Chapter 15-17: Compounding Flashcards
U.S Pharmacopeia: What are they?
U.S Pharmacopeia (USP) sets standards for compounding (preparation, strength, quality, and purity of human/ animal drugs - including manufactured and compounded drugs). USP 795, 797, and 800 are considered to be minimum acceptable standards for compounding for FDA.
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Notes: Hopsital pharmacist relies on The American Society of Health System Pharm (ASHP) for detailed guidance on implementing USP standards
List the different USP and what they entail
Non-Sterile Compounding
Non-Sterile Compounding is primarily used to:
- prepare dose or formulation that is not commercially available such as: changing a solid tablet to liquid for a patient who cannot swallow, compounding a 10% ointment when only 5% and 15% is available
- Avoid an excipient (d/t sensitivity/ allergies like gluten or red dye)
- Add a flavor
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Often include: meds that are PO, via tube, rectally, vaginally, topically, nasally or ear
Non-Sterile Compounding
USP 795 divides non-sterile compounding into 3 catergories based on complexity:
1. Simple: requires following simple instructions (step-by-step)
2. Moderate: involves specialized calculations or procedures, or making preparation that has no established stability data
3. Complex: required specialized training, equip, facilities or procedures
Non-Sterile Compounding
Non-Sterile Compounding: Physical Space
Compounding space should be specifically designed for non sterile compounding. Non sterile compounding can be done in ambient air/ room air but must be separated from dispensing part.
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Adequate space + shelves needed and all equipement, containers, components must be off the floor. Space should be clean and well lit.
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There needs to be adequate plumbing and two types
of water:
1. Potable (drinkable - from the tap), for hand and equipment washing
2. Purified (e.g., distilled), for use in compounded formulations that include water, and for rinsing equipment and utensils.
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Sink should also be clean and have single use towels (sanitary method to dry hands)
Sterile Compounding
Sterile Compounding
Sterile compounding involves stringent procedures to ensure contamination-free products, particularly crucial for intravenous drugs. Contamination risks include microorganisms and foreign particles.
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Sterile compounding is use to prepare: Injections (IV, IM, SC), eye drops, Irrigations, pulmonary inhalation
USP Terminology
CSPs
compound sterile products (IVs or other drugs that require sterile manipulation)
USP Terminology
SVP
small volume parenteral (IV bags < 100mL)
USP Terminology
LVP
LArge volume parenteral (IV bag > 100mL)
USP Terminology
PEC
Primary engineering control - sterile hood that provides ISO 5 air for sterile compounding
USP Terminology
LAFW
Laminar Airflow Workbench - Type of sterile hood (PEC); parallel air steams flow in one direction
USP Terminology
C-PEC
Containment Primary Engineering Control - ventilated (negative pressure) chemo hood used for HDs
USP Terminology
BSC
Biological safety cabinet - chemo hood (class 2 or 3 for sterile HD)
USP Terminology
SEC
Second Engineering Control - ISO 7 buffer room where the sterile hood (PEC) is located
USP Terminology
C-SEC
Containment Secondary Engineering Control - Ventilated (negative pressure) buffer room for hDs (room where the C-PEC is located)
USP Terminology
SCA
Segregated Compounding Area - designated space that contains an ISO 5 hood but not part of a cleanroom suite (air is not ISO-rated)
USP Terminology
C-SCA
Containment Segregated Compounding Area - ventilated (negative pressure) room used for HDs; not in a cleanroom suite (air is not ISO- rated)
USP Terminology
CAI
Compounding Aseptic Isolator - “Glovebox” for non-HDs, a closed front sterile hood (PEC)
UPS Terminology
CACI
Compounding Aseptic Containment Isolator - Glovebox for HDs, a type of closed-front C-PEC
UPS Terminology
RABS
Restricted Access Barrier System - Glovebox/ closed front sterile hood (including CAIs and CACIs)
UPS Terminology
CSTD
Closed System Transfer Device - device preventing escape of HD/ vapors when transferring
USP Terminology
CVE
Containment Ventilated Enclosure - ventilated “power hood” for non-sterile products
Sterile Compounding: Air quality and HEPA filters
- Clean air is crucial in the compounding area to minimize contamination risks. International Standards Organization (ISO) establishes air quality standards based on particle count per volume of air. The lower the particle count, the cleaner the air.
- In critical areas like inside sterile hoods, air must meet at least ISO 5, meaning no more than 3,520 particles per cubic meter of air, with particles of 0.5 microns or larger counted.
-Air quality requirements vary depending on proximity to exposed sterile drugs and containers: Inside the Primary Engineering Control (PEC) must be at least ISO 5. Buffer areas containing PECs must be at least ISO 7. The anteroom, where hand washing and garbing occur, must be at least ISO 8 if opening into a positive-pressure buffer area (non-HD sterile compounding), or ISO 7 if opening into a negative-pressure buffer area (HD sterile compounding).
Regular room air, or “ambient” air, is unclassified and not rated by ISO (~ISO 9)
Sterile Compounding
ISO ratings in the different compounding areas and particles/m3
High-efficiency particulate air (HEPA)
High-efficiency particulate air (HEPA) filters effectively capture particles, including bacteria, viruses, fungi, and dust, with an efficiency of over 99.97% for particles as small as 0.3 microns.
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In vertical airflow biological safety cabinets (BSCs) or compounding primary engineering controls (C-PECs) the HEPA filter is positioned at the top, while in laminar airflow workbenches (LAFWs) or compounding primary engineering controls (PECs), it’s located at the back of sterile hood (horizontal airflow). A blower pushes air through the HEPA filter, trapping contaminants before entering the PEC. Compounding should ideally occur in the area directly receiving air from the HEPA filter, known as the direct compounding area (DCA), where the air is termed “first air.” HEPA filters require recertification every six months and whenever a PEC is relocated.
The dots in the image below show the relevant amount of particles in the air. Ambient (room) air is not rated; if it were, most room air would be about ISO 9 (look at pic)
Sterile Compounding
Air Pressure: What part requires negative vs positive pressure
Apart from maintaining ISO air quality standards, ensuring appropriate air pressure differentials between spaces is crucial. Differentials regulate air movement, either containing it within a space or allowing it to flow into adjacent areas. Positive air pressure is suitable for non-hazardous compounding areas like PECs and SECs, preventing contamination without toxicity concerns. However, for hazardous compounding, containment areas like C-PECs and C-SECs require negative pressure to confine toxic air. Non-sterile hazardous compounding in non-ISO-rated spaces necessitates negative air pressure rooms.
Types of Sterile Compounding Areas
- Cleanroom suite: one or more sterile hood (ISO 5 PECs) inside an ISO 7 Buffer Room (SEC) that is entered thru 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
PECs for Non-Hazardous Sterile Preparations: PECs used for nonhaz compounding have HEPA filtered air and positive air pressure
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Talk about laminar airflow benchwork (LAFW)
It’s an open front PEC where air flows out in parallel lines from HEPA filter, typically from back of hood (ie horizantal laminar airflow). Laminar airflow keeps cleaner air in PEC from mixing with dirty air in buffer room
PECs for Non-Hazardous Sterile Preparations: PECs used for nonhaz compounding have HEPA filtered air and positive air pressure
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Talk about Compounding aseptic isolator (CAI)
it’s a closed front PEC often located in the segregated compounding area (SCA). The clsoed front keeps unclassifed room air from mixng with clean air in the PEC
Sterile Compounding
Talk about Secondary Engineering control
SEC is the room that contains PEC. SEC is sometimes called the buffer area (buffer of relativly clean air of ISO 7 around the PEC which is ISO 5)
Talk about the segregated compounding area
SCA is an option when a cleanroom is not able to be installed. It’s a designed area with unclassified air, such as a corner of that pharmacy. The max BUD for a CPS made in an SCA is 12 hours.
The National Institute for Occupational Safety and Health (NIOSH) determines which drugs are hazardous. A drug is considered haz if it is:
- Carcinogenic
- Teratogenic
- Genotoxic
- Toxic to organ
- labeled by manufactures with special handling instructions
Safety Data Sheets (SDS): Talk about it
Series of safety documents required by OSHA to be accessible to all employees who are working with hazardous materials/ drugs.
Hazard Communication Program: Talk about it
Each facility must have desinated person responsible for creating worker safety procedures for handling hazardous drugs. This include a written plan for implementing safety measures, training, assessing competency, and maintaining documents.
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Pharamcies must maintain a list of all HDs stocked, which should be reviewed annually or when new drugs or doseage forms are introduced.
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Men and women capable of reproduction must provide written confirmation of their understanding of risk of handling HDs
Assessing Risk for Hazardous Drugs (HDs)
USP 797 and USP 800 have different definitions of risk. USP 797 focuses on the risk of contamination of sterile products, while USP 800 considers the risk of harm to workers exposed to hazardous drugs.
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USP 800 has extensive requirements for the safe handling of hazardous drugs, but some activities are considered lower risk, such as counting and packaging tablets. Pharmacies can conduct an Assessment of Risk (AoR) for lower-risk drugs and develop Stand Operating procedures (SOPs) to limit staff exposure. This includes using distinctive shelf bins, wearing appropriate gloves, dedicating counting trays and spatulas, and using sealable bags for prepared hazardous drug containers. If any manipulation of the low-risk hazardous drug is required, full USP 800 requirements must be followed. The AoR documents must be reviewed annually and documented.
When compounding hazardous drugs, both sterile and non-sterile compounds must be prepared in a Containment Primary Engineering Control (C-PEC) that is located in a Containment Secondary Engineering Control (C-SEC) or Containment Secondary Control Area (C-SCA). There are different types of C-PECs available:
- Biological Safety Cabinets (BSCs): These cabinets have vertical laminar airflow that flows down from a HEPA filter at the top of the hood. They provide negative air pressure to protect the worker from exposure to hazardous drugs. Class II or Class III BSCs are required for sterile hazardous drug compounding.
- Containment Ventilated Enclosures (CVEs): These are powder containment hoods with HEPA-filtered air and negative air pressure. They are used for non-sterile compounding only.
- Compounding Aseptic Containment Isolators (CACIs): These closed-front C-PECs, also known as gloveboxes, can be located in a buffer room (C-SEC) but are often placed in a C-SCA.
Non-Sterile and Sterile HD Compounding in the same space
While it’s prefer to keep non sterile and sterile compounding space seperate, exceptions can be made if requirements are met:
- C-SEC must maintain ISO 7
- if there are separate sterile amd non sterile C-PECs in the same C-SEC they must be 1 meter apart
HAZARDOUS DRUG COMPOUNDING
CLEANING SPECIFICS: Sanitization
All areas and equipment handling Hazardous Drugs (HDs) require daily sanitation, involving deactivation, decontamination, and cleaning. Sterile compounding areas and equipment are disinfected last to prevent HD residue spread. Wetted wipes are preferred over spray bottles to avoid aerosolizing HD residue. Workers must wear appropriate PPE, including NIOSH-approved fit-tested respirators when opening containment devices. Commercial kits like Peridox RTU simplify the process, while bleach or peroxide can be used, but bleach may corrode stainless steel surfaces, necessitating neutralization with sodium thiosulfate or other agents. All HD-handling areas (receiving, compounding, administering, disposal) and reusable equipment must undergo routine deactivation, decontamination, and cleaning per USP 800 guidelines, with immediate decontamination required for spills.
Garbing for Hazardous Drugs: just know general stuff
