Chapter 15 - Compounding 1: Basics Flashcards
WHAT ARE COMPOUNDED DRUGS?
- Are they FDA approved?
- Can they be commercially available?
- Compounding is the process of combining or altering ingredients to create a medication.
- A traditional compounded drug is prepared by a pharmacist for an individual patient based on a prescription.
- Compounded drugs meet unique needs and are not FDA-approved.
- The dose or formulation cannot be commercially available as a manufactured product.
What are THE DIFFERENT TYPES OF COMPOUNDING?
What determines the type of the compounded drug?
- Compounded drugs are either:
1) Non-sterile
2) Sterile - Both non-sterile and sterile compounded drugs can be further subdivided into two categories:
1) Non-hazardous
2) Hazardous - The formulation of the compounded drug determines if it is non-sterile or sterile; the drug being used determines if the compound is deemed hazardous
(e.g., causes cancer or adverse reproductive effects).
What are some resources for compounding standards?
1) U.S. Pharmacopeia (USP)
2) American Society of Health-System Pharmacists (ASHP)
The USP Chapters related to compounding include:
1)
2)
3)
- -
The USP Chapters related to compounding include:
1) USP 795 (Non-Sterile Compounding)
2) USP 797 (Sterile Compounding)
3) USP 800 (Handling Hazardous Drugs)
They are considered to be minimum acceptable standards for compounding by:
- The Food and Drug Administration (FDA)
- The State boards of pharmacy
- The Joint Commission
Who rely on the American Society of Health-System Pharmacists (ASHP) for detailed guidance on implementing USP standards.
Hospital pharmacists
Why do we use Non-sterile compounding?
■ Prepare a dose or formulation that isn’t commercially available, such as:
o Changing a solid tablet to a liquid for a patient who cannot swallow the tablet
□ Compounding a 10% ointment when only 5% and 15% are available
■ Avoid an excipient (e.g., gluten or red dye)
■ Add a flavor to a medication to make it more palatable (e.g., a cherry-flavored antiviral suspension for a child)
Non-sterile preparations include those administered by:
mouth, via tube, rectally, vaginally, topically, nasally or in the ear.
USP 795 divides non-sterile compounding into three
categories based on:
Complexity
■ Simple: requires (simply) following instructions
(e.g., preparing a product using a compounding kit that has clear step-by-step instructions, or following a USP monograph)
■ Moderate: involves specialized calculations or procedures, or making a preparation that has no established stability data
(e.g., mixing two topical creams when stability data for the mixture is not available)
■ Complex: requires specialized training, equipment, facilities or procedures (e.g., transdermal dosage forms)
What are some PHYSICAL SPACE BASICS?
- The compounding space should be specifically designated for non-sterile compounding.
- Sterile compounds should be prepared in a distinctly separate location.
- Non-sterile compounding can be performed in ambient air (room air), but must be separated from the dispensing part of the pharmacy.
- Adequate space is needed to avoid mix-ups of ingredients, containers and other components.
- The space should include shelving and storage.
- All components, equipment and containers should be stored off the floor.
- The space should be clean and well-lit.
- Heating, ventilation and air conditioning systems must be controlled to avoid drug deterioration.
- There needs to be adequate plumbing and two types of water:
1. Potable (drinkable, such as from the tap), for hand and equipment washing
2. Purified (e.g., distilled), for use in water-containing formulations, and for rinsing equipment and utensils - The sink must be easily accessible to the compounding area, be clean and be emptied of items unrelated to compounding.
- Soap, detergent and a sanitary method of drying hands (e.g., single-use towels) should be available.
Sterile compounding is used to prepare:
- Drugs injected into the blood or administered into certain other body sites must be free of microorganisms (e.g., bacteria, viruses, fungi) and contaminants (e.g., glass shards, precipitates, particles).
Sterile compounding is used to prepare:
■ IV
(e.g., 1 gram of vancomycin taken from a vial and injected into a 250 mL D5W IV bag)
■ IM/ SQ
■ Radiopharmaceuticals (nuclear medicine drugs- Radiotherapy)
■ Eye drops
(e.g., moxifloxacin and prednisolone eye drops)
■ Irrigations (liquid “washes” that go into a body cavity, such as a gentamicin bladder irrigation)
■ Pulmonary inhalations (does not include nasal inhalations)
BSC
Biological Safety Cabinet
Chemo hood (Class II or III for sterile HD, a type of C-PEC)
CACI
Compounding Aseptic Containment lsolator
Glovebox” for HDs, a type of closed-front C-PEC
CAI
Compounding Aseptic Isolator
“Glovebox” for non-HDs, a closed-front sterile hood (PEC)
C-PEC
Containment Primary Engineering Control
Ventilated (negative pressure chemo hood used for HD
C-SCA
Containment Segregated Compounding Area
Ventilated (negative pressure) room used for HDs;
not in a cleanroom suite (air is not ISO-rated)
C-SEC
Containment Secondary Engineering Control
ventilated (negative pressure) buffer room for HDs (room where the C-PEC is located)
CSPs
Compounded Sterile Products
IVs or other drugs that require sterile manipulation
CSTD
Closed system Transfer device
Device preventing escape of HD/ vapors when transferring (e.g.,from a vial to a syringe)
CVE
Containment Ventilated Enclosure
Ventilated “powder hood” for non-sterile products (can be used for HDs if USP800 standards are met)
LAFW
Laminar Airflow Workbench
Type of sterile hood PEC
Parallel air streams
Flows in 1 direction
LVP
Large Volume Parenteral
IV bag or container containing > 100 mL
PEC
Primary Engineering Control
Sterile hood that provide ISO 5 air for compounding
PPE
Personal Protective Equipment
- Garb (e.g., gown, gloves, mask);
- “Don” means to put on,
- “Doff” is to take off
RABS
Restricted Access Barrier System
“Glovebox”/ Closed-front sterile room (includes CAI & CACI)
SCA
Segregated Compounding Area
Designated space that contains ISO 5 hood but is not part of the clean room
SEC
Secondary Engineering Control
ISO 7 buffer room where Sterile room PEC is located
SVP
Small Volume Parenteral
IV bag or container containing s; 100 ml
USP 797 SPACE REQUIREMENTS FOR STERILE COMPOUNDING
AIR QUALITY AND HEPA FILTERS
- What is ISO? What does it determine?
- In sterile hoods, the ISO # should be:
- Particles per cubic meter in this air is:
- For particles to be included in this count, how large should they be?
- The farther away from the PEC, the — the air.
- What is the buffer area? What ISO should it be?
- What is the anteroom? What ISO should it be in the 2 cases?
- The International Standards Organization (ISO) sets the standards for air quality, which is determined by the NUMBER and SIZE of PARTICLES per VOLUME of AIR.
- The lower the particle count, the cleaner the air.
- In critical areas that are closest to exposed sterile drugs and containers [inside the sterile hood (PEC)], the air quality must be at least ISO 5.
- This means that there are no more than 3,520 particles per cubic meter.
- Particles are included in this count if they are 0.5 microns (micrometers) or larger.
- The farther away from the PEC, the dirtier the air.
- The buffer area (the SEC, which contains PECs) must be at least ISO7.
- The anteroom (the room adjacent to the SEC, where hand washing and garbing occurs) must be at least ISO 8 if it opens into a positive-pressure buffer area (non-HD sterile compounding), or at least ISO 7 if it opens into a negative-pressure buffer area (HD sterile compounding).
ISO 5:
- What area should be iso 5?
- Particles / m3?
- Primary engineering control (PEC, called the sterile hood, or isolator, if using a glove box)
- 3520
ISO 6
1) Compounding area
2) Particles / m3
Not applicable (ISO 6 is not used for pharmacy spaces)
35,200 m3
ISO 7
1) Compounding area
2) Particles / m3
Secondary engineering control (SEC, called the buffer room or buffer area)
Anteroom, if it opens into a negative pressure SEC (same ISO# as the SEC)
352,000 m3
ISO 8
1) Compounding area
2) Particles / m3
Anteroom, if it opens into a positive pressure SEC
3,520,000 m3
- What does HEPA stand for?
- What is its function?
- How efficient are HEPA filters (Particles size)?
- Where is the HEPA filter located in vertical airflow biological safety cabinet (BSC) or C-PEC?
- Where is it located in a laminar airflow workbench (LAFW) or PEC?
- What is the filter covered by?
- What is a blower’s function?
- Direct compounding area is:
- What is the first air?
- When should the HEPA filter be recertified
- How much would the ambient room be rated?
- High-efficiency particulate air (HEPA) filters pick up particles when the air runs through the filter.
- HEPA filters are > 99.97% efficient in removing particles as small as 0.3 microns wide or larger, including bacteria, viruses, fungi and dust.
- HEPA filter is at the top of the sterile hood in a:
- Vertical airflow biological safety cabinet (BSC: Chemo hood class II or III for sterile HD) or
- C-PEC (ventilated negative pressure chemo hood for HD)
- HEPA filter is at the back of the sterile hood (horizontal airflow) in a:
- Laminar airflow workbench (LAFW) (Type of sterile hood (PEC) parallel air streams flow in 1 direction) or
- PEC (Sterile hood that provides ISO 5 air)
- The filter is covered by a protective stainless-steel grill.
- A blower pushes the air through the HEPA filter.
- The filter catches contaminants BEFORE the air enters the inside of the PEC.
- Compounding should be done in the cleanest air, which is the air coming directly out of the HEPA filter.
- This is called the direct compounding area (DCA), and the air from the HEPA filter is called the first air
- The HEPA filter must be recertified by a specialist every 6 months and anytime a PEC has been moved.
- Ambient (room) air is not rated; if it were, most room air would be about ISO 9.
- What is the ISO air quality inside the PEC?
- What are The Direct Compounding Area and First Air?
- Where should you keep the injection port of the vial and the syringe while compounding ?
- What are few things you need to be cautious of?
- The PEC provides ISO 5 air quality for sterile
compounding. - The air coming directly out of the HEPA filter is called the first air, which is cleaner than the rest of the air in the sterile hood.
- To prevent contamination of CSPs (Compounded sterile products) during compounding, the injection port of the vial and the syringe needle must be kept in the first air
■ Do not obstruct first air, especially the area where the needle enters the vial or ampule.
■ Do not block airflow from the HEPA filter with hands or supplies.
■ Place items correctly inside the PEC to avoid creating turbulence, which can lead to contamination of the CSPs.
ISO air quality inside the PEC - Prevent Contamination by Keeping the Air in the PEC Clean:
- With what should you wipe off the outside of all materials before bringing them into the PEC
- Why should you not rip open packages or punch with needles?
- How deep inside the hood should you compound?
- What should you do with the waste?
Prevent Contamination by Keeping the Air in the PEC Clean
■ Wipe off the outside of all materials (vials, syringes) with 70% isopropyl alcohol (IPA) before bringing them into the PEC.
■ Open packages along the designated tear line, if present; do not rip open packages or punch needles or syringes through the wrappers which contaminates the air with particles.
■ Compound at least 6 inches inside the sterile hood to prevent exposing CSPs to dirtier ISO 7 air from the SEC.
■ Move waste out of the PEC shortly after it is created; do not let it accumulate inside the sterile hood.
Air Pressure:
- Positive
- Negative
- In addition to the ISO air quality in a space, the air pressure in the space relative to the adjacent space is important.
- There must be a differential (difference) in air pressure between spaces to keep the air inside a space enclosed, or conversely, to permit the air to enter adjacent areas.
- For non-hazardous compounding, the air pressure inside the PEC and SEC are both positive since the air will not cause toxicity if it moves into adjacent spaces.
- Positive air pressure helps protect the compounded sterile products (CSPs) from contamination.
- With hazardous compounding, the containment PEC (C-PEC) and the containment SEC (C-SEC) must have negative pressure to contain and exhaust the toxic air in the space.
- Negative air pressure protects the compounding staff.
Physical Space Basics:
- Surfaces must be:
- Equipments are usually of which material?
- Can you use cardboard in cleanroom?
- Surfaces of ceilings, walls, floors, fixtures, shelving, counters and cabinets must be smooth, impervious, and free from cracks and crevices to make them easy to clean and disinfect.
- Stainless steel equipment is often used.
- Objects that shed particles (e.g., cardboard boxes) should not be brought into the cleanroom.
What are the 2 TYPES OF STERILE COMPOUNDING AREAS?
■ Cleanroom suite: one or more sterile hoods (ISO 5 PECs) inside an ISO 7 buffer room (SEC) that is entered through an adjacent anteroom.
■ Segregated compounding area (SCA) with an ISO 5 PEC:
- A sterile hood,
- Often an isolator (glovebox) with a closed front,
- Located in a segregated space with unclassified air.
PRIMARY ENGINEERING CONTROL
- The PEC is a device or room that provides an ISO 5 environment for sterile compounding.
- In a pharmacy, the most common way to achieve ISO 5 air is by using a sterile hood.
- In other industries, whole rooms may have ISO 5 air.
PECs for Non-Hazardous Sterile Preparations
- What type of air and pressure are used? Are they externally ventilated?
- What is a LAFW? How does air flow in it?
- What is a CAI? Where can it be located?
- Whats the grab required when compounding in a CAI?
- PECs used for non-hazardous sterile compounding have HEPA-filtered air and positive air pressure, to protect the CSPs from contamination, and are not externally ventilated.
■ A laminar airflow workbench (LAFW) is an open-front PEC where air flows out in parallel lines from the HEPA filter, typically from the back of the hood,
i.e., horizontal laminar airflow (see image).
- Laminar airflow keeps the cleaner air in the PEC from mixing with the dirtier air in the buffer room and keeps particles from colliding with each other and landing on the DCA surface or CSPs.
■ A compounding aseptic isolator (CAI) is a closed-front PEC that can be located in a buffer room (SEC), but is often located in a segregated compounding area (SCA).
- The closed front keeps the unclassified room air around it from mixing with the clean air inside the PEC.
- It is commonly referred to as a glovebox because the pharmacist or technician inserts their hands through the ports on the front into gloves that reside within the PEC.
- Garb required when compounding in a CAI depends on the manufacturer’s instructions, but minimally hand hygiene must be performed and sterile, powder-free gloves should be used inside the CAI (placed over the long gloves attached to the isolator).
The Anteroom:
- what is it?
- what does it contain?
- what is the line of demarcation?
- The side closest to the — is considered to be the dirty side of the anteroom.
- The side of the anteroom closest to the — the clean side.
- how should the shoe covers be placed?
- where does the hand washing and donning of the gown occur?
- The anteroom (sometimes called the ante-area) connects the rest of the pharmacy to the buffer room (SEC).
- It contains a sink, cabinets and benches to facilitate garbing and preparation for compounding.
- Running down the center of the anteroom is a large visible line called the line of demarcation, which separates the room into clean and dirty sections.
- The side closest to the other areas of the pharmacy is considered to be the dirty side of the anteroom.
- This is where hair and face covers are donned.
- The side of the anteroom closest to the buffer room is considered to be the clean side.
- Shoe covers must be applied one at a time while stepping over the demarcation line, placing the covered shoe on the clean side.
- Hand washing and donning of the gown occur on the clean side of the anteroom.
Compounded Sterile Products when Needed Stat:
- what is the beyond used date of that drug?
- The requirements: protective garb and cleaning the PEC take time.
- In certain circumstances, IV drugs are needed stat (i.e., immediately), with no time for aseptic preparation, such as in an ambulance or during a code blue when quick action is needed to save a life.
- This is emergency use, and because the drug has been prepared for that patient under suboptimal conditions for sterility, the CSP will have a very short beyond- use date (BUD) of 1 hour, after which the drug can no longer be used and must be discarded.
SEGREGATED COMPOUNDING AREA
- When is a SCA installed?
- Define?
- For what CSPs could it be used?
- BUD?
- For what kinds of pharmacies or locations are SCA useful
- What does segregated mean?
- SCAs cannot be located adjacent to:
- An SCA is an option when a cleanroom is not able to be installed.
- It is a designated area with unclassified air, such as a corner of the pharmacy.
- It does not have a buffer area or anteroom, and can only be used for certain (low-risk) CSPs.
- The maximum beyond use date (BUD) for a CSP made in an SCA is 12 hours.
- SCAs are useful for satellite pharmacies that are a distance away from the main pharmacy in a large hospital, for infusion centers, clinics and small hospitals.
- Segregated means kept apart from other areas of the pharmacy to minimize contamination, interruptions and noise.
- SCAs cannot be located adjacent to food preparation, warehouses, construction sites, or unsealed windows/doors near busy areas (e.g., not near the pharmacy pick-up area).
Check The Book for figures
What is the USP chapter for Hazardous drugs?
- Hazardous drugs (HDs) can cause toxicity to the healthcare workers who handle them in any manner, including unloading the drugs in the receiving dock, stocking the shelves, preparing the drugs in the pharmacy, administering the drugs to a patient and obtaining and cleaning up body fluids that contain hazardous drug residues.
- HDs require work spaces, equipment and devices that are designed to reduce exposure of the drug to the staff.
- The standards for handling HDs are set by USP in chapter 800.
