all wrings and watches.

Stand close to, but not touching, the sink.
Turn on the faucet using a foot pedal or a dry sterile towel. Discard the towel.
Wet hand, wrists, and forearms under running warm water, and apply liquid
antibacterial soap.
For 15 to 30 seconds, scrub the palm of one hand with the fingers of the other
hand, then repeat for the opposite hand.
Use a brush and scrub the fingernails and backs and palms of the hands, and then
scrub the wrists and forearms.
Hold the hands in a downward position and rinse well.
Dry the hands and then the wrists gently with a sterile towel.
Use a dry, sterile towel to turn off the faucet if it is not operated by a foot pedal.
Hand-washing agents should be selected based on their ability to kill microorganisms on

the hands at the time of washing and also to provide a residual effect. Isopropyl and ethyl
alcohol hand rinses, gels, or foams, or a solution of 4% chlorhexidine gluconate are the
best agents for reducing resident flora and transient microorganisms.
Results vary with isopropyl alcohol products for initial reduction of microorganisms, but
these products clearly have little residual effect. Since most alcohol products are
solutions, gels, or foams, they serve as hand disinfectants rather than hand-washing
agents. Therefore, hand washing with soap before application of these agents sometimes
is recommended. However, this additional step might lower compliance with procedures.
31
When decontaminating hands with an alcohol-based hand rub, apply product to palm of
one hand and rub hands together; covering all surfaces of hands, and fingers, until hands
are dry. Follow the manufacturers recommendations regarding the volume of product to
use. Multiple-use cloth towels of the hanging or roll type are not recommended for use in
health-care settings.
Hand washing is sometimes incorrectly omitted when gloves are worn, the assumption
being that they provide enough hand protection. In fact, microorganisms multiply rapidly
inside warm moist gloves and then can leak through them. The Center for Disease
Control (CDC) has stated that gloving does not replace hand washing and that hand
washing is imperative after gloves are removed.17
Clean Room
A clean room is an area that is specially constructed and maintained to reduce the
probability of environmental contamination of sterile products during the manufacturing
process. Clean rooms must meet the high standards of purity and cleanliness for
parenteral compounding products, and must follow USP 797, which is a stringent set of
rules and regulations regarding aseptic preparations.
USP 797 requires that the surfaces of all floors, wall, ceilings, cabinets, shelving, and
work surfaces in the buffer room should be soft and smooth. These surfaces must also be
free from crevices or cracks, making them easy to clean and sanitize.
Because air is one of the greatest potential sources of contaminants in clean rooms,
special attention must be given to air being drawn into clean rooms by the following
systems:
Heating
Ventilation
Air conditioning
Personnel entering the aseptic area should enter only through an airlock. They should be
attired in sterile coveralls with sterile hats, masks, goggles, and foot covers. Traffic flow
into the room should be minimized and in-and-out movement rigidly restricted during a
filling procedure. Clean rooms sometimes have an anteroom that is used for non-aseptic
activities related to the clean room operation such as:
Gowning
Handling stock
Order processing
17
Update: universal precautions for prevention of transmission of human immunodeficiency virus, hepatitis
B virus, and other bloodborne pathogens in healthcare settings. MMWR. 1988:37 (June 24): 377-83, 387-8.
32

V. Procedures for Compounding of Solutions
A sterile product contains no living microorganisms. The need for sterility is based on
the fact that through injection, the major body defense mechanisms are bypassed. In the
hospital, a majority of patients will receive a medication that is administered by injection.
Examples of ophthalmic preparations that must be sterile include ointments, solutions,
and suspensions. Sometimes pharmacy technicians must compound two solutions that
are not commercially available. An example is the compounding of two materials that
are both liquid in nature.
Procedure for Compounding Solutions
The procedure for sterile compounding of solutions must be performed in the clean air
space by using proper aseptic technique, as follows:
Prepare all materials needed for the procedures.

Swab the rubber tops of vials with alcohol and wait for them to dry.
Pull the plunger back on the syringe slightly, and then pull the amount needed to
by drawn up.
Insert the needle through the stopper.
Push the air from the syringe into the vial.
Withdraw the desired amount of medication.
Withdraw the needle.
Add the medication into the IV bag.
Gently shake the bag of solution.
Label the product of compounded solution.
Store the product in the refrigerator.
Sterile preparations may be compounded in various final containers, including flexible

plastic bags, glass bottles, semi-rigid plastic containers, and syringes, or as the drug vial
itself. Flexible plastic bags made of polyvinyl chloride (PVC) or polyolefin are easy to
store compared to glass bottles, less likely to break, and do not need to be vented.
PVC bags are available in several sizes and solution types. These bags are supplied in
plastic over-wraps, which limit fluid loss. Once this over-wrap is removed, the remaining
solution should be used as soon as possible. The injection port of a PVC bag, covered by
a protective rubber tip, should be positioned toward the HEPA filter when an IV
admixture is prepared. This positioning minimizes air turbulence in the critical area.
Before compounding, all material should be assembled. Vials, ampuls, and IV solution
containers should be inspected for cloudiness, particulate matter, cracks or punctures,
expiration dates, and any indications of defects. Only necessary materials should be
placed with in the LAFW.
Next, all injection surfaces should be disinfected. Drug fluid should be withdrawn from
its container in the amount needed, using the syringe size just larger than the volume to
33
be injected. To obtain an accurate measurement, air bubbles should be removed by the

following method:
1. Pulling back slightly on the plunger to remove any fluid trapped in the needle.
2. Tapping the syringe.
3. Depressing the plunger.
The instillation of drug into a PVC bag requires insertion of a needle into the alcoholswabbed injection port and injection of the appropriate volume of fluid. The injection
port has two diaphragms that must be pierced:
Outside latex tip.

Plastic diaphragm about inch inside the injection port.
To ensure fluid transfer into the IV bag, a needle longer than inch should be used.
Adding medication to a glass infusion container begins with removal of the protective
cap from the IV bottle. A drug additive then is injected through the alcohol-swabbed
rubber stopper or latex diaphragm. Needles should be inserted through rubber stoppers
using the non-coring technique previously described for vials. Following admixture, a
protective seal is placed over the stopper of a glass container before it is removed from
the laminar-airflow workbench.
If the final sterile preparation is in a syringe, the needle used in compounding should be
removed and discarded. The syringe should then be capped with a sterile tip. A small
volume of air or overfill may be left in the syringe for priming the needle or tubing before
administering the dose. The syringe should be placed in a plastic bag or other container
for transport, which minimizes the potential for plunger depression and/or leakage.
Once the sterile preparation is compounded, it should be properly labeled and inspected
for cores and particulates. All drug and IV solution containers should be checked by a
pharmacist to verify that the technician added the proper amount of the correct drug to
the correct IV solution and the correct label affixed to the compounded preparation.
Compatibility
Not all drugs are compatible with each other. The incompatibility may be between two
drugs or between a drug and an IV solution. The possibility of an unexpected or
undesirable combination is relatively low compared with the number of IV admixtures
prepared, but it is always possible. An incompatibility can lead to a patient not receiving
the full therapeutic dose of a medication or, even worse, can lead to an adverse reaction.
Some incompatibilities, such as a color change or hazy appearance, can be seen.
Precipitate can form in the solution, or an evolution of a gas may even be smelled. Be
aware that sometimes when drugs are combined and a visible change occurs, it could be
expected and harmless. Reading the package insert or checking with the pharmacist can
confirm the reason for this change in appearance. Other incompatibilities cannot be
34
visually recognized. If two drugs are mixed that are incompatible with each other, one
drug can cause the degradation of the other drug. Many factors can affect the
compatibility and stability of drugs in IV admixtures. The following list describes each
of these factors:
pH pH is one of the most common causes of incompatibilities. Combining two

drugs that require two different pH values for the final solution can cause one or
both drugs to either degrade or precipitate.
Light Some drugs will start to break down and lose their therapeutic effect if
exposed to light.
Dilution the concentration of a drug in solution may be a factor in its

compatibility with other drugs. A problem can be avoided by assuring that the
drug in question is properly diluted before it is combined with the other drug.
Chemical composition the chemical complexity of one drug can cause a reduced
therapeutic effect of the other drug, because when the two drugs combine, their
new chemical combination may initiate adverse events.
Time Most drugs start to degrade in a short time after being added to an IV
solution.
Solutions Some drugs require a specific solution or diluent to be used for

reconstitution and further dilution. Choosing the wrong solution can cause the
drug to be broken down more quickly or can cause precipitate to form. Some
drugs are packaged with a specific diluent for reconstitution.
Temperature Heat increases the rate of most chemical reactions, and since the
degradation of a drug in solution can be considered a chemical reaction, care must
be taken to keep admixtures at a stable temperature. Some drugs can remain more
stable refrigerated than if they were kept at room temperature. Some drugs,
however, should never be refrigerated because a precipitate can form. Not many
experts recommend freezing drugs after reconstitution, and sometimes freezing
actually reduces the stability of the drug.
Buffer capacity this is the ability of a solution to resist change in pH when either
an acidic or alkaline substance is added to the solution. Many drugs contain
buffers to increase their stability. IV solutions in general do not have high buffer
capacities. So, when a drug with a high buffer capacity is added, the resulting
solution will have a pH closest to the drug added.
Order of Mixing the order in which drugs are added to the solution may be a
factor in compatibility. Drugs that are concentrated and combined may react to
form precipitate, whereas both drugs in diluted solutions may be combined
acceptably. This is very important when mixing parenteral nutrition solutions.
35
Electrolytes are commonly prescribed with phosphates, and this causes a mixing
problem when mixing parenteral solutions if it is not done correctly. To avoid the
problem, it is important to mix the solution well after each addition is made and
then to add the electrolytes last after the phosphate has been diluted.
Plastic some drugs are incompatible with the plastic container that the solution
will be placed in. Polyvinyl chloride (PVC) plastic can leach certain properties of
the plastic out of the bad, or the drug may adhere to the bag. It is recommended
that one use non-PVC container for these specific drugs.
Filters Filters represent a possible problem in effectively administering a drug to

a patient. Filters can cause a reduction in concentration of the drug to be
administered.
To minimize incompatibilities, the following guidelines need to be followed whenever

possible:
1. Use solutions promptly after preparation in order to ensure administration of the
most stable product; drugs tend to degrade in a relatively short time. If a newly
made admixture is not immediately used, it should be placed in the refrigerator.
2. Minimize the number of drugs added to a solution. As the number of drugs added
increases, the chance of an incompatibility rises. It becomes increasingly difficult
to find information on compatibilities when more than two drugs are added to a
solution.
3. Check incompatibility resources to verify which drugs have a very high or very
low pH. Since most drugs are acidic, their combination with a drug having a very
high pH is more likely to result in an incompatibility.
The most often used resources for information on incompatibilities are the
manufacturers drug package inserts. The package inserts have a wealth of information
about the drug. The package insert is developed by the manufacturer and approved by
the FDA (Food & Drug Administration) when the drug is marketed. The package insert
generally is not as great a reference for incompatibilities specifically; however, there are
other excellent resources out there, like The American Journal of Health-System
Pharmacy frequently has detailed research articles on intravenous incompatibilities.
Some very useful reference books are the Handbook of Injectable Drugs and the Facts
and Comparisons Book. Many pharmacy departments maintain a file that categorizes
drugs to make looking up drug information quicker and easier. Some pharmacy
computer systems screen IV admixture incompatibilities as well as drug interactions,
alerting the pharmacist or pharmacy technician to these issues when the order is entered,
before it is prepared.
36

VI. Labeling
A properly compounded sterile preparation, must be labeled accurately and completely to

facilitate appropriate and safe administration to the patient. Checking the accuracy of the
compounded sterile preparations label independently against the original physicians
order/prescription and the ingredients used to compound the preparation is an integral
part of the pharmacists verification process prior to release of the preparation. In
addition, the sterile preparations primary and auxiliary labels serve as communication
tools regarding proper handling, storage, administration, and drug information for the
person administering the drug to the correct patient. Therefore, the terminology used on
the label should be descriptive but still appropriate to the knowledge of the user with the
use of abbreviations minimized. All labels should be legible and affixed to the final
container in a manner enabling them to be read both before and while the sterile
preparation is being administered. If a container is to be hung, each label must be
positioned so that it is right side up during administration. Light-resistant bags, for
photosensitive drugs, and other overwraps should not limit the visibility of the label.
Small containers may require unique methods of affixing the label. For medium-sized
syringes, labels often are flagged so that syringe markings are not covered or
obstructed. Labels are often flagged for compounded sterile preparations dispensed in
small vials and ophthalmic bottles. Very small syringes can be sealed in a larger bag or
overwrap, which is then labeled. If the syringe might be removed from the bag some
time before administration, a second, smaller label on the syringe should give key
information (e.g., drug name, concentration, beyond-use date, and route). Based on the
sterilization method, e.g., steam; final labeling with all required labeling components may
need to occur post-sterilization.
The exact information on a label varies based on the preparation type and the patients
location/setting, not the ASHP or USP compounded sterile preparation risk-levels.
Effective 2004, there are official USP required labeling elements for all compounded
sterile preparations regardless of where the patient is receiving the preparation.18 General
label content is similar, but slight variations exist in addition to the USP standard for
patient specific labeling in institutional and home care settings as well as for compounded
sterile batch preparations. This chapter will review general labeling guidelines, the USP
labeling requirements for sterile preparations, both required and optional patient specific
labeling elements as specified by ASHP and JCAHO, batch labeling elements, and
additional labeling strategies that can be utilized to help prevent medication errors and
facilitate proper disposal of returned preparations to ensure compliance with the
Healthcare Insurance Portability and Accountability Act (HIPPA) privacy regulations.
18
Pharmaceutical compounding Sterile preparations. In: United States pharmacopeia, 27th rev./national
formulary, 22nd ed. Rockville, MD: United States Pharmacopeial Convention.
37
General Labeling Guidelines

In order to ensure proper labeling, the following guidelines should be followed:
Drug labeling is required if the compounded sterile preparation is not

administered immediately or if it is administered by someone other than the
person who prepared the medication.
The label conforms to all applicable federal, state and local laws and regulations.
Medication labels are typed or electronically printed in a standardized format to

ensure accurate and complete labeling. The label is legible, easily read, and free
from erasures and strikeovers.
The appropriate primary and auxiliary labels are firmly affixed to the container.
The metric system of measures should be used instead of the apothecary system.
Numbers, letters, coined names, unofficial synonyms, and prohibited

abbreviations are not used to identify medications with the exception of approved
letter or number codes for investigational drugs.
All medications with illegible or worn labels are properly and safely destroyed.
A uniform, systematic labeling method is used. One order or drug preparation

batch is filled and labeled at a time.
During the hours the pharmacy is open, dilutions and labeling are done in a
pharmacy. Within the pharmacy, only a pharmacist or authorized pharmacy
technician under the direction and supervision of a pharmacist, may label and
dispense medications, make labeling changes, or transfer medications to different
containers.
UPS Labeling Requirements for Compounded Sterile Preparations

With the introduction of the new United States Pharmacopeias (USP) Chapter <797>,
there exists a minimum labeling standard for compounded sterile preparations that
applies to all health care settings, not just health care institutions and pharmacies. The
parts of a label are described below; the numbers in parenthesis correspond to
information on the label.
Names and amounts or concentrations of ingredients
The name of each drug, preferably generic, should be clearly shown. This includes the
names of all drug products or ingredients added or used to prepare the finished
preparation, including admixture solutions and their corresponding volumes. The trade
38
drug name or commonly known name of the preparation can be included if it can reduce
the potential for error. Although the amount or volume of admixture solution, e.g.
dextrose or sodium chloride, usually is unimportant in the patients therapy, it may be a
consideration in certain clinical settings. The admixture solution itself; however,
definitely affects the compounded sterile preparations stability and beyond-use dating.
Total volume of the preparation
Total volume is usually expressed in the metric system, e.g., milliliters (mls) or liters.
For IV piggybacks and continuous infusions, this measurement allows tracking the
patients total fluid intake. If the volume of the admixture solution is not significantly
different from the total volume, these measurements are used interchangeably (e.g.,
antibiotic solutions). For larger volume solutions with multiple additives, the actual or
calculated total volume should be used (e.g., TPN solutions). For syringes and vials that
are overfilled, both scribed medication dose should be clearly shown on the label.
Beyond-use date
This date is the last date that the sterile preparation can be used by the patient and should
be consistent within each health care setting. Beyond-use dating should be based on
known stability information and sterility considerations. The specific beyond-use date of
a preparation should be based on published data, appropriate testing, or USP-NF
standards.
Appropriate route(s) of administration
Even though the route of administration may be implied by the dosage form (e.g., IV bag
implies IV or intravenous administration unless labeled otherwise), the appropriate
route(s) of administration should be placed on the preparations label. Especially when a
container is used outside of the normal pattern or a dosage form has multiple uses, the
route must be clearly stated to prevent medication errors. Often, drugs can be given only
be certain routs or the amount/concentration is route specific and, therefore, may be
dangerous otherwise.
Syringes should be clearly labeled with the intended route of administration (e.g., IV
push, pump or gravity, epidural, or Intrathecal, intravitreal, or intramuscular). In some
cases, the ramifications of giving a particular drug or dose by an unintended route can be
fatal. Patient-controlled analgesia (PCA) containers also should be clearly marked since
they may be the same for IV and epidural PCA, but the concentration of drug differs.
Storage conditions
Storage instructions can be put on the primary label or added as an auxiliary label.
Preparations must be stored in accord with the condition stated on the label to ensure the
preparations sterility and stability. This can include, but is not limited to, whether the
preparation should be refrigerated, kept at room temperature, protected from light, or not
39
shaken. If the sterile preparation requires refrigeration, it should be separated from food
to avoid contaminating the outside of the container.
Other information for safe use
Other information, including cautionary statements, for the safe use of the preparation
can be put on the primary label or added as auxiliary labels. This information should
include the initials of the responsible pharmacist who prepared or checked the preparation
and complete directions for the proper clinical administration of the compounded sterile
preparation, including device specific settings and instructions. In addition, hazardous
drugs should have appropriate precautionary labels to facilitate safe handling, use, and
disposal.
40
VII. Storage and Handling of Sterile Preparations

Monitoring the storage conditions in the pharmacy is necessary to ensure that sterile
products retain their respective quality attributes. Controlled-temperature storage areas
such as refrigerators and freezers should be monitored at least once daily with results
documented on a temperature log.
This section covers pharmacys responsibility for sterile commercial products and
compounded preparations beginning when products are first received and continuing
through compounding and waste disposal. To ensure both preparation quality and public
safety, correct storage and handling procedures are necessary every step of the way.
Sterile Components
Components are comprised of active and inactive ingredients, intermediate containers
(e.g., a syringe used to transfer a drug from one container to another), final containers and
closures. A procedure should specify the visual inspection of commercially available
drug products, sterile ready-to-use containers, and devices (e.g., syringes and needles)
upon receipt in the pharmacy. All items must be free from defects, within the
manufacturers expiration dating, and suitable for their intended use.
USP Storage Conditions
Intravenous solutions, sterile commercial product, and sterile supplies should be stored
according to manufacturer labeling or USP product monographs to preserve stability of
ingredients. Most sterile products are aqueous solutions for which hydrolysis is the most
common chemical degradation reaction. In general, the rate of a chemical reaction
increases exponentially for each 10 C increase in temperature. Thus, storage of a betalactam antibiotic solution for one day at controlled room temperature will have an
equivalent hydrolytic effect of approximately 3 to 5 days in cold temperatures. Cold
temperatures may cause harm as well, for example refrigeration may cause harm as well,
for example refrigeration may cause precipitates and freezing may break an emulsion or
denature proteins.
Recommended storage conditions are usually stated on a products label and may include
a specified temperature range or a designated place (e.g., refrigerate). Supplemental
instruction (e.g., protect from light) should also be followed carefully. If a preparation
must be protected from light and is in a clear or translucent container enclosed in an
opaque outer covering, this covering should not be removed until the contents are to be
used.
In the absence of specific instructions, a sterile product should be stored at controlled
room temperature away from excessive or variable heat, cold, and light, e.g., away from
heating pipes and fluorescent lights.
41
Clarifying Controlled Room Temperature

Since controlled room temperature may range from 15 C to 30 C, such storage may not
be adequate for certain temperature-sensitive drugs. Clinically important changes can
result from only a 5 C variation in room temperature over the shelf life of a preparation.
Alterations in temperature-related drug stability could potentially compromise an
interpretation and assignment of beyond-use dates to compound preparations. Therefore,
USP has further defined controlled room temperature:
Controlled room temperatureencompasses the usualworking environment of
20 C to 25 C (68 to 77 F)that results in a mean kinetic temperature
calculated to be not more than 25 degrees; and that allows for excursions between
15 and 30 degrees C (59 and 86 F)in pharmacies, hospitals, and warehouses.
Monitoring Storage Conditions
To ensure that the potency of a sterile commercial product is retained through its
expiration date, pharmacy personnel must monitor drug storage areas. Controlled
temperature areas like refrigerators, freezers, and incubators should be monitored at least
once daily and the results should be documented on a temperature log. A continuous
temperature recording device or a thermometer with adequate accuracy and sensitivity
may be used if properly calibrated at reasonable intervals.
On each day, pharmacy personnel should verify that the recording device is working and
that temperatures are within the desired range. The temperature-detecting mechanism
should be carefully placed so that it accurately reflects the units temperature. The
pharmacy personnel must also monitor conditions that cause temperature fluctuations
such as frequent or extended opening of refrigerator doors.
Outside the Pharmacy
While compounded sterile preparations are within the confines of a clean-room, storage
and other handling conditions can be largely controlled. Since sterile preparations must
be transported for use in various patient care settings, their handling outside the pharmacy
also must be considered. Efforts must focus on the acceptable focus on the acceptability
of the sterile preparation for patient use (including stability of ingredients and sterility)
and also on the reduction of waste and preparation costs. Key factors to consider include
the transfer of sterile preparation form the sterile compounding area, storage conditions
during transport and in the storage conditions during transport and in the patient care
setting, and methods for return, recycling, and disposal. USP chapter <797> states that
pharmacy is responsible for ensuring that compounded sterile preparations maintain their
quality until administration to the patient. All personnel (including couriers and other
non-pharmacy staff) who package, handle, transport, and store compounded sterile
preparations outside the pharmacy must be appropriately trained so that this expectation
is met.
42
Quality Control
Quality control is the day-to-day assessment of all operations from the receipt of raw
materials to the distribution of the finished product.
Quality assurance is an oversight function, involving the adjusting of quality-control
procedures and systems, with suggestions for changes as needed.
Each pharmacy should have written procedures covering the following:
Handling and storage

Preparing admixtures
Labeling
Transportation of IV fluids to the floors
Personnel involved in the preparation of IV admixtures should be trained and monitored

on a regular basis. For quality control, documentation is essential and should include:
Documentation of training and procedures

Quality control results
Laminar airflow hood certification
Production records
Concentration of all preparations
Quality-control documentation is required by various agencies and organizations.
43

Final Exam
Directions: Select the most appropriate answer from the choices given.
1.
Which of the following is not an injectable route of administration?

a.
b.
c.
d.
2.
Sublingual
Intravenous
Intramuscular
Subcutaneous
While the majority of perenteral products are prepared using commercially

available medications and diluents, pharmacy departments still perform
intravenous manufacturing.
a. True
b. False
3.
According to the Scope of Pharmacy Practice Project, ___% of a pharmacy

technicians time is spent collecting, organizing, and evaluating information.
a. 20%
b. 22%
c. 26%
d. 35%
4.
According to the Scope of Pharmacy Practice Project, the second most time
consuming function, ___%, involve preparing, dispensing, distributing, and
administering medications.
a.
b.
c.
d.
5.
35%
21%
24%
18%
Pharmacy technicians must possess which of the following basic requirements

to participate in sterile compounding?
a. A working knowledge of the policy and procedures manual for
compounding, dispensing, and delivering sterile products.
b. Adequate training and adherence to hygienic and aseptic techniques.
c. Knowledge and awareness of the proper methods to store label and
dispose of drugs and supplies.
d. All of the above.
44

Final Exam
6.
The level of difficulty of preparing the compounding prescription is

determined by _________________________________.
a.
b.
c.
d.
7.
The physical properties of the drug being prescribed.

The dosage form desired either by the prescriber or patient.
Both a and b.
Neither a or b.
Sterile compounding is an advanced pharmacy technique that is part of the

general education for a pharmacy technician and does not require additional
training.
a. True
b. False
8.
The pharmacist maintains control over all pharmacy activities and the ultimate
responsibility rest with him or her.
a. True
b. False
9.
The objective of formulating and compounding sterile preparations is:

a. State laws
b. Food and Drug Administration (FDA) regulations
c. Both a and b
d. Neither a or b
10.
Adulteration is:
a. When two drugs that are only compatible with another drug are
compounded together.
b. When the methods used in, or the facilities or controls used for
manufacturing, processing, packing, or holding do no conform to current
good manufacturing practice.
c. Expired drugs
d. None of the above.
11.
When formulating and compounding sterile preparations, the technician must

follow:
a. Federal Regulations
b. State laws
c. Professional standards
d. Written procedures
e. All of the above.
45
Final Exam
12.
As a technician, your work must be checked by a licensed pharmacist.

Dispensing pharmacist must inspect and approve or reject all formulas,
calculations, substances, containers, closures, and in-process materials.
a. True
b. False
13.
Technicians who compound batches of parenteral preparations must follow a

master formula sheet to reproduce preparations that meet all purported norms.
a. True
b. False
14.
An ingredient is only considered a component of a compound if it appears in

the final preparation.
a. True
b. False
15.
For parenteral preparations, the most common vehicle is:

a.
b.
c.
d.
16.
Sodium chloride injection 0.9% solution that is sterilized and packaged in a

single-dose container is sold in no larger than ______ml size.
a.
b.
c.
d.
17.
Water
Dextrose
Sodium Chloride
Lactated ringers injection
30ml
100ml
1000ml
1500ml
All of the following are Water-Miscible Solvents except for:

a. Ethyl alcohol
b. Liquid polyethylene glycol
c. Propylene glycol
d. Lactated ringers injection
46
Final Exam
18.
USP specifies that fixed oils must be:

a. Vegetable in origin
b. Odorless
c. Have no rancid taste
19.
Solutes may be active ingredients or added substances.

a. True
b. False
20.
An antimicrobial agent may be effective in one formula of ingredients but not

in another.
a. True
b. False
21.
_____________ stabilize a solution against degradation.

a.
b.
c.
d.
22.
______________ help to prevent oxidation of the component drug.

a.
b.
c.
d.
23.
Solutes
Antimicrobial agents
Buffering agents
Antioxidants
Solutes
Antimicrobial agents
Buffering agents
Antioxidants
_________________ enhance the effectiveness of antioxidants.

a.
b.
c.
d.
Chelating agents
Tonicity agents
Solubilizers
Emulsifiers
47

Final Exam
24.
___________ are used to suspend tiny oil globules in water to create an

emulsion that contains a uniformed concentration of the active drug
throughout the volume of the liquid.
a.
b.
c.
d.
25.
Chelating agents
Tonicity agents
Solubilizers
Emulsifiers
The closure is part of the container.

a. True
b. False
26.
______________ containers permit withdrawal of successive portions of their

contents without changing the strength, quality, or purity of the remaining
portions.
a. Single-dose
b. Multiple-dose
27.
___________ is the most popular material for sterile preparation containers.

a. Glass
b. Plastic
28.
____________ is a parenteral formulation that is injected directly into the

vein.
a.
b.
c.
d.
29.
Intravenous
Intramuscular
Intradermal
Subcutaneous
___________ is a parenteral formulation that is injected into the substance of

the skin.
a.
b.
c.
d.
Intravenous
Intramuscular
Intradermal
Subcutaneous
48

Final Exam
30.
A solution having a pH of 7 is ____________.

a. Acid
b. Alkalinity
c. Neutral
31.
If sterile water for injection is the vehicle in a formulation, the risk of

pyrogens in water is eliminated.
a. True
b. False
32.
Because numerous factors affect the stability of drug molecules, the choice of
packaging is not important.
a. True
b. False
33.
With a Laminar Flow Hood, the orientation of the direction of airflow can be:
a.
b.
c.
d.
34.
___________ cabinets are totally enclosed, vented, and gastight units.

Operations are conducted through attached rubber gloves, and the cabinet is
maintained under negative pressure.
a.
b.
c.
d.
35.
Horizontal
Vertical
Either
Neither
Class II
Class III
Both a and b
None of the above
If a Laminar Flow Hood is turned off, it is recommended to run for at least

___ minutes before using the work surface area in order to replace the room
air with clean filtered air.
a.
b.
c.
d.
10 minutes
20 minutes
30 minutes
40 minutes
49

Final Exam
36.
Laminar Flow Hoods should be inspected and certified every year.

a. True
b. False
37.
The finer the needle, the higher the gauge number will be.
a. True
b. False
38.
In the selection of an appropriate syringe, as a rule the capacity of the syringe

should be the next size smaller than the volume to be measured.
a. True
b. False
39.
All vials should be swabbed with 70% isopropyl alcohol before needle entry
and left to dry. The swabbing is effective because:
a. The alcohol acts as a disinfecting agent.
b. The physical act of swabbing in one direction remove particles from the
vial diaphragm.
c. Both a and b
d. None of the above
40.
Ampuls are closed-system containers, since air or fluid cannot pass freely in
or out of them.
a. True
b. False
41.
Contamination can be caused by the following factors:

a.
b.
c.
d.
42.
Environment
Equipment
Personnel
All of the above
When laminar airflow is accessible to all sides of an object, the zone of

turbulence extends approximately __ times the diameter of that object.
a. 3
b. 5
c. 10
d. 12
50

Final Exam
43.
__________ is the most common means of contaminating a pharmacycompounded sterile preparation.

a.
b.
c.
d.
44.
Air flow
Expired drugs
Touch
Dirt in the clean room
When wearing gloves, there is no longer a need for hand washing.

a. True
b. False
45.
To ensure fluid transfer into the IV bag, a needle longer than inch should be
used.
a. True
b. False
46.
The order in which drugs are added to the solution may be a factor in
compatibility.
a. True
b. False
47.
48.
Drug labeling is required if:

a. The compounded sterile preparation is not administered immediately
b. If it is administered by someone other than the person who prepared the
medication.
c. Both a and b
d. None of the above.
e.
Certain dosage forms do not need the route of administration on the label
because it is implied.
a. True
b. False
51

Final Exam
49.
Controlled-temperature storage areas such as refrigerators and freezers should

be monitored at least:
a.
b.
c.
d.
50.
Daily
Weekly
Monthly
Annually
Each pharmacy should have written procedures covering:

a. Handling and storage
b. Preparing admixtures
c. Labeling
d. All of the above
52

Texas Tech Pharmacy Course Covers Sterile Compounding

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The Texas Tech University HSC- School of Pharmacy is accredited by The Accreditation

Course Administered By:

STERILE COMPOUNDING AND PREPARATIONS

ACPE No. 0096-9999-09-020-H04-T

Release Date: 4/6/2009

$19.00 (to be paid at time of testing)

Average time to Complete:

Approximately Six hours including testing

Six Contact Hours

Answer 70% of question correctly

J&D Educational Services

J&D Educational Services

Overview of Sterile Compounding and the Role of the C.Ph.T.

Sterile Preparation Formulation

Sterile Preparation Facilities and Equipment

Laminar Flow Hoods

Uses for Sterile Compounding

Policies and Procedures for Compounding Sterile Preparations

Labeling Sterile Preparation

Quality Control and Maintaining Integrity

J&D Educational Services

I. Overview of Sterile Compounding and the Role of the C.Ph.T.

Some patients might be allergic to the diluents and preservatives in commercially

A combination therapy that a prescriber desires, but that is not currently

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J&D Educational Services

Pharmacy technicians must possess the following basic requirements to participate in

A working knowledge of the policy and procedure manuals for compounding,

The level of difficulty of preparing the compounding prescriptions is determined by the

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The objective of formulating and compounding sterile preparations is to provide a dosage

J&D Educational Services

Using the oldest stock first and observing expiration dates.

Storing components under the environmental conditions stated in the individual

Observing components for evidence of instability. Although chemical

Observing components for evidence of lack of sterility. The presence of

Dispensing the proper container with the proper closure.

Sterile compounding equipment must be appropriate in design, size, and

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As a technician, your work must be checked by a licensed pharmacist.

Technicians who compound batches of parenteral preparations must follow a master

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Alter solubility and compatibility of other solutes

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Benzyl alcohol (usually 0.9%) is commonly used in injectables. In oleaginous (oily)

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J&D Educational Services

Intravenous (IV) medication is injected directly into the vein

Inhalation medication is inhaled through the mouth

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Parenteral preparations are classified into six general categories:10

Dextrose Injection, USP

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Amino Acid Injection

Patients receiving chemotherapy

Small-Volume Parenteral Solutions

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Vehicles and solutions

A careful choice of components, containers, and closures can minimize particulate

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III. Sterile Preparation Facilities and Equipment